公开(公告)号：WO2011051922A3

公开(公告)日：2011-11-03

申请号：PCT/IB2010054947

申请日：2010-11-02

申请人： UNIV PADOVA ,  COBELLI CLAUDIO ,  DE NICOLAO GIUSEPPE ,  FACCHINETTI ANDREA ,  GUERRA STEFANIA ,  SPARACINO GIOVANNI

发明人： COBELLI CLAUDIO ,  DE NICOLAO GIUSEPPE ,  FACCHINETTI ANDREA ,  GUERRA STEFANIA ,  SPARACINO GIOVANNI

IPC分类号： G06F19/00 ,  A61B5/1495

CPC分类号： G06F19/3412 ,  A61B5/14532 ,  A61B5/1495 ,  A61B2560/0223 ,  G16H40/40

摘要： In a method of recalibrating continuous glucose monitoring data from a user, operable on a digital processor, an indication from the user that the user has taken a meal is received (806). A self-monitored of blood glucose levels from the user (810) at two separate times during a day corresponding to when the user has taken a meal. A glucose signal is received from a continuous glucose monitoring sensor (818) at times corresponding to the two separate times that the user has taken a meal. Two reconstructed blood glucose values based on the glucose signal from the continuous monitoring sensor at times when the at least two self-monitored of blood glucose levels are received from the user. A linear regression is performed (822) using y = ax + b, wherein x corresponds to the two reconstructed blood glucose values and y corresponds to the two self-monitored of blood glucose levels thereby generating an estimation of a and b. A recalibration signal, including the estimation of a and b, is transmitted to the continuous glucose monitoring sensor (824) based on the linear regression.

摘要翻译： 在可以在数字处理器上操作的用户重新校准连续葡萄糖监测数据的方法中，接收到来自用户已经吃了饭的指示（806）。 在与用户进餐时相对应的一天内的两个不同时间，对使用者（810）的血糖水平进行自我监测。 葡萄糖信号从连续葡萄糖监测传感器（818）接收，时间对应于用户吃饭的两个分开的时间。 在从用户接收至少两次自我监测的血糖水平的时候，基于来自连续监测传感器的葡萄糖信号的两个重建血糖值。 使用y = ax + b进行线性回归（822），其中x对应于两个重建的血糖值，y对应于血糖水平的两个自我监测，从而产生a和b的估计。 基于线性回归，包括a和b的估计的重新校正信号被传送到连续葡萄糖监测传感器（824）。

公开(公告)号：WO2013140423A8

公开(公告)日：2014-01-30

申请号：PCT/IT2012000083

申请日：2012-03-23

申请人： DIPARTIMENTO DI INGEGNERIA CIVILE E ARCHITETTURA DELL UNI DEGLI STUDI DI PAVIA ,  UNIV PADOVA ,  SORU PAOLA ,  MAGNI LALO ,  TOFFANIN CHIARA ,  DE NICOLAO GIUSEPPE ,  DALLA MAN CHIARA ,  COBELLI CLAUDIO

发明人： SORU PAOLA ,  MAGNI LALO ,  TOFFANIN CHIARA ,  DE NICOLAO GIUSEPPE ,  DALLA MAN CHIARA ,  COBELLI CLAUDIO

IPC分类号： G06F19/00

CPC分类号： A61M5/1723 ,  A61M5/14276 ,  A61M2005/14208 ,  A61M2205/04 ,  G06F19/345 ,  G06F19/3456 ,  G06F19/3468 ,  G16H50/20

摘要： Method (400) for controlling the delivery of insulin in a diabetic patient (P) comprising steps of: providing data (d) representative of at least a fraction of a meal ( m(k + i) ) that the patient (P) will consume; providing, from a block (R) representative of conventional therapy or open loop rule that the patient (P) is subject to, based on the data (d) representative of at least a fraction of the foreseen meal (m(k + i) ) that the patient (P) will consume, a reference insulin value (u0); providing data representative of the difference between input data ( y), representative of a reference glycemic level, and feedback data (yCGM) representative of the glycemic level detected in the patient (P); providing, by a control module (301; 401), based on the data representative of the difference between the input data ( y ), representative of the reference glycemic level, and the feedback data (yCGM), representative of the glycemic level detected in the patient (P) and the data (d) representative of at least a fraction of the foreseen meal ( m(k + i) ) that the patient (P) will consume, data (uMPC) representative of a first insulin variation value; providing, based on the data (uMPC), representative of the first insulin variation value, and data (ub), representative of a basal insulin value, a value of insulin (i) to be delivered to the patient (P).

摘要翻译： 用于控制糖尿病患者（P）中胰岛素递送的方法（400），包括以下步骤：提供表示患者（P）将至少一部分膳食（m（k + i））的数据（d） 消耗; 基于表示至少一部分预见餐（m（k + i））的数据（d），从代表患者（P）所接受的常规治疗或开环规则的块（R） ）患者（P）将消耗参考胰岛素值（u0）; 提供表示代表参考血糖水平的输入数据（y）与代表在患者（P）中检测到的血糖水平的反馈数据（yCGM）之间的差异的数据; 通过控制模块（301; 401），基于表示参考血糖水平的输入数据（y）与反馈数据（yCGM）之间的差异的数据提供代表在 表示患者（P）将消耗的至少一部分预见餐（m（k + i））的患者（P）和数据（d）），代表第一胰岛素变化值的数据（uMPC） 提供代表第一胰岛素变化值的数据（uMPC）和代表基础胰岛素值的数据（ub），将被递送给患者（P）的胰岛素（i）的值。

公开(公告)号：WO2013140423A1

公开(公告)日：2013-09-26

申请号：PCT/IT2012/000083

申请日：2012-03-23

申请人： DIPARTIMENTO DI INGEGNERIA CIVILE E ARCHITETTURA DELL'UNIVERSITA' DEGLI STUDI DI PAVIA ,  UNIVERSITA' DEGLI STUDIO DI PADOVA ,  SORU, Paola ,  MAGNI, Lalo ,  TOFFANIN, Chiara ,  DE NICOLAO, Giuseppe ,  DALLA MAN, Chiara ,  COBELLI, Claudio

发明人： SORU, Paola ,  MAGNI, Lalo ,  TOFFANIN, Chiara ,  DE NICOLAO, Giuseppe ,  DALLA MAN, Chiara ,  COBELLI, Claudio

IPC分类号： G06F19/00

CPC分类号： A61M5/1723 ,  A61M5/14276 ,  A61M2005/14208 ,  A61M2205/04 ,  G06F19/00 ,  G06F19/3456 ,  G06F19/3468 ,  G16H50/20

摘要： Method (400) for controlling the delivery of insulin in a diabetic patient (P) comprising steps of: providing data (d) representative of at least a fraction of a meal ( m(k + i) ) that the patient (P) will consume; providing, from a block (R) representative of conventional therapy or open loop rule that the patient (P) is subject to, based on the data (d) representative of at least a fraction of the foreseen meal (m(k + i) ) that the patient (P) will consume, a reference insulin value (u 0 ); providing data representative of the difference between input data ( ŷ ), representative of a reference glycemic level, and feedback data (y CGM ) representative of the glycemic level detected in the patient (P); providing, by a control module (301; 401), based on the data representative of the difference between the input data ( y ), representative of the reference glycemic level, and the feedback data (y CGM ), representative of the glycemic level detected in the patient (P) and the data (d) representative of at least a fraction of the foreseen meal ( m(k + i) ) that the patient (P) will consume, data (u MPC ) representative of a first insulin variation value; providing, based on the data (u MPC ), representative of the first insulin variation value, and data (u b ), representative of a basal insulin value, a value of insulin (i) to be delivered to the patient (P).

摘要翻译： 用于控制糖尿病患者（P）中胰岛素递送的方法（400），包括以下步骤：提供表示患者（P）将至少一部分膳食（m（k + i））的数据（d） 消耗; 基于表示至少一部分预期餐（m（k + i））的数据（d），从代表患者（P）所接受的常规治疗或开环规则的区块（R） ）患者（P）将消耗参考胰岛素值（u0）; 提供表示代表参考血糖水平的输入数据（y）与代表在患者（P）中检测到的血糖水平的反馈数据（yCGM）之间的差异的数据; 基于表示参考血糖水平的输入数据（y）与反馈数据（yCGM）之间的差异的数据，由控制模块（301; 401）提供代表血糖水平检测的血糖水平 表示患者（P）将消耗的至少一部分预见餐（m（k + i））的患者（P）和数据（d）），代表第一胰岛素变化值的数据（uMPC） 基于数据（uMPC）提供代表第一胰岛素变化值的数据，以及代表基础胰岛素值的数据（ub），将被递送给患者（P）的胰岛素（i）的值。

公开(公告)号：WO2011028731A1

公开(公告)日：2011-03-10

申请号：PCT/US2010/047386

申请日：2010-08-31

申请人： UNIVERSITY OF VIRGINIA PATENT FOUNDATION ,  KOVATCHEV, Boris, P. ,  DE NICOLAO, Giuseppe ,  MAGNI, Lalo ,  DALLA MAN, Chiara ,  COBELLI, Claudio

发明人： KOVATCHEV, Boris, P. ,  DE NICOLAO, Giuseppe ,  MAGNI, Lalo ,  DALLA MAN, Chiara ,  COBELLI, Claudio

IPC分类号： A61M31/00

CPC分类号： A61M5/1723 ,  A61B5/14532 ,  A61B5/4839 ,  A61M2230/201 ,  G06F19/00 ,  G06F19/3468 ,  G16H50/50

摘要： A method, system and computer program product for correcting a nominal treatment strategy of a subject with diabetes. The method, system and computer program product may be configured for providing input whereby the input may include: open-loop therapy settings for the subject, data about glycemic state of the subject; and (optionally) data about meals and/or exercise of the subject. The method, system and computer program product may be configured for providing output, whereby the output may include an adjustment (correction) to the open-loop therapy settings for the subject for insulin delivery to the subject.

摘要翻译： 一种用于校正患有糖尿病的受试者的名义治疗策略的方法，系统和计算机程序产品。 方法，系统和计算机程序产品可以被配置用于提供输入，由此输入可以包括：用于对象的开环治疗设置，关于对象的血糖状态的数据; 和（可选）有关膳食和/或运动受试者的数据。 方法，系统和计算机程序产品可以被配置为提供输出，由此输出可以包括针对受试者的胰岛素递送给对象的开环治疗设置的调整（校正）。

公开(公告)号：WO2003079004A2

公开(公告)日：2003-09-25

申请号：PCT/EP2003/002689

申请日：2003-03-14

申请人： PHARMACIA ITALIA S.P.A. ,  UNIVERSITA' DEGLI STUDI DI PAVIA ,  CAMMIA, Cristiano ,  DE NICOLAO, Giuseppe ,  POGGESI, Italo ,  ROCCHETTI, Maurizio

发明人： CAMMIA, Cristiano ,  DE NICOLAO, Giuseppe ,  POGGESI, Italo ,  ROCCHETTI, Maurizio

IPC分类号： G01N33/00

CPC分类号： G06F19/3456 ,  G06F19/00 ,  G06F19/321 ,  G16H50/50

摘要： The present invention relates to a method for estimating or predicting the anti-tumor activity of a compound and for estimating or predicting the tumor growth in mammals; the estimation of the anti-tumor activity of a compound administered to mammals developing a tumor comprises a) measuring the tumor weight in time; b) measuring the concentration of the compound in time; c) calculating, on the basis of said measures, the following kinetic parameters of the tumor growth: a parameter (L 0 ), representative of the portion of the tumor cells present at the instant t 0 =0 that succeeds in taking root and in starting the tumor cells proliferation in the mammals; an index (λ O ) of the production rate of the tumor cells during an exponential phase of the tumor growth; -an index (λ 1 ) of the tumor cells mass produced in the time unit during a linear phase of the tumor growth; and the following pharmacodynamic parameters of the compound: an index (K 1 ) of the tumor cells death rate; an index (K 2 ) of the potency of the compound; and d) calculating, on the basis of said kinetic and pharmacodynamic parameters, tumor growth curves. The invention, applicable in the pharmaceutical field, allows to make the best use of all the information generated during the preclinical studies and results to be sufficiently simple also allowing to get good estimates or predictions regardless of the uncertainties on the mode of action. The invention further allows to employ a small number of parameters, therefore avoiding time consumption as well as a number of mechanistic observations.

摘要翻译： 本发明涉及一种用于估计或预测化合物的抗肿瘤活性并估计或预测哺乳动物肿瘤生长的方法; 估计施用于发展肿瘤的哺乳动物的化合物的抗肿瘤活性包括：a）及时测量肿瘤重量; b）及时测定化合物的浓度; c）根据所述措施，计算肿瘤生长的以下动力学参数：代表在成功获得根的时刻t0 = 0处存在的肿瘤细胞部分的参数（L0），并开始 哺乳动物肿瘤细胞增殖; 肿瘤生长指数期肿瘤细胞产生率的指标（lambdO）; - 在肿瘤生长的线性期间以时间单位产生的肿瘤细胞量的指数（lambd1）; 和化合物的以下药效学参数：肿瘤细胞死亡率的指标（K1）; 该化合物的效力指数（K2）; 和d）根据所述动力学和药效学参数计算肿瘤生长曲线。 适用于制药领域的本发明允许最好地利用在临床前研究期间产生的所有信息，并且结果足够简单，还允许获得良好的估计或预测，而不考虑作用模式的不确定性。 本发明还允许采用少量参数，因此避免了时间消耗以及许多机械观察。

公开(公告)号：WO2011051922A2

公开(公告)日：2011-05-05

申请号：PCT/IB2010/054947

申请日：2010-11-02

申请人： UNIVERSITÀ DEGLI STUDI DI PADOVA ,  COBELLI, Claudio ,  DE NICOLAO, Giuseppe ,  FACCHINETTI, Andrea ,  GUERRA, Stefania ,  SPARACINO, Giovanni

发明人： COBELLI, Claudio ,  DE NICOLAO, Giuseppe ,  FACCHINETTI, Andrea ,  GUERRA, Stefania ,  SPARACINO, Giovanni

IPC分类号： G06F19/00

CPC分类号： G16H40/40 ,  A61B5/14532 ,  A61B5/1495 ,  A61B2560/0223 ,  G06F19/00

摘要： In a method of recalibrating continuous glucose monitoring data from a user, operable on a digital processor, an indication from the user that the user has taken a meal is received (806). A self-monitored of blood glucose levels from the user (810) at two separate times during a day corresponding to when the user has taken a meal. A glucose signal is received from a continuous glucose monitoring sensor (818) at times corresponding to the two separate times that the user has taken a meal. Two reconstructed blood glucose values based on the glucose signal from the continuous monitoring sensor at times when the at least two self-monitored of blood glucose levels are received from the user. A linear regression is performed (822) using y = ax + b, wherein x corresponds to the two reconstructed blood glucose values and y corresponds to the two self-monitored of blood glucose levels thereby generating an estimation of a and b. A recalibration signal, including the estimation of a and b, is transmitted to the continuous glucose monitoring sensor (824) based on the linear regression.

摘要翻译： 在可以在数字处理器上操作的用户重新校准连续葡萄糖监测数据的方法中，接收到来自用户已经吃了饭的指示（806）。 在与用户进餐时相对应的一天内的两个不同时间，对使用者（810）的血糖水平进行自我监测。 葡萄糖信号从连续葡萄糖监测传感器（818）接收，时间对应于用户吃饭的两个分开的时间。 在从用户接收至少两次自我监测的血糖水平的时候，基于来自连续监测传感器的葡萄糖信号的两个重建血糖值。 使用y = ax + b进行线性回归（822），其中x对应于两个重建的血糖值，y对应于血糖水平的两个自我监测，从而产生a和b的估计。 基于线性回归，包括a和b的估计的重新校正信号被传送到连续葡萄糖监测传感器（824）。

公开(公告)号：WO2009059187A1

公开(公告)日：2009-05-07

申请号：PCT/US2008/082063

申请日：2008-10-31

申请人： UNIVERSITY OF VIRGINIA PATENT FOUNDATION ,  MAGNI, Lalo ,  DE NICOLAO, Giuseppe ,  RAIMONDO, Davide Martino ,  COBELLI, Claudio ,  DALLA MAN, Chiara

发明人： MAGNI, Lalo ,  DE NICOLAO, Giuseppe ,  RAIMONDO, Davide Martino ,  COBELLI, Claudio ,  DALLA MAN, Chiara

IPC分类号： A61M5/00

CPC分类号： G06F19/3468 ,  A61B5/14532 ,  A61B5/4839 ,  A61B5/7275 ,  A61M5/1723 ,  A61M2005/14208 ,  A61M2230/201 ,  G06F19/00 ,  G16H50/50

摘要： A system and method for providing optimal insulin injections to a subject, using a controller, a continuous glucose monitor, and an insulin delivery unit is disclosed. The controller possesses a discrete-time, linear model predictive control law, means for sending information to the insulin delivery unit, and means for receiving information from the CGM. The control law implemented is derived from a discrete-time model of glucose insulin dynamics and an aggressiveness parameter. The result is that using only glucose measurements obtained from sensor readings and, prior values of external insulin infusion and meal and exercise announcement the optimal insulin injection necessary to safely regulate blood glucose can be calculated.

摘要翻译： 公开了一种使用控制器，连续葡萄糖监测器和胰岛素递送单元向受试者提供最佳胰岛素注射的系统和方法。 控制器具有离散时间线性模型预测控制规则，用于向胰岛素递送单元发送信息的装置，以及用于从CGM接收信息的装置。 实施的控制规律来自葡萄糖胰岛素动力学的离散时间模型和侵略性参数。 结果是，仅使用从传感器读数获得的葡萄糖测量值，以及外部胰岛素输注和膳食和运动通知的先前值可以计算安全调节血糖所需的最佳胰岛素注射。

公开(公告)号：WO2003079004A3

公开(公告)日：2003-09-25

申请号：PCT/EP2003/002689

申请日：2003-03-14

申请人： PHARMACIA ITALIA S.P.A. ,  UNIVERSITA' DEGLI STUDI DI PAVIA ,  CAMMIA, Cristiano ,  DE NICOLAO, Giuseppe ,  POGGESI, Italo ,  ROCCHETTI, Maurizio

发明人： CAMMIA, Cristiano ,  DE NICOLAO, Giuseppe ,  POGGESI, Italo ,  ROCCHETTI, Maurizio

IPC分类号： G06F19/00

摘要： The present invention relates to a method for estimating or predicting the anti-tumor activity of a compound and for estimating or predicting the tumor growth in mammals; the estimation of the anti-tumor activity of a compound administered to mammals developing a tumor comprises a) measuring the tumor weight in time; b) measuring the concentration of the compound in time; c) calculating, on the basis of said measures, the following kinetic parameters of the tumor growth: a parameter (L 0 ), representative of the portion of the tumor cells present at the instant t 0 =0 that succeeds in taking root and in starting the tumor cells proliferation in the mammals; an index (λ O ) of the production rate of the tumor cells during an exponential phase of the tumor growth; -an index (λ 1 ) of the tumor cells mass produced in the time unit during a linear phase of the tumor growth; and the following pharmacodynamic parameters of the compound: an index (K 1 ) of the tumor cells death rate; an index (K 2 ) of the potency of the compound; and d) calculating, on the basis of said kinetic and pharmacodynamic parameters, tumor growth curves. The invention, applicable in the pharmaceutical field, allows to make the best use of all the information generated during the preclinical studies and results to be sufficiently simple also allowing to get good estimates or predictions regardless of the uncertainties on the mode of action. The invention further allows to employ a small number of parameters, therefore avoiding time consumption as well as a number of mechanistic observations.

公开(公告)号：WO0175639A3

公开(公告)日：2002-10-10

申请号：PCT/EP0103252

申请日：2001-03-22

申请人： PHARMACIA ITALIA SPA ,  BELLAZZI RICCARDO ,  DE NICOLAO GIUSEPPE ,  MAGNI PAOLO ,  POGGESI ITALO ,  ROCCHETTI MAURIZIO

发明人： BELLAZZI RICCARDO ,  DE NICOLAO GIUSEPPE ,  MAGNI PAOLO ,  POGGESI ITALO ,  ROCCHETTI MAURIZIO

IPC分类号： G01N33/15 ,  G05B17/02 ,  G06F17/18 ,  G06F19/00

CPC分类号： G06F19/3456 ,  G05B17/02 ,  G06F19/325 ,  G16H10/20 ,  G16H10/60 ,  G16H50/50

摘要： A method of estimating the average exposure within a population of subjects to a pharmacological substance, administered according to a given protocol, by estimating the area under the concentration curve (AUC), characterised in that the area under the population concentration curve is estimated by the steps of obtaining measurements of the drug concentrations in each of the subjects at any time during the study, independently from the time when measurements of the drug concentration level in the other subjects are being taken; building a hierarchical stochastic model composed of the population and of the individual levels; determining the posterior probability distribution of the average AUC from the sample data and hence the average population AUC. The exposure of an individual and its precision within the sample of individuals can be determined by determining the posterior probability distribution of the individual AUC from the sample data. The posterior probability model may be obtained by using a Markov Chain Monte Carlo algorithm, such as Gibbs Sampling.

摘要翻译： 根据给定方案，通过估计浓度曲线下面积（AUC），估算受试者群体中药物物质平均暴露量的方法，其特征在于，根据群体浓度曲线下的面积由 在研究期间的任何时间获得每个受试者的药物浓度的测量的步骤，独立于其他受试者的药物浓度水平的测量时间; 建立由人口和个人层次组成的分层随机模型; 从样本数据确定平均AUC的后验概率分布，从而确定平均群体AUC。 可以通过从样本数据确定个体AUC的后验概率分布来确定个体的暴露及其在个体样本内的精确度。 后验概率模型可以通过使用马尔科夫链蒙特卡罗算法（例如Gibbs Sampling）获得。