作者: Bindra, Gurminder ; Mendiratta, Sanjay ; Katoch, Poonam ; Kamal, Charu Mehra ; Anvikar, Anupkumar R ; Pandey, Kritika ; Singh, Sukhwinder ; Chander, Harish

The objective of this current study is to establish a single method for potency and related proteins analysis of human insulin formulations using reverse-phase high performance liquid (RP-HPLC) chromatography technique which was validated and verified for the potency analysis in insulin formulations. Chromatographic separation was achieved using an octadecylsilane (C-18) stationary phase and a mobile phase composed of 55% (v/v) buffer (0.2 M sodium sulfate in water, {pH 2.3}) and 45% (v/v) acetonitrile. Detection was performed by UV detector at 214 nm with a flow rate of 1 ml/min and an injection volume of 20 µL, at 40°C. Currently there are separate methods available in Indian Pharmacopoeia for analysis of Potency and Related proteins in human insulin. We have validated a single method where quantitation of potency and related proteins can be performed in the same run. The method validation exhibited linearity over the concentration range of 0.08-4.5 mg/ml (r²=0.999) with limit of detection of 0.094 mg/ml The accuracy of the method was 99-102.8%. Thus, it is proposed that both potency and related proteins in insulin formulations can be precisely evaluated using a single run thus saving the time and cost for quality analysis of insulin preparations both at manufacturing and regulatory laboratories which in turn will increase the market availability of such standard quality insulin preparations for public health use.

2022-05-01·JAMA pediatrics1区 · 医学

Efficacy and Safety of Enteral Recombinant Human Insulin in Preterm Infants

1区 · 医学

Article

作者: Tagliabue, Paolo ; D’haese, James ; Plaskie, Katleen ; Oddie, Sam ; Giezen, Astrid ; Leah, Leibovitch ; Klinger, Gil ; Ernst, Kimberly D. ; Vento, Máximo ; Mihatsch, Walter A. ; Cornette, Luc M.G.I. ; Couce, Maria L. ; Quesada, Macarena ; Moore, Ryan T. ; Morlacchi, Laura ; Vandeputte, Christine ; Greze, Emily ; Gajda, Anna ; Hascoet, Jean-Michel ; van Toledo, Letty ; Rigourd, Virginie ; Sáenz de Pipáon, Miguel ; Sáenz de Pipaón, Miguel ; Rogers, Theresa J. ; Marks, Kyla ; Atanasova, Victoria G. ; Sonnaert, Michel ; Giuseppi, Agnes ; Shamir, Raanan ; Vento, Giovanni ; Mazille, Nadia ; Agosti, Massimo ; Carnielli, Virgilio P. ; Bellagamba, Maria P. ; Szabó, Hajnalka ; Kooi, Elisabeth M.W. ; Uzunova, Donka P. ; Wardle, Stephen P. ; Cidrás, Manuel ; Lista, Gianluca ; Roggero, Paola ; van Lingen, Richard A. ; Cabrera Lafuente, Marta ; Hubbard, Marie ; Weber, Katrin ; Lapillonne, Alexandre ; Kiss, Judit ; Escribano, Esperanza ; Maton, Pierre ; Shany, Eilon ; Castillo, Felix ; Mandel, Dror ; Troitzky, Mara ; Veskov, Lyuben G. ; Hochwald, Ori ; Biagetti, Chiara ; Schuler, Rahel ; Amato, Orsola ; Szabo, Eva ; Tzipora, Strauss ; Zangen, Shmuel ; Mank, Elise ; Weitkamp, Joern-Hendrik ; Shehadeh, Naim ; Wane, Rachel ; Haham, Alon ; Jubran, Huda ; Tenk, Tamas ; Vervoort, Anne ; del Carmen Sánchez Gómez de Orgaz, María ; Groves, Charlotte ; López-Suárez, Olalla ; Riskin, Arieh ; Nagy, Andrea ; Senterre, Thibault ; Batra, Dushyant ; Rüdiger, Mario ; Beuchée, Alain ; Boyle, Elaine M. ; Malinova, Zornica T. ; Gormaz, María ; Kuehn, Devon ; van Goudoever, Johannes B. ; Jochum, Frank ; Bos, Arend F. ; Costa, Simonetta ; Cools, Filip ; Balázs, Gergely ; Bromiker, Ruben ; Sánchez Luna, Manuel ; Scorrer, Tim

IMPORTANCE:

Feeding intolerance is a common condition among preterm infants owing to immaturity of the gastrointestinal tract. Enteral insulin appears to promote intestinal maturation. The insulin concentration in human milk declines rapidly post partum and insulin is absent in formula; therefore, recombinant human (rh) insulin for enteral administration as a supplement to human milk and formula may reduce feeding intolerance in preterm infants.

OBJECTIVE:

To assess the efficacy and safety of 2 different dosages of rh insulin as a supplement to both human milk and preterm formula.

DESIGN, SETTING, AND PARTICIPANTS:

The FIT-04 multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 46 neonatal intensive care units throughout Europe, Israel, and the US. Preterm infants with a gestational age (GA) of 26 to 32 weeks and a birth weight of 500 g or more were enrolled between October 9, 2016, and April 25, 2018. Data were analyzed in January 2020.

INTERVENTIONS:

Preterm infants were randomly assigned to receive low-dose rh insulin (400-μIU/mL milk), high-dose rh insulin (2000-μIU/mL milk), or placebo for 28 days.

MAIN OUTCOMES AND MEASURES:

The primary outcome was time to achieve full enteral feeding (FEF) defined as an enteral intake of 150 mL/kg per day or more for 3 consecutive days.

RESULTS:

The final intention-to-treat analysis included 303 preterm infants (low-dose group: median [IQR] GA, 29.1 [28.1-30.4] weeks; 65 boys [59%]; median [IQR] birth weight, 1200 [976-1425] g; high-dose group: median [IQR] GA, 29.0 [27.7-30.5] weeks; 52 boys [55%]; median [IQR] birth weight, 1250 [1020-1445] g; placebo group: median [IQR] GA, 28.8 [27.6-30.4] weeks; 54 boys [55%]; median [IQR] birth weight, 1208 [1021-1430] g). The data safety monitoring board advised to discontinue the study early based on interim futility analysis (including the first 225 randomized infants), as the conditional power did not reach the prespecified threshold of 35% for both rh-insulin dosages. The study continued while the data safety monitoring board analyzed and discussed the data. In the final intention-to-treat analysis, the median (IQR) time to achieve FEF was significantly reduced in 94 infants receiving low-dose rh insulin (10.0 [7.0-21.8] days; P = .03) and in 82 infants receiving high-dose rh insulin (10.0 [6.0-15.0] days; P = .001) compared with 85 infants receiving placebo (14.0 [8.0-28.0] days). Compared with placebo, the difference in median (95% CI) time to FEF was 4.0 (1.0-8.0) days for the low-dose group and 4.0 (1.0-7.0) days for the high-dose group. Weight gain rates did not differ significantly between groups. Necrotizing enterocolitis (Bell stage 2 or 3) occurred in 7 of 108 infants (6%) in the low-dose group, 4 of 88 infants (5%) in the high-dose group, and 10 of 97 infants (10%) in the placebo group. None of the infants developed serum insulin antibodies.

CONCLUSIONS AND RELEVANCE:

Results of this randomized clinical trial revealed that enteral administration of 2 different rh-insulin dosages was safe and compared with placebo, significantly reduced time to FEF in preterm infants with a GA of 26 to 32 weeks. These findings support the use of rh insulin as a supplement to human milk and preterm formula.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier: NCT02510560.

2021-09-01·The Israel Medical Association journal : IMAJ4区 · 医学

Efficacy and Safety of Enteral Recombinant Human Insulin for Reduction of Time-to-Full Enteral Feeding in Preterm Infants: A Randomized, Double-blind, Placebo-Controlled Trial.

4区 · 医学

Article

作者: Riskin, Arieh ; Shehadeh, Naim ; Shamir, Raanan ; Simmonds, Aryeh ; Zangen, Samuel

BACKGROUND:

Infants born very prematurely have functionally and structurally immature gastrointestinal tracts.

OBJECTIVES:

To assess the safety and tolerability of administration of enteral recombinant human (rh) insulin on formula fed preterm infants and to assess whether enteral administration of rh-insulin enhances gastrointestinal tract maturation by reducing the time to reach full enteral feeding.

METHODS:

A phase 2, multicenter, double-blind, placebo-controlled, randomized study was conducted. Premature infants (26-33 weeks gestation) were randomized 1:1 to receive insulin 400 μU/ml mixed with enteral feeding or placebo added to their formula. The primary efficacy outcome measure was the number of days required to achieve full enteral feeding. Safety outcomes included adverse events and blood glucose levels.

RESULTS:

The study consisted of 33 infants randomized for the safety population and 31 for efficacy analysis. The mean time to full enteral feeding was 6.37 days (95% confidence interval [95%CI] 4.59-8.15) in the enteral rh-insulin treatment group (n=16) and 8.00 days (95%CI 6.20-9.80) in the placebo group (n=15), which represents a statistically significant reduction of 1.63 days (95%CI 0.29-2.97; P = 0.023). There was no difference in blood glucose levels between the groups and none of the participants experienced hypoglycemia. Adverse events occurred in 9/17 (53%) infants in the enteral rh-insulin group and 12/16 (75%) in the placebo group.

CONCLUSIONS:

Our trial demonstrated that administration of enteral rh-insulin as supplement to enteral nutrition significantly reduced time to achieve full enteral feeding in preterm infants with a gestational age of 26-33 weeks.

100 项与 RH-Insulin (Sunshine Lake) 相关的药物交易

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