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Maturation of mucosal defense and gut/lung function in the preterm infant

A preterm, mucosal technique for the maturation of mucosal defense and gut/lung function in preterm infants

Pending Publication Date: 2020-08-18
NOVOZYMES AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, some reports of probiotic-associated sepsis have raised concerns about the routine clinical use of live bacteria in hosts with immature epithelial barrier defenses, such as premature infants (Patel, 2012)

Method used

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  • Maturation of mucosal defense and gut/lung function in the preterm infant
  • Maturation of mucosal defense and gut/lung function in the preterm infant
  • Maturation of mucosal defense and gut/lung function in the preterm infant

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0323] Example 1. Modulation of gut microbiota by prophylactic treatment with defensins.

[0324] Materials and methods:

[0325] The overall experimental design is as figure 1 The above figure "Preventive Research" shows.

[0326] mouse: Mice were housed in triplicate, 4 cages per group. Feed intake was only registered daily before lights were turned off (at 6pm). Experimental procedures for grouping and cage order changes for individual mice. Mice were maintained at room temperature on a 12-h light / dark cycle under SPF standard conditions.

[0327] diet: For dosing, the average body weight was estimated to be 25 g per mouse. Each mouse eats approximately 3 grams of feed per day.

[0328] treatment solutions: Mice were fed a high-fat diet (HFD) or a low-fat (LF) control diet. HFD contained 4 subgroups; a) hBD-2, b) HD5, c) hBD-2 / HD5 and d) standard HFD without defensin supplementation. The defensin concentration was 1,2 mg hBD-2 per kg mouse per day. HD5 was a...

Embodiment 2

[0336] Example 2. Modulation of gut microbiota by intervention therapy with defensins.

[0337] Materials and methods:

[0338] The overall design of the study is as follows figure 1 The figure below "Treatment Studies" shows.

[0339] mice and diet . Experiments elucidate the role of hBD-2 and HD5 on the microbiota of diet-induced obese mice. The intervention was preceded by a 13-week run-in period in which mice were fed a very HFD (60% energy from fat). Only mice meeting the minimum 12 gram weight gain criterion (approximately 50% of initial body weight) during the run-in period were included in the final analysis. Mice that did not meet these criteria were kept in their respective cages as hierarchical "guardians". It was exposed to all experimental tests but excluded from analysis.

[0340] treatment solutions . Before intervention, MR scans were performed on all mice. Cages of mice were assigned to experimental groups based on their fat mass. All subsequent ...

Embodiment 3

[0350] Example 3. Method to determine the efficacy of prophylactic treatment with oral mammalian α-defensins and β-defensins in a preterm piglet model of necrotizing enterocolitis.

[0351] Materials and methods:

[0352] treatment solutions : 24 premature piglets were delivered by caesarean section at 105 days of gestation. Newborn piglets were immediately transferred to a temperature-regulated and oxygenated incubator. When breathing has stabilized, piglets are placed with umbilical and orogastric catheters. Parenteral nutrition was initially provided to all piglets via an esophageal tube. The enteral formula diet was made from three commercially available products for feeding infants 0-2 years of age.

[0353] Piglets were stratified according to birth weight and sex and divided into control and intervention groups receiving hBD-2.

[0354] test:

[0355] Signs of malaise or weakness (reluctance to stand, cold extremities, distended abdomen, dehydration, pallor, diar...

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Abstract

The present invention relates to methods for maturing the mucosal defense and rebalancing the immune system preventing a cytokine storm; treatment or prevention of neonatal sepsis, necrotizing enterocolitis, acute and prolonged diarrhea, short bowel syndrome, respiratory illness, respiratory infection, respiratory failure, impaired neurodevelopment and extra uterine growth restriction, the methodcomprising oral and / or intrapulmonary and / or subcutaneous administration of at least one antimicrobial peptide selected from the group consisting of Alpha-defensins, Beta-defensins, cathelicidins, lactoferrins / lactoferricins and lysozymes and / or GLP-2 or GLP-2 analogs in a preterm infant or a mother about to give birth to a preterm infant.

Description

technical field [0001] The present invention relates to methods for treating or preventing complications associated with preterm birth, such as sepsis, respiratory disease, necrotizing enterocolitis, short bowel syndrome, impaired neurodevelopment and ectopic growth restriction, which The method is based on the maturation of the gut and lung microbiota and the Normalizes and rebalances the immune system, which reduces the incidence of necrotizing enterocolitis, increases mucosal proportions, increases intestinal villi height and goblet cell density, increases brush border digestive enzyme activity, decreases intestinal hypertrophy Oxidase activity, decreased airway hyperresponsiveness, increased lung compliance, decreased lung inflammation, decreased perivascular and peribronchial inflammation, decreased inflammatory cell counts in bronchoalveolar fluid, and decreased cytokines produce. Background technique [0002] Very low birth weight (ELBW) infants (birth weight < ...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61P1/00A61P11/00A61P1/12
CPCA61K38/1729A61P1/00A61P11/00A61P1/12A61K47/64C07K14/4723A61K9/0043A61K9/0053A61K9/0078A61K45/06C07K2319/31
Inventor P·诺基德
Owner NOVOZYMES AS
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