Selection of Agents Modulating Gastrointestinal Pain

a technology of gastrointestinal pain and agents, applied in the field of gastrointestinal pain modulation, can solve the problems of complex contraction and relaxation patterns necessary for proper motility of the gastrointestinal tract, accompanied by lower abdominal pain, and distressing infants, parents, involved healthcare professionals, etc., and achieve the effect of reducing or preventing gastrointestinal pain

Inactive Publication Date: 2016-11-17
BIOGAIA AB
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0041]The present embodiments provide an efficient technology that can be used to select or identify agents, in particular bacterial strains, such as Lactic Acid bacteria, that can be used to reduce or prevent gastrointestinal pain in subjects, preferably human subjects, suffering from a disorder or disease causing or is associated with gastrointestinal pain.

Problems solved by technology

The patterns of contraction and relaxation necessary for proper motility of the gastrointestinal (GI) tract are complex and use the nerves and muscles within the GI walls.
This is often also accompanied by lower abdominal pain.
It is distressing for the infant, the parents, and the involved healthcare professionals.
The immaturity of these mechanisms may result in increased vulnerability to feeding intolerance.
Thus, colic may be a common clinical manifestation in the subpopulation of infants who have maturational dysfunction in one or more of the aspects of motility regulation and often leading to GI pain for the infant.
Although TRPV1 is considered to be a potential target for developing drugs to treat different modalities of pain, the widespread expression of the receptor may result in adverse events limiting the use of systemic TRPV1 antagonists in treating gastrointestinal pain.
In particular, antagonizing the receptor could potentially lead to cardiovascular complications as a result of decreased vasoactive peptide release.

Method used

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  • Selection of Agents Modulating Gastrointestinal Pain
  • Selection of Agents Modulating Gastrointestinal Pain
  • Selection of Agents Modulating Gastrointestinal Pain

Examples

Experimental program
Comparison scheme
Effect test

example 1

Mesenteric Nerve Bundle Experiments

Extracellular Recordings

[0166]Adult male Swiss Webster mice (20-30 g) were procured from Charles River Laboratories (Wilmington, Mass.). The mice were killed by cervical dislocation. All ensuing procedures were ex vivo.

[0167]Segments of distal jejunum (˜2.5 cm) with attached mesenteric tissue were removed from freshly killed animals and placed in a Sylgard-coated Petri dish filled with Krebs buffer (in mM): 118 NaCl, 4.8 KCl, 25 NaHCO3, 1.0 NaH2PO4, 1.2 MgSO4, 11.1 glucose, and 2.5 CaCl2 bubbled with carbogen (95% 02-5% CO2). The oral and anal ends of each segment were cannulated with plastic tubing and emptied. The tissue was pinned to the Sylgard, and the mesenteric nerve bundle exposed. The Petri dish was placed onto the stage of an inverted microscope and the lumen gravity perfused at 0.5-1 ml / min with oxygenated Krebs or Krebs with additives (Perez-Burgos A., Wang B et al., American journal of physiology Gastrointestinal and liver physiology 2...

example 2

DSM 17938 Blocked the Ca2+ Rise Induced by Capsaicin in DRG Neuronal Primary Cultures

Dorsal Root Ganglion (DRG) Primary Cultures

[0177]The spinal column was removed from the body, transferred to a beaker containing ice-cold Krebs, and bisected longitudinally. DRG were exposed and collected from the thoracolumbar levels. Whole DRG were washed twice with sterile Leibovitz's L-15 medium (GIBCO, Gaithersburg, Md.), and incubated for 40 min in collagenase type 1 at 1 mg / ml (Sigma-Aldrich; Oakville, ON, Canada) and 0.5 ml trypsin (0.25%, GIBCO) in 20 ml L-15 at 37° C. After further addition of 5 ml L-15 containing 10% fetal bovine serum (FBS, GIBCO), the ganglia were centrifuged for 5 min at 1,000 rpm, then washed twice with growth medium (L-15, containing 10% FBS, 1% Penicillin / Streptomycin / Glutamine, 1% HEPES and 1% Na Pyruvate). The DRG were placed in 2 ml of growth medium and triturated 10 times. The ganglia were then centrifuged for 10 s at 500 rpm and the supernatant transferred to a...

example 3

DSM 17938 Inhibited Heart Rate Slowing Evoked by Gastric Distension

[0180]A total of 17 rats were assigned to 2 groups. Upon arrival, rats were allowed to acclimatize for 1 week followed by handling for 1 week (10 min / d) to minimize stress effects during experiments. Rats were gavaged each morning for 9 d with either 0.2 ml (1×109 cfu / ml) live DSM 17938 in Krebs or only Krebs as control (vehicle). The methods for GD have been previously published (Tougas, Wang, American Journal of Physiology 1999; 277:R272-8). In brief, rats were fasted overnight, anesthetized with a mixture of ketamine hydrochloride (75 mg / kg body weight) and xylazine (10 mg / kg body weight) intraperitoneally. Supplemental anesthesia was given as necessary. After a mid-line laparotomy, a distension device consisting of a ball-shaped gastric balloon (2-cm i.d.) affixed to a Teflon catheter (20 cm) was inserted into the stomach through a small incision in the proximal duodenum and connected to a barostat system (Disten...

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Abstract

The present embodiments relate to selection of agents effective in reducing or preventing gastrointestinal pain in a subject. Such an agent is selected and identified if it is capable of reducing spontaneous and/or induced transient receptor potential vanilloid 1 (TRPV1) activation.

Description

TECHNICAL FIELD[0001]The present invention relates primarily to modulation of gastrointestinal pain and in particular to selection of agents, such as Lactic Acid bacteria, capable of modulating gastrointestinal pain and the use of such agents.BACKGROUND[0002]Gastrointestinal pain is a symptom of many conditions, diseases and disorders associated with the gastrointestinal tract. Functional abdominal pain, refers to recurrent abdominal pain. The vast majority of patients with recurrent abdominal pain have “functional” or “non-organic” pain, meaning that the pain is not caused by physical abnormalities. Various motility disorders are also associated with pain and constipation or diarrhea. The term is used to describe a variety of disorders in which the gut has not developed properly or lost its ability to coordinate muscular activity due to various causes.[0003]Such disorders may manifest in a variety of ways, and includes but are not limited to the following:[0004]Abdominal distention...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/50A61K35/74A61K45/06G01N33/68
CPCG01N33/5041G01N33/6872A61K35/74A61K2035/11G01N2333/705G01N2800/06A61K45/06G01N33/6893A61P1/00A61P43/00G01N33/5008G01N2500/10A61K35/747G01N33/68
Inventor CONOLLY, EAMONNKUNZE, WOLFGANGBIENENSTOCK, JOHN
Owner BIOGAIA AB
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