System, apparatus and method of assembly for administering substances

A kind of material and remote technology, applied in the direction of drug equipment, medical science, surgery, etc., can solve the problems that have not promoted rapid GI tract drug delivery

Active Publication Date: 2022-07-12
MASSACHUSETTS INST OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

No technology yet to facilitate rapid GI tract drug delivery

Method used

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  • System, apparatus and method of assembly for administering substances
  • System, apparatus and method of assembly for administering substances
  • System, apparatus and method of assembly for administering substances

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Example 1: Proof of Concept for Ultrasound for In Vitro Drug Delivery

[0070]To understand whether ultrasound can safely penetrate GI tissue to allow enhanced drug delivery and to determine optimal conditions for UMGID, an in vitro platform was developed using fresh porcine GI tissue mounted in a Franz diffusion cell (see Figure 2A ). The focus was on the use of low frequency (less than 100 kHz) ultrasound in view of previous data showing increased cavitation activity at common intensities compared to high frequency (greater than 1 MHz) ultrasound at the same intensities.

[0071] A. Experimental setup

[0072] Phosphate buffered saline (PBS), hydrocortisone, ammonia salicylic acid, dahlia inulin (5,000 Da) and deuterated dimethyl sulfoxide (DMSO) were obtained from Sigma-Aldrich (Saint Louis, Missouri). Granular D-glucose was obtained from Mallinckrodt Chemicals (Phillipsburg, New Jersey). Lysine labeled with Texas Red was purchased from Invitrogen (Carlsbad, Cali...

Embodiment 2

[0090] Example 2: Characterization of the underlying mechanism of delivery enhancement

[0091] Based on previous studies evaluating phenomena associated with ultrasonic penetration of liquids, the observed enhancement can be attributed to one or more mechanisms including, but not limited to: (1) acoustic fluidization, (2) thermal effects, and (3) ) transient cavitation. To elucidate which mechanisms predominate, tritium was evaluated under the separation effect of stirring the donor chamber (to mimic general stirring that reduces the diffusion boundary layer) and sonication using 1 MHz ultrasound at an intensity below the transient cavitation threshold delivery of glucose to the small intestine to isolate the effects of acoustic fluidization and tissue heating. These protocols were compared to delivery using 20 and 40 kHz ultrasound.

[0092] A. Acoustic Fluidization

[0093] To investigate the effects of acoustic fluidization and agitation, tissue samples were mounted in ...

Embodiment 3

[0134] Example 3: Effects of sonication on the structure and function of therapeutic compounds

[0135] The effect of sonication on the molecular structure of ammonia salicylic acid and hydrocortisone was investigated by analyzing the sonicated molecules with nuclear magnetic resonance (NMR). Deuterated DMSO solutions of ammonia salicylic acid and hydrocortisone were prepared at a concentration of 4 mg / mL. A 1.5 mL sample was sonicated as described above with 20 kHz ultrasound at the highest intensity considered. Three biological parallels were performed. Samples without sonication were used as controls. A Varian 500 (1H, 500 MHz) spectrometer was used to record 1H NMR spectra followed by Mnova NMR software (from Mestralab Research, A Spain) processing. The 1H NMR spectrum (DMSO-d5=2.5 ppm) is quoted in conjunction with the residual non-deuterated solvent offset. All offsets are reported in ppm. The volatile tetramethylsilane (TMS) internal standard was found to disappe...

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Abstract

Substance administration device (2600) includes an elongated body (2606) having a proximal end and a distal end, the elongated body defining an interior chamber (2614) extending between the proximal and distal ends to directing the substance to the distal end, the distal end is connected to a tip (2610) that is at least partially inserted into an orifice in a body cavity of a subject, the tip having a tip configured to be at least partially inserted when the A shape that reduces leakage of the substance from the orifice. the tip includes an opening for delivering the substance from the interior chamber into the body cavity; and transmitting ultrasound from the tip into the body cavity to deliver the substance to tissue in the body cavity of the transducer.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims priority to US Provisional Patent Application No. 62 / 144,842, filed April 8, 2014, and entitled "Systems, Apparatus, and Methods for Administration of Substances," which is incorporated herein by reference in its entirety . technical field [0003] The disclosure relates generally to systems, devices and methods for delivering substances to a subject. More specifically, the disclosure pertains to systems, devices, and methods for ultrasound-mediated gastrointestinal drug delivery. Background technique [0004] The delivery of macromolecules across the gastrointestinal (GI) tract is the most intensively studied area of ​​drug delivery research. However, delivery via the GI tract remains limited to small molecules. Even small molecule delivery presents challenges, as most drugs typically require specialized formulations to stabilize the active pharmaceutical ingredient and provide optimized abso...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61M37/00
CPCA61M31/00A61M37/0092A61M3/0254A61M3/0233A61M3/0275A61M3/0208A61M3/022A61M3/0279A61M2205/123A61M2205/058A61M2210/1067A61M2205/3368A61M2250/00A61M2205/0294A61M2205/0238A61M2210/005A61M2205/586
Inventor C·M·施尔海默C·G·特拉韦尔索A·施罗德B·波拉特D·布朗克舍特恩R·S·朗格W·布鲁格
Owner MASSACHUSETTS INST OF TECH
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