WO2021107799A1

WO2021107799A1 - Medical device for temporization

Info

Publication number: WO2021107799A1
Application number: PCT/RO2020/000016
Authority: WO
Inventors: Stefan Sorin ARAMA; Daniel Dumitru BANCIU
Original assignee: Arama Stefan Sorin; Banciu Daniel Dumitru
Priority date: 2019-11-27
Filing date: 2020-11-05
Publication date: 2021-06-03
Also published as: RO134455A0

Abstract

The invention named TEMPORISATION MEDICAL DEVICE describes a medical device based on a pharmaceutical formula using the osmotic pressure and pulsatile liposomes for temporisation according to the environment general or specific osmotic factors, with the purpose to perform sampling of substances or release of active substances with a high precision. The temporisation obtained by these means can be precisely regulated according to the estimated osmotic pressures, the pulsatile liposomes dimensions and the specific permeabilities of the semipermeable membranes. The deformations induced by the osmotic pressure occur slowly, according to the pulsatile liposomes characteristics, respectively their diameter, and the osmotic pressure gradient between the environment and the liposomal content.

Description

DESCRIPTION OF THE INVENTION

Title:

Medical Device for Temporization

Technical field:

In-Vivo Medical Devices

Scientific background

The osmotic pressure induces effects through artificial or natural membranes. The pulsatory liposome described by Prof. Dumitru Popescu ( Popescu , Dumitru & Popescu, Alin (2008). The working of a pulsatory liposome. Journal of theoretical biology. 254. 515- 9. 10.1016/j.jtbi.2008.07.009) highlights the ways in which a liposme charged with a hyperosmotic solution in comparisson to the surrounding environment, attracts water inside because of the osmotic pressure, at a certain moment breaks due to the mechanic tension in the membrane, restores the membrane integrity and the process resumes in the new parameters. This is a slow process, due to the slow passing of the water through the wall of the liposome, which consists of a lipidic bilayer.

The necessity of temporisation in the gastrointestinal tract is a desire imposed by the need for controlled release of medication or sampling content at different levels.

One of the current modalities to achieve a temporisation inside the gastrointestinal tract is represented by the gastro-resistant capsule. This usually allows the temporisation of freeing the active substance in the alcaline proximal segments of the small intestine. This approach is currently used in order to protect the drugs which might be altered by the gastric acidity, or to protect the gastric mucosa from drugs which are harmful for the stomach.

Another temporisation method, less used, but described in in-vitro experiments, is represented by the gradual solubilisation process of a wall. Usually, this alternative has a high degree of variability depending to the walls thickness, their purity and the environment in which the walls become soluble.

An already existing temporisation option is the use of an electronic device. Usually, this approach is chosen when it is also necessary to associate other electronic components, such as those necessary to take photos.

Presentation of the technical problem

The technical problem of temporisation can be solved by using a pharmaceutical formula and not using an electronic device, for temporisations according to the local factors.

The description of the invention

The invention relates to a pharmaceutical composition whic allows to temporise actions according to the osmotic pressures. The use of deformable enclosures, such as, but without limitation, those represented by a cylinder containing a piston, allows to obtain an effect which is temporized by the piston movement under the influence of the local factors. A possible local factor is represented by the osmotic pressure in the deformable enclosure, with the piston movement as water is attracted from the environment (for example the gastrointestinal tract). Due to the necessity of controlling this phenomenon as exactly as possible, instead of a homogenous material inside of the deformable enclosure, a suspension of pulsatile liposomes can be used. They can be of different sizes and osmotic concentrations, filled, for instance, with manitol (due to the lack of important adverse events). The use of a semipermeable membrane for water at the entrance in this deformable enclosure, allows the water to move inside the enclosure with high osmotic pressure, and the use of pulsatile liposomes allows a precise temporization of the shape change of the deformable enclosure.

The temporisation device can be used for taking samples from various anatomic areas of the gastrointestinal tract, depending on the temporisation adjustement.

Using of assembled multiple deformable enclosures allows sequential starting or different speed of deformation, according to specific osmotic parameters. For instance, coupling a temporisation device functioning according to the total osmotic pressure of the environment, with a temporisation device functioning according to the total osmotic pressure of the environment minus the osmotic pressure of glucose (made possible by using a supplementary impermeable membrane to glucose) allows a temporised reaction according to the level of glucose in the intestinal lumen. This approach can be used in order to avoid the peaks of high absorbtion of glucose from the intestin, by releasing antiabsorbing factors, without the risk of hipoglycemia, in certain patients (e.g. people desiring to lose weight).

The optional use of identification mechanisms fo the degree of deformation of the enclosure during its intestinal progression could allow the precise identification of the start and the speed of temporisation. In this regard, one can use, for instance, circular pairs of antennas which can modify the resonance behaviour of the enclosure, when evaluated with radiofrequency, according to the relative position of the components.

Benefits of the invention

The temporisation process is correlated with the osmotic pressure, being less dependent to the classic type error factors (e.g. thickness variability or solubilisation speed of a gastro-resistant wall in pills containing slow-release drugs).

The use of temporisation based on a pharmaceutical formula eliminates the risks of adverse reactions due to manufacturing errors or malfunction, by the lack of harmful components. For instance, the accidental release of mannitol can lead, in the worst scenario, to a transient acceleration of the intestinal transit.

Taking samples of material from the gastrointestinal tract, in a controlled manner, would allow a better diagnosis of modifications of the local microbiota, or of various substances, enzymes etc, which would offer an important diagnostic tool for a large array of digestive conditions (dysbiosis induced by antibiotic tratment, irritable bowel syndrome, intestinal inflammatory diseases, malabsorbtion etc).

Temporisation based on total osmotic pressure correlated with glucose osmotic pressure could be useful for controlled release of drugs which decrease the glucose absorbtion. This approach can be used in the weight loss diet or in a better control of diabetes. Detailed presentation of at least one way of manufacturing the device

A gastro-resistant capsule envelopes a cylinder containing a piston (made of biocompatible materials). At one of the ends the cylinder has a semi-permeable membrane for water which allows water to enter without releasing osmotic materials from the inside (e.g. mannitol). Inside the cylinder, next to the semipermeable membrane, there is a high pressure osmotic solution, which contains pulsatile liposomes of different sizes and having a concentration of the osmotic active substance which is similar, in the beginning, to that of the environment in the cylinder and that of the environment in the gastro-resistant capsule. The temporisation is triggered when the gastro-resistant coating is destroyed in the alcaline intestinal environment. As the water is attracted inside the deformable enclosure (cylinder containing the piston, in this case), the piston moves, opening gradually small enclosures of the cylinder. The process of attracting water inside the cylinder goes slowly, in a predictible and programmable manner. Controlling the piston movement according to time will allow taking samples of material from the gastrointestinal tract at different levels or releasing active substances.

Claims

1. The pharmaceutical formula having a capability to temporise actions, characterised by the fact that it is made of deformable enclosures, as it may be but without limiting to, cylinders containing pistons, with active osmotic substances content, which increases its volume by attracting fluid from the environment by means of the osmotic pressure, by using one or more semipermeable membranes for water or for target molecules.

2. The pharmaceutical formula having a capability to temporise actions based on the osmotic pressure, according to claim 1, characterized by the fact that it uses active osmotic solutions which contain pulsatile liposomes of different sizes, according to their behaviour in time, and to the environmental expected osmotic pressure.

3. Medical device with tempohsation capability according to the claims 1 and 2, characterized by the fact that it uses deformation, such as but without limiting to the movement of the piston, for taking sequential samples from interest areas, as there is, but without limiting, the gastrointestinal tract.

4. Medical device with tempohsation capability, according to the claims 1 and 2, characterized by the fact that it uses deformation, as such but without limiting to the movement of the piston, in order to release active substances, in target areas or sequencially.

5. Medical composite device with a capability of tempohsation, according to claims 1 ,

2, 3 and 4, characterized by the fact that it uses deformation, such as but without limiting to the different moves of the pistons according to the correlation between osmotic pressures, for sampling or releasing active substances, such as, but without limiting, in order to diminish the glucose absorbtion to optimal values.

6. Medical composite device with a tempohsation capability, according to claims 1 , 2,

3, 4, and 5, characterized by the fact that it uses deformation, such as but without limiting to the different moves of the pistons according to the correlation between osmotic pressures and predetermined targets, in order to trigger certain modifications meant to allow identification, from outside the organism, of the moment when the tempohsation starts, such as but without limiting to, the coming into proximity of circular antennas with correlated resonance frequency, which allows determining, by radiofrequency with reduced intensity, the tempohsation starting moment and speed of the process.