WO2021098892A1

WO2021098892A1 - Device for the preparation of functionalised substances

Info

Publication number: WO2021098892A1
Application number: PCT/CZ2020/000049
Authority: WO
Inventors: Jan Kavalírek; Petr Braťka
Original assignee: Grade Medical s.r.o.
Priority date: 2019-11-23
Filing date: 2020-11-11
Publication date: 2021-05-27
Also published as: CZ2019720A3; EP4061381A1; CZ308630B6

Abstract

A device for the preparation of functionalised substrates, in particular the device for the preparation of functionalised substrates (7) for medical and/or cosmetic use, comprising a modification chamber (1) for applying a modification solution containing nanoparticles and/or micro-particles containing encapsulated active substance onto a carrier substrate (6) by means of a pressure drop between the inlet part (16) and the outlet part (17) of the modification chamber (1), the modification chamber (1) being connected to a module (3) for preparing a modification solution containing at least one active substance.

Description

Device for the preparation of functionalised substrates

Technical Field

The invention relates to a device for functionalising substrates, in particular to a device for the preparation of functionalised substrates for medical and/or cosmetic use.

State of the Art

From the current state of technology, a number of medicinal covering systems with the possibility of drug administration are known, especially in the fields of surgery and dermatology. These systems focus on drug delivery in the form of topical administration with short-term effect or associated systemic administration with possible side effects. Their disadvantage is that they do not allow personalisation of the preparation according to the needs of a particular application.

In further patent documents US4725271, US4122158A and US658222 is described a solution where the active substances are combined with a biodegradable material in such a way that they are incorporated into a mass of biodegradable polymer in the form of fibres, foams or textiles.

In patent documents US60772100, US20020061329 and US5512301 is described a solution in which the active substance is encapsulated in a hydrophilic polymeric mass.

In patent document US20020004063 is described a system where the active substance is applied to a wound. The action of cross-linking initiators solidifies the layer on the patient’s wound and gradually releases the drug.

In another patent document US8715736 is described a system based on lipids with an active substance, where the system is applied directly to the wound to deliver therapeutics directly to the cells by the penetration of stimulating peptides on the surface of the particles. A similar system for scar-free healing is described in W02009061417.

In a further patent document US20090263468 is disclosed a system based on nanoparticles and charge-organised layers for attaching systems to a wound and transporting drugs. A similar system is described in patent document US20100203144.

From the patent document US7972616 is known a composite wound cover based on nanofibres and inorganic particles.

A device for the functionalisation of fibrous structures in medical science is described in patent CZ307805. The device comprises at least one application unit housed in a functionalisation chamber, at least one active substance reservoir, a dosing device and a storage and/or transport holder with a capsule, comprising a carrier, the capsules being for fixation in the device and/or for transport by this device stored in this storage and/or transport holder. The application unit is designed so to be a holder for at least one application hollow needle, with the needle holder and/or the storage and/or transport holder of the capsule with the carrier being adapted to be brought mutually closer to each other, to the extent that the application hollow needle or needles remote from the storage and/or transport holder, the application tip is outside the container and the transport path of the capsule, and in the mutually approximate position the application hollow needle or needles are pushed into the inner space of the capsule by their application tip, above the upper surface or at the surface of the substrate, or furthest below the plane of the unloaded upper surface of the substrate, in a position prior to permanent deformation or damage to the upper surface of the substrate. The disadvantage of this device is that it is relatively slow, but mainly unable to produce a quality functionalised substrate that has a functionally homogeneous structure.

A number of disadvantages are known from the above-mentioned state of current technolgy, the most significant disadvantage being that there is no device which can quickly, efficiently and above all with quality create a functionalised substrate, precisely personalised, all at the point of use.

The object of the invention is to design a device for the preparation of functionalised substrates, which will enable the production of a precisely personalised high-quality functionalised substrate, preferably directly before its being applied to the patient. Principle of the Invention

The above-mentioned disadvantages are largely eliminated and the objects of the invention are fulfilled by a device for the preparation of functionalised substrates, specifically a device for the preparation of functionalised substrates for medical and/or cosmetic use, which according to the invention, is characterised by that it comprises a modification chamber for applying a modifying solution, containing nanoparticles and/or micro-particles containing an encapsulated active substance, onto a carrier substrate by means of a pressure drop between the inlet part and the outlet part of the modification chamber, the modification chamber being connected to a module for preparing a modification solution containing at least one active substance. The modifying solution, containing nanoparticles and/or micro particles containing the encapsulated active substance, can be adsorbed into the carrier substrate wholly or only a part of it can be adsorbed and the excess is discharged from the outlet part of the modification chamber. The great advantage of this device is that it allows simple and rapid production of functionalised substrates in a single device, while in the one device the encapsulation and functionalisation are connected. It is also an advantage that the production of nanoparticles and/or microparticles takes place in one step before the functionalisation of the substrate, which allows the type and concentration of the active substance or more active substances to be adapted exactly to the patient’s needs. This creates the possibility of a completely personalised therapy with full regulation of properties directly by the nursing staff. Depending on the nature of the modification, the individual components may be connected to a system with a variable arrangement and number.

To advantage, the device for preparing the functionalised substrates further comprises at least one source for creating a pressure drop at the inlet and/or outlet of the modification chamber.

It is to further advantage if the module for preparing the modification solution comprises at least one mixing means and at least two containers connected to this. According to a first variant, the means for mixing is a micro-fluidic chip. According to a second variant, the means for mixing is a stirrer. To greatest advantage, the means for mixing the modification fluid is based on creating a turbulent flow within the modification fluid. These especially being turbulences created by mechanical mixers, where passive elements with geometry cause a turbulent flow, and here they are mainly micro-fluidic mixers. Furthermore, it is possible to create turbulence by the action of ultrasonic waves or vibrations, where ultrasonic waves cause a turbulent flow of the fluid. Turbulence can also be created by means of stirrers, where the mechanical element causes a turbulent flow within the liquid by their rotational or eccentric movement. The micro-fluidic chip is to advantage based on a defined mixing of at least 2 liquids due to the precise arrangement of the capillary paths for fluid conduction. The micro-fluidic chip is made of a metal, plastic, ceramic or glass material and the width of the channels can be 10-3000 micrometers. The arrangement of this chip is typically in the form of a T-coupling, X-coupling, coaxial coupling or other morphological modification. The container may advantageously be a dispenser or a storage container.

According to a first variant, the source for creating the pressure drop is a vacuum source arranged in the distribution system behind the modification chamber. In this case, a vacuum is generated in the part of the device for discharging the modifying solution, with a negative pressure drop being created on the support substrate, and the forces thus created cause the modifying solution to flow from the modifying liquid inlet part through the supporting substrate into the modifying solution outlet part.

According to a second variant, the source for creating the pressure drop is a source of overpressure towards the modification chamber arranged in the distribution system in front of the modification chamber. In this case, i.e. in the case of active adhesion by means of overpressure, the pressure of the modifying solution is generated on the side of the device modifying solution inlet. Thus, the modification solution is forced to move through the carrier substrate into the outlet part for the liquid component of the modification solution.

It is further to advantage that the modification chamber comprises a continuous application plate which forms a mechanical support for storage of the carrier substrate.

It is also advantageous if the modification chamber is divided, which allows easy insertion of the carrier substrate and removal of the functionalised substrate.

To advantage, the outlet part of the modification chamber is also connected to the distribution system. Furthermore, it is also advantageous if the modification chamber comprises at least one means for formatting the substrate. Formatting is a physico-chemical change of the parameters of the substrate, for example trimming its edges, and/or its spatial shaping, and/or making perforations to remove a certain shaped part of the substrate, and/or compression over the whole surface, and/or modifying its chemical properties, specifically Ph modification, and/or optional modification to improve the adhesion of immobilised particles.

The main advantage of the invention is that it is possible to quickly and easily prepare a precisely personally functionalised substrate directly at the place of use. In other words, the invention makes it possible to personalise the therapeutic preparation exactly according to the needs of the particular application, hence the precise choice of active substance, excipients and carrier parameters. The patient thus receives precise therapy with a precise distribution of the effect of the active substances over time and their targeted release at the site of application, reducing undesired systemic load with a high localised effect. The advantage is that the primary functionalisation formulation uses a combination of direct formation of nanoparticles and/or micro-particles by liquid techniques and functionalisation of the substrates by immobilisation on the substrate, which is performed primarily by adsorption. Thanks to the encapsulation of active substances into nanoparticles and/or micro-particles, the release kinetics are regulated and their effectiveness is prolonged. Immobilisation of the nanoparticles and/or micro-particles on the substrate ensures their placement at the site of application and prevents them from abruptly flushing out of the desired site of effect. The invention enables the preparation of functionalised preparations, especially for topical medical applications, but also cosmetic or veterinary applications, with the possibility of personalising the carrier by applying different doses of active substance according to the needs of a particular application, or therapy. It is to great advantage that the input of the functionalisation parameters can be performed manually on the device for the preparation of the functionalised substrates by the operating personnel, in the form of the selection of specific parameters or by selecting a preset protocol. Entering functionalisation parameters may include recommendations for their selection, or may also be performed based on automatically transmitted data from another device, such as an IVD diagnostic or skin screening device. Depending on the current settings, the device for the preparation of functionalised substrates can check the suitability of the selected combinations and perform automatic calculations of some parameters depending on the entered parameters. The device for the preparation of functionalised substrates can also be equipped with an interface for machine input of individual input components of the resulting functionalised substrate, for example in the form of a QR code reader or RFID chip reader, where input component packaging information is manually entered at a defined position on the device.

Overview of the Figures

The invention will be further elucidated using drawings, in which fig. 1 shows schematically a device for preparing functionalised substrates for functionalising substrates with three linear dispensers, one stirrer and one micro-fluidic chip, and fig. 2 shows in detail a modification chamber for this device; fig. 3 shows schematically a device for preparing functionalised substrates with two linear dispensers, two storage vessels, one stirrer and one micro-fluidic chip, and fig. 4 shows in detail a modification chamber for this device, and fig. 5 shows schematically a device for preparing functionalised substrates with three linear dispensers and one micro-fluidic chip, and fig. 6 shows in detail a modification chamber for this device.

Examples of the Performance of the Invention

Example 1

The device for preparing functionalised substrates 7 for medical and/or cosmetic use (fig. 1, fig. 2) comprises a modification chamber 1 for applying a modification solution, containing nanoparticles and/or micro-particles containing encapsulated active substance, onto a carrier substrate 6 by means of a pressure drop between the inlet part 16 and the outlet part 17 of the modification chamber 1, the modification chamber 1 being connected to a module 3 for preparing a modification solution containing at least one active substance. The carrier substrate 6 is placed in the modification chamber 1 in a housing 18.

The module 3 for preparing the modification solution comprises two means 4 for mixing and two containers 5 connected to them. The means 4 for mixing are a stirrer 9 and a micro-fluidic chip 8. The containers 5 are two of three linear dispensers 10. The third linear dispenser 10 is connected directly to the modification chamber for dosing excipients.

The device for preparing functionalised substrates 7 further comprises sources 2 for creating a pressure drop at the inlet and outlet of the modification chamber 1 The source 2 for creating a pressure drop in front of the modification chamber are linear dispensers 10. the source 2 for creating a pressure drop, more precisely for creating a vacuum, arranged in the distribution system 13 behind the modification chamber is a vacuum pump.

The modification chamber comprises a continuous application plate 5 for holding the carrier substrate 6.

Both the inlet part 16 and the outlet part 17 and the modification chamber 1 are connected to the distribution system 13. At the end of the distribution system 13, behind the modification chamber 1, a collecting vessel 19 is located.

The device for preparing functionalised substrates 7 further comprises a control unit (not shown).

The device for preparing functionalised substrates 7 allows automated or semi-automated placement of the support substrate housing 18 at the target position in the modification chamber 1 after inserting a correctly oriented housing 18 of carrier substrate into a port (not shown) on the outside of the device.

Example 2

The device for the preparation of functionalised substrates 7 for medical and/or cosmetic use (fig. 3, fig. 4) comprises a modification chamber 1 for applying a modification solution, containing nanoparticles and/or micro-particles containing an encapsulated active substance, onto a carrier substrate 6 by pressure drop between the inlet part 16 and the outlet part 17 of the modification chamber , the modification chamber 1 being connected to a module 3 for preparing a modification solution containing at least one active substance.

The module 3 for preparing the modification solution contains two means 4 for mixing. The means 4 for mixing are a stirrer 9 and a micro-fluidic chip 8. The stirrer 9 is connected to two containers 5, which are two storage containers U. The microfluidic chip 8 is connected to two containers 5, which are two linear dispensers 10.

The device for preparing functionalised substrates 7 further comprises sources 2 for creating a pressure drop at the inlet and outlet of the modification chamber The source 2 for creating a pressure drop in front of the modification chamber 1 are linear dispensers 10 and a peristaltic pump located in the distribution system 3 in front of the stirrer 9.

The source 2 for creating a pressure drop, more precisely for creating a vacuum, arranged in the distribution system 3 behind the modification chamber 1 is a vacuum pump.

The modification chamber 1 comprises a continuous application plate 15 for storing the carrier substrate 6. The modification chamber 1 is divided.

The carrier substrate 6 is inserted into the modification chamber 1 on a handling plate (not shown) after removal from the transport package. The device for the preparation of functionalised substrates 7 also allows operation in a sterile environment, comprising an additional sterilisation (not shown) part of the modification chamber 1, which is a germicidal lamp.

Example 3

The device for preparing functionalised substrates 7 for medical and/or cosmetic use (fig. 5, fig. 6) comprises a modification chamber 1 for applying a modification solution, containing nanoparticles and/or micro-particles containing an encapsulated active substance, onto a carrier substrate 6 by means of a pressure drop between an inlet part 16 and an outlet part 17 of the modification chamber 1, the modification chamber 1 being connected to a module 3 for preparing a modification solution containing at least one active substance.

The module_3 for preparing the modification solution comprises one mixing means 4 and two containers 5 connected to it. The mixing means 4 is a micro-fluidic chip 8. The containers 5 are two of three linear dispensers 10. The third linear dispenser 10 is connected directly to the modification chamber 1 for the dosing of excipients.

The device for preparing functionalised substrates 7 further comprises a source 2 for creating a pressure drop at the inlet to the modification chamber 1. The source 2 for creating a pressure drop in front of the modification chamber 1 are linear dispensers 10. Gravity co-contributes to creating the pressure drop.

The modification chamber comprises a continuous application plate .15 for accommodating the carrier substrate 6. The modification chamber 1 is divided.

The inlet part 6 and the outlet part T7 of the modification chamber are connected to the distribution system 13. At the end of the distribution system 13, behind the modification chamber , a collecting vessel 9 is located.

The modification chamber 1 comprises means for formatting the functionalised substrate 7, which is a cutting tool which, after closing the chamber, makes a shaped cut-out of the functionalised substrate 7 of the desired shape.

Industrial Application

The device for the preparation of functionalised substrates according to the invention can specifically be used for the production of functionalised preparations in the field of materials for medicine, veterinary care and cosmetics.

List of Reference Marks

1 modification chamber

2 source for creating a pressure drop

3 module for preparation of the modification solution

4 means for mixing

5 container

6 carrier substrate

7 functionalised substrate

8 micro-fluidic chip

9 stirrer

10 dispenser

11 storage container

13 distribution system

15 application plate

16 inlet part

17 outlet part

18 housing

19 collecting vessel

Claims

Patent Claims

1. A device for the preparation of functionalised substrates, in particular a device for the preparation of functionalised substrates (7) for medical and/or cosmetic use, characterised by that it comprises a modification chamber (1) for the application of a modification solution, containing nanoparticles and/or micro-particles containing an encapsulated active substance, onto a carrier substrate (6) by means of a pressure drop between the inlet part (16) and the outlet part (17) of the modification chamber (1), the modification chamber (1) being connected to a module (3) for the preparation of a modification solution containing at least one active substance.

2. The device for the preparation of functionalised substrates, according to claim 1 , characterised by that it further comprises at least one source (2) for creating a pressure drop at the inlet and/or outlet of the modification chamber (1).

3. The device for the preparation of functionalised substrates according to any one of the preceding claims, characterised by that the module (3) for the preparation of the modification solution comprises at least one means (4) for mixing and connected to this are at least two containers (5).

4. The device for the preparation of functionalised substrates, according to claim 3, characterised by that the means (4) for mixing is a micro-fluidic chip (8).

5. The device for the preparation of functionalised substrates, according to claim 3, characterised by that the means (4) for mixing is a stirrer (9).

6. The device for the preparation of functionalised substrates according to any one of claims 3 to 5, characterised by that the container (5) is a dispenser (10).

7. The device for the preparation of functionalised substrates according to any one of claims 3 to 5, characterised by that the container (5) is a storage container (11).

8. The device for the preparation of functionalised substrates according to any one of claims 2 to 7, characterised by that the source (2) for generating the pressure drop is a vacuum source arranged in the distribution system (13) behind the modification chamber (1).

9. The device for the preparation of functionalised substrates according to any one of claims 2 to 7, characterised by that the source (2) for creating a pressure drop is a source of overpressure, towards the modification chamber (1) arranged in the distribution system (13) in front of the modification chamber (1).

10. The device for the preparation of functionalised substrates according to any one of the preceding claims, characterised by that the modification chamber (1) comprises a continuous application plate (15) for storing the carrier substrate (6).

11. The device for the preparation of functionalised substrates according to any one of the preceding claims, characterised by that the modification chamber (1) is divided.

12. The device for the preparation of functionalised substrates according to any one of the preceding claims, characterised by that the modification chamber (1) comprises at least one means for formatting the functionalised substrate (7).