Method and apparatus for removing agglomerates from viscous material

Abstract

A method of filtering or removing agglomerates of individual particles from a viscous material, such as a dermal filler formulation, is provided. The method involves filling the viscous material in an extrusion system that includes a screen or filter placed inside, outside, adjacent or outside the system. The material is forced through the filter / screen, which causes agglomerates present in the viscous material to be filtered / removed due to a large size. Alternatively, pressure-based filtration causes separation of the individual particles, causing the agglomerates to decompose, thereby causing the viscous material to pass through the extrusion system without any clogging issues. The filtered viscous material is suitable for administration to a patient. The invention also describes a device for carrying out the proposed pressure filtration technique.

Description

Technical Field

[0001] The present invention generally relates to filtering agglomerates from viscous injectable materials. More specifically, the present invention relates to methods and devices for removing agglomerates from viscous injectable materials such as dermal fillers. Background Art

[0002] Certain pharmaceutical formulations can be very viscous in nature, which can cause problems when they are administered as an injection. One problem that naturally arises from this densification is the formation of aggregates. These agglomerates create inhomogeneous areas within the hydrogel, sol or colloid, which results in insufficient control of the final injectable material. Viscous materials often have altered rheological properties, which results in poor syringe performance when administered.

[0003] Agglomerates in viscous materials can potentially cause two major problems: blockage and uneven extrusion force. Importantly, agglomerates of individual particles can clog the needle and prevent proper delivery of the drug formulation. Likewise, a partial blockage may require excessive force, which, when cleared, can result in more material being delivered or injected than intended. This can severely impact the end result, as the material will not be delivered as accurately as intended.

[0004] In addition, there are several secondary issues associated with non-uniform particle size distribution. For example, non-uniform materials will have different mechanical properties, which may trigger different immune and host cell responses in the body. For example, a more uniform material could conceivably have more uniform extracellular matrix deposition compared to a single particle agglomerate that limits the surface area for matrix deposition to occur.

[0005] An example of such a viscous material is a dermal filler. Certain viscous materials prepared using powders can be diluted or reconstituted to adjust the viscosity, however, dilution or reconstitution does not work for viscous materials because the problem reappears when the material thickens. For some viscous materials, such as the dermal fillers described by the applicant in international application WO2021 / 248,236, it is desirable to adjust the viscosity of the filler material. For example, low viscosity can enable easier injection, while high viscosity can, for example, maintain uniform particle arrangement and / or can maintain volume for a longer time. Therefore, during the production of dermal fillers, the generated particles must be concentrated to achieve the desired viscosity. In order for such a material to be used as an injectable material, the material must be able to be effectively delivered through a needle or cannula. In addition, certain applications may require certain viscous materials to have a specific particle size or a substantially uniform or controlled particle size distribution. A common solution is to use a large-caliber needle or cannula, however, a large needle can cause pain and inconvenience to the patient. Another common approach to overcome the problems associated with agglomerates is to size and sort the individual particles, however, this can result in a final material with different mechanical properties, which is undesirable.

[0006] Therefore, methods and / or apparatus that can help overcome the above-identified disadvantages are desired. Summary of the invention

[0007] Provided herein is a method for removing agglomerates of individual particles from a viscous material. The method can also be used to filter and size individual particles of a viscous material to achieve uniform mixing of components and a substantially uniform matrix for administration of the viscous material. In one embodiment, the method comprises: removing or filtering agglomerates of individual particles from a viscous material by filling the material in an extrusion system or a first injection device comprising at least one filter / screen. In some embodiments, the extrusion system may include a series of filters / screens. The viscous material is then passed through a filter / screen placed inside, outside, adjacent or outside the extrusion system or the first injection device, which removes or filters the agglomerates, thereby making the viscous material suitable for administration to a patient. The passing step may additionally require forcing the material to pass through the filter / screen under pressure. These methods are suitable for removing / filtering agglomerates of individual particles from a variety of viscous materials including dermal fillers.

[0008] In some examples, the method can be performed differently, wherein the viscous material is first filled or collected in a first collection container. The material is then passed through at least one filter / screen mounted inside the first collection container, and the filtered material is collected in a second collection material, where it is stored before being administered to a patient. The filtered material stored in the second collection container can be transferred to a separate administration / transfer syringe before being administered directly to a patient. Uses of the method for removing / filtering agglomerates and for other purposes are also described.

[0009] A device for removing agglomerates is also provided. A device for removing agglomerates may include an extrusion system or a first injection device, wherein at least one filter / screen is assembled inside the extrusion system. The extrusion system can be optionally connected to a loading container / transfer syringe or a second injection device, which can be used to store filtered viscous material or to administer the material directly to a patient. Different versions of the device are also provided, in which the material is collected in a first collection container having a filter / screen within its body. In some embodiments, the first collection container may include an extrusion system as described above. The first collection container can be optionally connected to a second collection container, which enables the filtered material to be stored in the second collection container before being administered to the patient. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1Results of a needle plugging test using an alkalized viscous material are shown. Figure 1 (A) shows the 27G needle and syringe used for extrusion. Figure 1 (B) shows the extrusion of the alkalized viscous material. Figure 1 (C) Examples of 3D printing or controlled injection / extrusion are provided.

[0011] Figure 2 Shown are the results of a sieving test in which individual particles / agglomerates that were too large to pass through the sieve were collected in a separate container.

[0012] Figure 3 Results of the slippery surface modification test are shown, where the extrusion force profiles for a 0% gelatin formulation (red) and a 5% gelatin formulation (blue) are shown. An extrusion rate of 1 mm / s was used. The material was extruded from a 1 cc syringe through a 27G needle.

[0013] Figure 4 Shown is the mesh employed during the pressure driven screening scheme.

[0014] Figure 5 Shown is a microscope image (10X magnification) of the mesh used during pressure driven sieving.

[0015] Figure 6 Particle size and morphology results investigated / examined after pressure driven sieving are shown. Particles were stained with Congo red and imaged at 10x on a SZ16 stereo microscope (scale = 500 μm).

[0016] Figure 7 Shown is the particle size distribution of a viscous injectable material passing through a mesh in a pressure driven sieving process.

[0017] Figure 8 An inline pressure filtration apparatus of the present invention is shown.

[0018] Fig. 9 An intra-syringe pressure filtration device of the present invention is shown wherein the mesh is placed at the base of the interior portion of the syringe.

[0019] Fig.10 An inline syringe pressure filtration device is shown, where the mesh is housed in a custom Luer lock connector connected between the syringe and the needle.

[0020] Fig.11 A block diagram of the filtration process is shown.

[0021] Fig.12 Block diagrams of small-scale, medium-scale, and large-scale filtration processes are shown. DETAILED DESCRIPTION

[0022] The following description of preferred embodiments is given by way of example only and does not limit the combination of features necessary to implement the invention.

[0023] All terms are intended to be understood as understood by those skilled in the art. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this disclosure belongs. The section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described.

[0024] Although various features of the present disclosure may be described in the context of a single embodiment, these features may also be provided separately or in any suitable combination. Conversely, although the present disclosure may be described herein in the context of separate embodiments for clarity, the present disclosure may also be implemented in a single embodiment.

[0025] The following definitions supplement those in the art and are directed to this application. Therefore, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0026] The terms "first injection device", "extrusion system" and "first collecting vessel" refer to a vessel in which the material to be deagglomerated or filtered is collected prior to the filtering step.

[0027] The terms "second injection device", "loading container", "transfer syringe" or "second collection container" refer to a container that stores the filtered or deagglomerated material after the filtration step or prior to administration to a patient.

[0028] In order to overcome the problems / difficulties associated with the prior art, the inventors have attempted to determine a solution that can limit the number of blockages or completely eliminate blockage events. In addition to removing agglomerates present in viscous materials, the claimed technology also adjusts the size of individual particles of viscous materials without affecting their characteristic features and / or morphology. It is worth noting that, in addition to preventing potential blockage events, having a substantially uniform or controlled extrusion profile is extremely important for the accurate delivery of drug preparations. In order to prevent pressure accumulation and uneven extrusion pressure, the applicant has tested various known techniques and devices to see if any prior art or device can be used to eliminate the problems associated with injecting viscous materials. It is worth noting that the inventors determine and define a blockage event as a needle blockage or a blockage of an extrusion system or a discharge system, wherein the material stops flowing through the needle, i.e., blocking the extrusion system / discharge system. Various embodiments of the present invention are described in detail below.

[0029] Provided herein is a method for removing agglomerates of individual particles from a viscous material for administration to a patient. The method comprises: filling a viscous material in an extrusion system comprising at least one filter / screen; and passing the viscous material through the at least one filter / screen to remove agglomerates of individual particles from the viscous material. The filtered viscous material produced by the method is suitable for administration to a patient.

[0030] In certain embodiments, the method does not alter the characteristic characteristics or morphology of at least 98%, at least 95%, at least 92%, at least 89%, at least 86%, at least 83%, or at least 80% of the individual particles of the viscous material.

[0031] In yet other embodiments, the passing step further comprises forcing the viscous material through at least one filter / screen under pressure / by applying pressure. In certain embodiments, the viscous material is forced through at least one filter / screen by applying pressure using a plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, a roller for a flexible tube, a compressor, or a device capable of adopting a similar mechanism.

[0032] In some embodiments, agglomerates are removed from the viscous material by breaking up / disassembling the agglomerates. Agglomerates are removed from the viscous material by filtering out / sieving out agglomerates that cannot pass through at least one filter / screen.

[0033] In some additional embodiments, the viscous material is pre-filtered through a plurality of pre-filtering devices, wherein the pre-filtering step occurs before the passing step. In some embodiments, the viscous material is pre-filtered through a first pre-filtering device and then through a second pre-filtering device. In some alternative embodiments, the plurality of pre-filtering devices are a series of injection devices, injection-type syringes, an expulsion system, an injection device with a Luer lock connector, a compressible tube, an incompressible tube, a cylinder, or a large syringe.

[0034] In some embodiments, the first pre-filter device and the second pre-filter device are a series of injection devices, injection-type syringes or large syringes, wherein the first pre-filter device has a pore size larger than the second pre-filter device. The pore size of the first pre-filter device and the pore size of the second pre-filter device can be in the range of 18G to 34G.

[0035] In some embodiments, the viscous material is passed through at least one filter / mesh having a pore size / aperture size that is smaller than the individual particle size of the viscous material, and the pore size of the at least one filter / mesh may be in the range of 1 μm to 1000 μm and the individual particle size may be in the range of 20 μm to 1000 μm. In some alternative embodiments, the pore size of the at least one filter / mesh may be in the range of 25 μm to 500 μm and the individual particle size may be in the range of 40 μm to 500 μm. In some other embodiments, the pore size of the at least one filter / mesh may be in the range of 50 μm to 200 μm and the individual particle size may be in the range of 75 μm to 200 μm.

[0036] In some embodiments, the filtered viscous material is collected in a loading container / transfer syringe, wherein the filtered viscous material does not clog the loading container / transfer syringe when injected from the loading container / transfer syringe. In some embodiments, the filtered viscous material achieves a substantially uniform or controlled extrusion profile when injected from the loading container / transfer syringe, and is injected from the loading container / transfer syringe without any pressure buildup after an initial characteristic burst / fracture force.

[0037] In certain embodiments, the individual particles of the viscous material have an intact morphology. The filtered viscous material triggers the desired immune response of the patient after administration. The extrusion system can be an injection-type syringe, an extrusion system, a Luer lock connector device, or a compressible tube. In some embodiments, the extrusion system can be a syringe, wherein the syringe has a needle size in the range of 18G to 34G.

[0038] In some embodiments, wherein the loading container / transfer syringe is an injection-type syringe, an expelling system, a Luer lock connector device, or a compressible tube. In some embodiments, the loading container / transfer syringe can be a syringe, wherein the syringe has a needle size of 18G to 34G. In some of the foregoing embodiments, the volume of the extrusion system is greater than the volume of the loading container / transfer syringe, or wherein the extrusion system has a lower cross-section than the loading container / transfer syringe.

[0039] In some of the foregoing embodiments, at least one filter / screen can be a nylon mesh, a stainless steel mesh, a polytetrafluoroethylene mesh, or a nitrocellulose mesh. At least one filter / screen can be placed inside, outside, adjacent to, or screwed onto the extrusion system, and can be replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer, or a screening channel.

[0040] Notably, the passing step sizes individual particles of the viscous material to produce a substantially uniform or controlled particle matrix for ease of administration. In some embodiments 1, wherein the extrusion system is a Luer lock connector device, wherein at least one filter / screen is assembled / disposed within the Luer lock connector portion of the device.

[0041] The viscous material is forced under pressure / by applying pressure through at least one filter / screen assembled / set in the Luer lock connector portion. Pressure can be applied using a plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, a roller for a flexible tube, a compressor, or a device capable of using a similar mechanism. In some embodiments, pressure is applied using a plunger or an extruder.

[0042] In some embodiments, the passing step can be repeated using multiple filters / screens. In some embodiments, the multiple filters / screens have the same size or different sizes. In some embodiments, the pore size of at least one filter / screen is in the range of 1 μm to 1000 μm.

[0043] In some of the aforementioned embodiments, passing the material through multiple filters / screens reduces the viscosity of the viscous material or adjusts the particle size distribution of the viscous material to a desired level, preferably in the range of 50 μm to 750 μm. The proposed method can also reduce the extrusion force required to inject the viscous material from the extrusion system.

[0044] In certain embodiments, the viscous material is: a dermal filler; a sealant; an adhesive; a composite mixture of mammalian cells; a scaffold material; a bone paste; a bone cement; a cartilage biomaterial; an injectable including a venous stasis application; a protein hydrogel; a carbohydrate hydrogel including cellulose, pectin, and lignin; a cellular material mixture; a thickener; a gelling agent; and a stabilizer.

[0045] Also provided is a method of removing agglomerates of individual particles from a viscous dermal filler material for administration to a patient, the method involving: filling the dermal filler material in an extrusion system including at least one filter / screen; and passing the dermal filler material through the at least one filter / screen such that agglomerates of individual particles are removed from the dermal filler material. The filtered dermal filler material is suitable for administration to a patient.

[0046] In certain embodiments, the method does not alter the characteristic characteristics or morphology of at least 98%, at least 95%, at least 92%, at least 89%, at least 86%, at least 83%, or at least 80% of the individual particles of the dermal filler material.

[0047] In yet other embodiments, the passing step further comprises forcing the dermal filler material through at least one filter / mesh under / by applying pressure.

[0048] In certain embodiments, the dermal filler material is forced through at least one filter / screen by applying pressure using a plunger, extruder, manual compressor, syringe pump, platen compressor, rollers for flexible tubing, compressor, or a device capable of employing a similar mechanism.

[0049] In some embodiments, agglomerates are removed from the dermal filler material by breaking up / disassembling the agglomerates. Agglomerates are removed from the dermal filler material by filtering out / sieving out agglomerates that cannot pass through at least one filter / sieve.

[0050] In some additional embodiments, the dermal filler material is pre-filtered through a plurality of pre-filtering devices, wherein the pre-filtering step occurs before the passing step. In some embodiments, the dermal filler material is pre-filtered through a first pre-filtering device and then through a second pre-filtering device. In some alternative embodiments, the plurality of pre-filtering devices is a series of injection devices, injection-type syringes, drain systems, injection devices with Luer lock connectors, compressible tubing, non-compressible tubing, cylinders, or large syringes.

[0051] In some embodiments, the first pre-filter device and the second pre-filter device are a series of injection devices, injection-type syringes or large syringes, wherein the first pre-filter device has a larger pore size than the second pre-filter device. The pore sizes of the first pre-filter device and the second pre-filter device can be in the range of 18G to 34G.

[0052] In some embodiments, the dermal filler material is passed through at least one filter / mesh having a pore size / aperture size that is smaller than the individual particle size of the dermal filler material, and the pore size of the at least one filter / mesh may be in the range of 1 μm to 1000 μm, and the individual particle size may be in the range of 20 μm to 1000 μm. In some alternative embodiments, the pore size of the at least one filter / mesh may be in the range of 25 μm to 500 μm, and the individual particle size may be in the range of 40 μm to 500 μm. In some other embodiments, the pore size of the at least one filter / mesh may be in the range of 50 μm to 200 μm, and the individual particle size may be in the range of 75 μm to 200 μm.

[0053] In some embodiments, the filtered dermal filler material is collected in a loading container / transfer syringe, wherein the filtered dermal filler material does not clog the loading container / transfer syringe when injected from the loading container / transfer syringe. In some embodiments, the filtered dermal filler material achieves a substantially uniform or controlled extrusion profile when injected from the loading container / transfer syringe, and is injected from the loading container / transfer syringe without any pressure buildup after an initial characteristic burst / break force.

[0054] In certain embodiments, the individual particles of the dermal filler material have an intact morphology. The filtered dermal filler material triggers a desired immune response in the patient after administration. The extrusion system may be an injection-type syringe, an extrusion system, a Luer lock connector device, or a compressible tube. In some embodiments, the extrusion system may be a syringe, wherein the syringe has a needle size in the range of 18G to 34G.

[0055] In some embodiments, the loading container / transfer syringe is an injection-type syringe, an expelling system, a Luer lock connector device, or a compressible tube. In some embodiments, the loading container / transfer syringe can be a syringe, wherein the syringe has a needle size of 18G to 34G. In some of the foregoing embodiments, the volume of the extrusion system is greater than the volume of the loading container / transfer syringe, or wherein the extrusion system has a lower cross-section than the loading container / transfer syringe.

[0056] In some of the foregoing embodiments, at least one filter / screen can be a nylon mesh, a stainless steel mesh, a polytetrafluoroethylene mesh, or a nitrocellulose mesh. At least one filter / screen can be placed inside, outside, adjacent to, or screwed onto the extrusion system, and can be replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer, or a screening channel.

[0057] Notably, the passing step sizes individual particles of the dermal filler material to produce a substantially uniform or controlled particle matrix for ease of administration. In some embodiments 1, wherein the extrusion system is a Luer lock connector device, wherein at least one filter / screen is assembled / disposed within the Luer lock connector portion of the device.

[0058] The dermal filler material is forced under pressure / by applying pressure through at least one filter / screen mounted / disposed within the Luer lock connector portion. The pressure may be applied using a plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, a roller for a flexible tube, a compressor, or a device capable of employing a similar mechanism. In some embodiments, the pressure is applied using a plunger or an extruder.

[0059] In some embodiments, the passing step can be repeated using multiple filters / screens. In some embodiments, the multiple filters / screens have the same size or different sizes. In some embodiments, the pore size of at least one filter / screen is in the range of 1 μm to 1000 μm.

[0060] In some of the aforementioned embodiments, passing the material through multiple filters / screens reduces the viscosity of the dermal filler material or adjusts the particle size distribution of the dermal filler material to a desired level, preferably in the range of 50 μm to 750 μm. The proposed method can also reduce the extrusion force required to inject the dermal filler material from the extrusion system.

[0061] In certain embodiments, the dermal filler material is: a dermal filler; a sealant; an adhesive; a composite mixture of mammalian cells; a scaffold material; a bone paste; a bone cement; a cartilage biomaterial; an injectable including a venous stasis application; a protein hydrogel; a carbohydrate hydrogel including cellulose, pectin, and lignin; a cellular material mixture; a thickener; a gelling agent; and a stabilizer.

[0062] A method for removing agglomerates of individual particles from a viscous material for administration to a patient is provided, the method involving: filling a first collection container including at least one filter / screen with the viscous material; passing the viscous material through the at least one filter / screen so that agglomerates of individual particles are removed from the viscous material; and collecting the viscous material in a second collection container. The filtered viscous material collected in the second collection container is suitable for administration to a patient.

[0063] The first collection vessel comprises an extrusion system, wherein the extrusion system comprises at least one filter / screen. In some embodiments, the method does not alter the characteristic characteristics or morphology of at least 98%, at least 95%, at least 92%, at least 89%, at least 86%, at least 83%, or at least 80% of the individual particles of the viscous material.

[0064] In certain embodiments, the passing step further comprises forcing the viscous material through at least one filter / screen under pressure / by applying pressure. The viscous material can be forced through at least one filter / screen by applying pressure using a plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, a roller for a flexible tube, a compressor, or a device capable of using a similar mechanism.

[0065] In some embodiments, agglomerates are removed from the viscous material by breaking up / disassembling the agglomerates. Agglomerates are removed from the viscous material by filtering out / sieving out agglomerates that cannot pass through at least one filter / screen.

[0066] In some alternative embodiments, the viscous material is pre-filtered by a plurality of pre-filtering devices, wherein the pre-filtering step occurs before the passing step. In some other embodiments, the viscous material is pre-filtered by a first pre-filtering device followed by a second pre-filtering device. The plurality of pre-filtering devices may be selected from a series of injection devices, injection-type syringes, discharge systems, injection devices with Luer lock connectors, compressible tubes, incompressible tubes, cylinders, or large syringes. The plurality of pre-filtering devices may be a series of injection devices, injection-type syringes, or large syringes, wherein the first pre-filtering device has a pore size greater than the second pre-filtering device.

[0067] In some embodiments, the pore size of the first pre-filtering device may be selected from 18G to 34G. In some additional embodiments, the pore size of the second pre-filtering device is selected from 18G to 34G.

[0068] In certain embodiments, the viscous material is passed through at least one filter / sieve having a pore size / aperture size that is smaller than the individual particle size of the viscous material. In some embodiments, the pore size of the at least one filter / sieve may be in the range of 1 μm to 1000 μm, and the individual particle size may be in the range of 20 μm to 1000 μm. In some embodiments, wherein the pore size of the at least one filter / sieve may be in the range of 25 μm to 500 μm, and the individual particle size may be in the range of 40 μm to 500 μm. In some alternative embodiments, the pore size of the at least one filter / sieve is in the range of 50 μm to 200 μm, and the individual particle size is in the range of 75 μm to 200 μm.

[0069] The dispensing device is used to dispense / inject the filtered viscous material which can be collected in a second collection container. In some embodiments, the filtered viscous material does not clog the dispensing device when dispensed / injected from the dispensing device. In some embodiments, the filtered viscous material has a substantially uniform or controlled extrusion profile when dispensed / injected from the dispensing device.

[0070] In some embodiments, the filtered viscous material is dispensed / injected from the dispensing device after the initial characteristic burst / fracture force without any pressure buildup. The individual particles of the viscous material retain their morphology, i.e., have an undamaged morphology. The filtered viscous material is capable of triggering a desired immune response in a patient after administration.

[0071] In some embodiments, the dispensing device can be a series of injection devices, injection-type syringes, discharge systems, injection devices with Luer lock connectors, compressible tubes, non-compressible tubes, cylinders or large syringes. In some other embodiments, the dispensing device is a syringe, wherein the syringe has a needle size of 18G to 34G.

[0072] In some embodiments, at least one filter / screen is a nylon mesh, a stainless steel mesh, a polytetrafluoroethylene mesh, or a nitrocellulose mesh. At least one filter / screen can be placed inside, outside, adjacent to, or screwed onto the first collection container. At least one filter / screen is replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer, or a sieving channel. In some embodiments, the individual particles of the viscous material are sized to produce a substantially uniform or controlled particle matrix for ease of administration.

[0073] In some embodiments, at least one filter / screen is disposed within the Luer lock connector / Luer lock connector portion of the first collection container assembled within the first collection container. Viscous material can be forced under pressure / by applying pressure through at least one filter / screen disposed within the Luer lock connector portion. Pressure can be applied using a plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, a roller for a flexible tube, a compressor, or a device capable of using a similar mechanism. In some alternative embodiments, pressure is applied using a plunger or an extruder.

[0074] In some embodiments, the passing step is repeated using multiple filters / screens, preferably wherein the multiple filters / screens have the same size or have different sizes. The size of at least one filter / screen can be in the range of 1 μm to 1000 μm. In some other embodiments, passing the material through multiple filters / screens reduces the viscosity of the viscous material or adjusts the particle size distribution of the viscous material to a desired level, preferably in the range of 50 μm to 750 μm. In some embodiments, the proposed method reduces the extrusion force required to inject the viscous material from the extrusion system.

[0075] In some embodiments, the viscous material can be: a dermal filler; a sealant; an adhesive; a composite mixture of mammalian cells; a scaffold material; a bone paste; a bone cement; a cartilage biomaterial; an injectable including a venous stasis application; a protein hydrogel; a carbohydrate hydrogel including cellulose, pectin, and lignin; a cellular material mixture; a thickener; a gelling agent; and a stabilizer.

[0076] In certain embodiments, the first collection container is a series of containers with different sizes, a storage unit or chamber, an industrial mixer, an industrial dispenser, an intermediate transfer container, an injection-type syringe, a large injection-type syringe, a Luer lock connector device, a discharge system, or a compressible tube. In some embodiments, the second collection container is selected from at least one of the following: a transfer container, a storage bottle, an injection-type syringe, a filler cartridge, a series of containers with different sizes, a storage unit or chamber, an industrial mixer, an industrial dispenser, an intermediate transfer container, a large injection-type syringe, a Luer lock connector device, a discharge system, or a compressible tube.

[0077] In some further embodiments, the second collection container is used to dispense / inject the filtered viscous material for administration to a patient.The first collection container may have a larger volume than the second collection container.

[0078] Also provided is the use of any of the above method embodiments for reducing the viscosity of a viscous material or a dermal filler material or adjusting the particle size distribution of a viscous material or a dermal filler material to a desired level, preferably in the range of 50 μm to 750 μm. Also provided is the use of any of the above method embodiments for breaking up agglomerates / aggregates in a viscous material or a dermal filler material.

[0079] Further provided is the use of any of the above method embodiments for preventing needle clogging of an injection or dispensing device during delivery of a viscous material or a dermal filler material. Further provided is the use of any of the above method embodiments for sizing individual particles of a viscous material or a dermal filler material such that the viscous material or the dermal filler material has an almost / substantially uniform individual particle size.

[0080] Further provided is the use of any of the above method embodiments for reducing the size of individual particles of a viscous material or a dermal filler material without affecting / impacting the rheological properties of the viscous material or the dermal filler material. Further provided is the use of any of the above method embodiments for reducing the size of individual particles of a viscous material or a dermal filler material without affecting / impacting the rheological properties of the viscous material or the dermal filler material or without affecting / impacting / changing the characteristic features or morphology of individual particles of the viscous material or the dermal filler material.

[0081] Further provided is the use of any of the above method embodiments for filtering a viscous material or a dermal material so that the viscous material or a dermal filler material has a uniform or controlled particle matrix for administration. The viscous material may be selected from the group consisting of a dermal filler; a sealant; an adhesive; a composite mixture of mammalian cells; a scaffold material; a bone paste; a bone cement; a cartilage biomaterial; an injectable including a venous stasis application; a protein hydrogel; a carbohydrate hydrogel including cellulose, pectin and lignin; a cell material mixture; a thickener; a gelling agent; and a stabilizer.

[0082] There is further provided the use of any of the above method embodiments for reducing the individual particle size of a viscous material or a dermal filler material, thereby reducing the extrusion force required to inject the viscous material or the dermal filler material from an extrusion system.

[0083] Further provided is an apparatus for removing agglomerates of individual particles from a viscous material, the apparatus comprising: an extrusion system; and at least one filter / screen placed inside, outside, adjacent to, or screwed onto the extrusion system; wherein, passing the viscous material through the at least one filter / screen removes agglomerates of individual particles from the viscous material.

[0084] In some embodiments, the device further includes an extruder for forcing the viscous material through at least one filter / screen under pressure / by applying pressure. In some embodiments, the extruder pressure can be adjusted by electronic means. At least one filter / screen of the device can be nylon, stainless steel, polytetrafluoroethylene or nitrocellulose. In some embodiments, at least one filter / screen can be a nylon mesh or a stainless steel mesh. In some other embodiments, at least one filter / screen can be replaced by an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer or a screening channel. The size of the inline filter or the screening channel can be in the range of 0.5mm to 2540mm.

[0085] In some embodiments, the extrusion system is connected to a plurality of pre-filtering devices to pre-filter the viscous material before passing the material through at least one filter / screen. The extrusion system can be connected to at least one pre-filtering device and a loading container / transfer syringe, wherein at least one pre-filtering device is connected to the loading container / transfer syringe.

[0086] In some embodiments, the extrusion system is coupled to a loading container / transfer syringe to collect the filtered viscous material. At least one filter / screen may have a pore size smaller than the individual particle size of the viscous material. In some embodiments, at least one filter / screen may have a pore size in the range of 1 μm to 1000 μm, and the individual particle size is in the range of 20 μm to 1000 μm. In some alternative embodiments, at least one filter / screen has a pore size in the range of 25 μm to 500 μm, and the individual particle size is in the range of 40 μm to 500 μm. In some alternative embodiments, at least one filter / screen has a pore size in the range of 50 μm to 200 μm, and the individual particle size is in the range of 75 μm to 200 μm.

[0087] In some embodiments, the extrusion system can be an injection-type syringe, an extrusion system, a Luer lock connector device, or a compressible tube. In some other embodiments, the extrusion system can be a syringe, wherein the syringe has a needle size of 18G to 34G.

[0088] In some embodiments, the loading container / transfer syringe is selected from the group consisting of: an injection-type syringe, an ejection system, a Luer lock connector device, or a compressible tube. In some embodiments, the loading container / transfer syringe can be a syringe, wherein the syringe has a needle size of 18G to 34G.

[0089] In some other embodiments, the volume of the extrusion system is greater than the volume of the loading container / transfer syringe, or wherein the extrusion system has a lower cross-section than the loading container / transfer syringe. In some further embodiments, the extrusion system is a Luer lock connector injection device, wherein at least one filter / screen is disposed within the Luer lock connector.

[0090] A device for removing agglomerates of individual particles from a viscous material is also provided, the device comprising: a first collecting container; at least one filter / screen mounted inside, outside, adjacent to or screwed onto the first collecting container, wherein the viscous material is passed through the at least one filter / screen so that agglomerates of individual particles are removed from the viscous material; and a second collecting container coupled to the first collecting container for collecting the filtered viscous material.

[0091] In some embodiments, the first collection container comprises an extrusion system as described above. The device of claim 169, wherein the first collection container is selected from the group consisting of: a series of containers with different sizes, a storage unit or chamber, an industrial mixer, an industrial dispenser, an intermediate transfer container, an injection syringe, a large injection syringe, a Luer lock connector device, a discharge system, or a compressible tube.

[0092] In some embodiments, the second collection container can be selected from the group consisting of: a transfer container, a storage bottle, an injection syringe, a filler cartridge, a series of containers with different sizes, a storage unit or chamber, an industrial mixer, an industrial dispenser, an intermediate transfer container, a large injection syringe, a Luer lock connector device, a discharge system or a compressible tube. In some other embodiments, an additional filter / screen can be installed in the second collection container. The second collection container can be a collection chamber disposed in the first collection container.

[0093] In certain embodiments, the apparatus further comprises an extruder for forcing the viscous material through at least one filter / screen under / by applying pressure, wherein the extruder pressure is regulated by electronic means.

[0094] In some embodiments, at least one filter / sieve may have a pore size in the range of 1 μm to 1000 μm, and the individual particle size may be in the range of 20 μm to 1000 μm. In some alternative embodiments, at least one filter / sieve has a pore size in the range of 25 μm to 500 μm, and the individual particle size is in the range of 40 μm to 500 μm. In some embodiments, at least one filter / sieve has a pore size in the range of 50 μm to 200 μm, and the individual particle size is in the range of 75 μm to 200 μm.

[0095] In some embodiments, at least one filter / screen can be selected from nylon mesh, stainless steel mesh, polytetrafluoroethylene mesh or nitrocellulose mesh. In some other embodiments, at least one filter / screen can be replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer or a sieving channel.

[0096] In some embodiments, the first collection container may be connected to a plurality of pre-filtering devices to pre-filter the viscous material before passing the viscous material through at least one filter / screen, preferably wherein the first collection container is connected to a plurality of pre-filtering devices and the pre-filtering devices are connected to the second collection container. In some embodiments, the first collection container is connected to a first pre-filtering device and a second pre-filtering device and the pre-filtering device is connected to the second collection container.

[0097] In some embodiments, at least one filter / screen has a pore size that is smaller than a single particle size of the viscous material. In some embodiments, a Luer lock connector can be assembled within the first collection container. In certain embodiments, at least one filter / screen can be placed inside a Luer lock connector assembled within the first collection container.

[0098] The experimental data are discussed in detail below.

[0099] Experimental data

[0100] Experiment A: Blockage Test

[0101] In the occlusion test, the viscous material was allowed to pass through 27G and 30G needles. It was found that while some of the material passed through the needle, periodic occlusions were clearly observed, which is not ideal when injecting / administering viscous drug formulations to patients.

[0102] Figure 1 The needle plugging test results are shown, in which a viscous injectable material was passed through a 27G needle and syringe, as shown in FIG. Figure 1 (A) shown. Figure 1 (B) shows the extruded alkalized viscous material, and Figure 1 (C) An example of 3D printing using controlled injection / extrusion technology is provided. Although some viscous material passed through the needle, periodic blockages made this technology unsuitable for drug delivery applications.

[0103] Conclusion: When the material passed through the 27G needle, 10 mL of material blocked 10 times. When the material passed through the 30G needle, 10.5 mL of material blocked 39 times. As can be clearly seen from the results, both the 27G needle and the 30G needle continued to have periodic plugging and blocking, which means that the blocking test failed.

[0104] Experiment B: Screening Test

[0105] The inventors initially hypothesized that needle clogging was caused by the presence of large individual particles in the viscous injectable material. Therefore, the thick viscous material was diluted so that it could be filtered on a vibrating screen. An attempt was made to pass the material through a large screen and a small screen arranged in series to narrow the particle size distribution. This technique is similar to differential centrifugation, which is known to limit particle size to a desired range. Notably, clogging did not occur initially, however, once the material was concentrated, clogging problems persisted. Figure 2 The results of the sieving test are shown. The figure shows a container in which individual particles / agglomerates that were too large to pass through the 425 μm sieve were collected.

[0106] Screening scheme is described herein.35mL viscous injectable material (such as MerAA or CelluJuve, Ross mixing and extruding sample) is diluted into 1L distilled water, and stirred on a magnetic stirring plate for 15 minutes.The diluted sample is screened by placing a 425μm sieve on the top of the 45μm sieve.500mL diluted sample is transferred to the 425μm sieve, and the vibrator is turned on for 15 seconds.Next, 250mL distilled water is utilized to rinse the 425μm sieve, and the vibrator is turned on for 15 seconds.This step is repeated twice more.The material on the surface of 425μm is discarded.

[0107] Extrusion process: 1 mL of material was loaded into a syringe and a 30G needle was fixed. The material was squeezed out by hand and the number of blockages for each 1 mL group was recorded.

[0108] The following table (Table I) shows the results of the screening test:

[0109]

[0110] Table I. Blockage Counts for Screened Samples

[0111] Conclusion: Sieving tests with set size limits failed to prevent needle clogging. In addition, pressure changes were noted during extrusion. Therefore, sieving alone does not solve the problems mentioned above.

[0112] Experiment C: Hybrid Testing

[0113] Mixing equipment was prepared using interlocking syringes connected to Luer lock adapters. Special mixers (planetary and static) were then used for viscous materials in an attempt to produce a substantially homogeneous material that would not clog the needle.

[0114] Protocol: 1 mL of material was loaded into the syringe again and a 30G needle was fixed. The material was squeezed out manually and the number of blockages for each 1 mL group was recorded. Note that a blockage event was defined as a needle plug, where the material stopped flowing through the needle.

[0115] The following table (Table II) shows the results of the mixed test:

[0116]

[0117]

[0118] Conclusion: It is clear from the table that industrial planetary and static mixers fail to prevent needle clogging.

[0119] Experiment D: Pre-filtration

[0120] A "brute force" method of squeezing the material out was attempted. The viscous material was pushed through the needle until it blocked. After a blocking event, the needle was replaced with a new needle to remove the blockage. The material that successfully passed through the needle was then used for a blockage test with the same size needle used for screening. Periodic blockage of the needle still occurred.

[0121] Conclusion: Prefiltration via extrusion through a targeted needle did not prevent needle clogging.

[0122] Experiment E: Pre-filtration followed by sieving of mixed samples

[0123] Combination of methods was used to remove blockages. Experiments A, B, and C together attempted to evaluate whether additional methods would solve the blockage problem. A sample mixed using an industrial mixer was pre-filtered by extruding the material until the needle blocked, then diluting and sieving to remove any large clumps after replacing the needle with a new one. The material was then collected, loaded into a syringe, and passed through the same size needle used for screening. Blockage events were reduced, but severe blockages still occurred, and the extrusion did not have a very uniform pressure. The results of the combination of methods are provided in Table III below:

[0124]

[0125]

[0126] Table III: Plug counts for material that was extruded then screened.

[0127] Conclusion: Based on the results noted above, the inventors concluded that the combined approach does not provide the necessary solution as it fails to prevent needle clogging.

[0128] Summary Statistics

[0129] In order to evaluate the success of the previous experiments, a statistical summary table was prepared (Table IV). One-way ANOVA showed that the mixed samples (samples from Experiment B) and the mixed pre-filtered / sieved samples (samples from Experiment E) were significantly different (P = 1.2 × 10 -5 ). No significant differences were observed between samples in other experiments at the 0.05 level.

[0130]

[0131] Table IV: Summary statistics for each syringe.

[0132] Conclusion: These results indicate that the methods proposed above are not sufficient to prevent clogging. Clearly, the incidence of clogging is too high. The risks associated with needle clogging extend far beyond changing needles. In addition to product loss during extrusion, needle clogging can also lead to delivery of undesirable amounts of product under the skin, excessive force, and tissue damage.

[0133] Experiment F: Slip surface modification

[0134] It was then hypothesized that the problem of needle clogging and agglomeration could be solved by adding a lubricant to create a slippery surface between particle interfaces. This tribological approach involved mixing a viscous injectable material with different concentrations of gelatin. However, we found that clogging events still occurred and that this approach was unsuccessful in removing agglomerates of individual particles from the viscous sample.

[0135] like Figure 3 As shown, from the repeated extrusion force curves and the sharp increase in force to overload the system (no falling portion of the curve), it is obvious that adding lubricant (gelatin) does not prevent the occurrence of blockage. It is worth noting that these curves show the superimposed force curves of repeated extrusion.

[0136] Conclusion: The addition of lubricants attempted to create a slippery surface between individual particles of the viscous material but failed to eliminate the blockage.

[0137] Experiment G: Pressure-driven screening

[0138] The inventors have designed a solution for breaking up agglomerates without crushing them using carefully selected filters / screens (such as small channels or mesh screens). The method breaks up or disassembles agglomerates by efficiently separating individual particles without affecting their desired rheological properties. The channels and mesh screens can include a variety of different materials and sizes. Although there may be a variety of combinations and prototypes, the original prototype involves passing the material through a 27G to 30G needle for a pre-filtration step. In some embodiments, the pore size of the pre-filtration injection device is in the range of 18G to 34G. After pre-filtration, the material passing through the needle is collected, and then the material is extruded using a needle in the range of 18G to 34G for final extrusion. The needle used in the final extrusion step has a lower gauge size than the needle used in the pre-filtration step. In the dense final form, the material is forced to pass through a filter / screen whose pore size or pore size is smaller than the average size of the individual particles of the material (e.g., a single particle is about To 250 μm, the screen is 75 μm to 150 μm, however, the mesh size can be in the range of 1 μm to 1000 μm depending on the particle size of the viscous material). In some embodiments, the individual particle size can be in the range of 20 μm to 1000 μm. It should be noted that the alkalized individual particles are able to bend and squeeze through the pores without breaking or causing any damage to the morphology of these particles or any effect on the rheological properties of these particles. Surprisingly, the small pore size effectively removes and breaks up the aggregates, thereby confirming the successful removal of agglomerates of individual particles from the viscous material. After small pore filtration (i.e., filtering the material using a filter with a pore size smaller than the individual particles), no needle clogging was found, and a highly uniform extrusion profile was obtained without observable intermittent pressure accumulation and release.

[0139] Protocol: In an exemplary embodiment, the material is preloaded into an injection device or extrusion system (such as a syringe). The syringe is pressed firmly against a filter / screen used as a Falcon tube filter, such as Figure 4 shown. Figure 5 A 10X magnified microscopic image of the mesh used in the exemplary embodiment is shown. The material passed through the syringe was then loaded into a 1cc syringe and finally extruded through needles of different sizes (ranging from 27G to 33G) at a 1mL volume and the number of clogging events was recorded (as shown in Table V below).

[0140]

[0141] Table V. Blockage Counts of Material Passing Through the Mesh

[0142] To analyze the efficacy of the designed process, the inventors performed a one-way ANOVA, which showed that the nylon mesh extrusion samples were significantly different from the industrial mixer samples and the sieved samples, respectively (P = 4 × 10 -8 and P = 0.0126).

[0143] While the occlusion test results were promising, the inventors recognized that it was important to study particle size and morphology to ensure that individual particles were not fragmented or damaged, as this could cause an undesirable immune response in a patient following administration.

[0144] The particles were stained with 0.1% Congo red and imaged on a SZ16 stereomicroscope with a BV filter. Figure 6 Shown, scale is 500 μm. Figure 7The distribution of particle sizes passing through the web is shown. As can be seen from the figure, the individual particles are not damaged and 0.86% of the individual particles are smaller than 20 μm. Analysis of N=1282 individual particles yielded an average particle size of 246.64±2.52 μm (mean±standard error of the mean). However, such a distribution is expected.

[0145] Based on the results provided in Table V, one-way variance analysis and dyeing test, the inventors draw conclusions that passing material through a filter / screen (such as a mesh screen) can fully break up particle agglomerates and prevent blocking from occurring by separating individual particles. When material is extruded by an injection device or an extrusion system (such as a 27G, 30G or 33G needle), no blocking event occurs. Qualitatively, after the characteristic initial burst force, extrusion has a very uniform pressure. In addition, in this experiment, the observations about pressure change and pressure accumulation in the past extrusion experiment are not observed. In fact, no blocking event is recorded, and substantially uniform extrusion is achieved.

[0146] It can be said that the proposed method for filtering and screening individual particles of viscous injectable materials involves combining pressure and screens, rather than using screens or pressure alone. As understood by those skilled in the art, all other "obvious" methods failed to provide the desired extrusion profile. In addition, the initial assumption that high pressure screening only "forces" large agglomerates through the net and provides a filler material that shows increased clogging events has been proven to be wrong. In addition, it is believed that high pressure will cause undesirable shearing of individual particles, thereby causing these particles to tear and break. Surprisingly, after high local shear exposure, small and flexible individual particles remain intact. In addition, the agglomerate groups are able to remain separated during extrusion, rather than simply blocking the small pores of the filter / screen.

[0147] The claimed technology not only enables the sizing of individual particles of viscous injectable materials (such as dermal fillers), but also provides a viable solution for removing agglomerates while retaining the morphological characteristics and features of the individual particles. As discussed previously, formulations with non-uniform particle size or altered morphology may trigger different immune responses, which is undesirable. Most importantly, the pressure-screened material shows zero clogging events, meaning that after the initial characteristic burst / fracture force, there is no pressure buildup in the needle that would cause an expected or controlled immune response. This also avoids the need to employ larger needles or cannulas to deliver viscous formulations, which is not only inconvenient, but may also cause unexpected aggregate delivery, which may again trigger an uneven immune response.

[0148] In an embodiment of the present invention, a method for removing agglomerates of individual particles from a viscous material comprises the steps of: a) filling a viscous material in an extrusion system comprising at least one filter / screen; b) passing the viscous material through a filter / screen placed inside, outside, adjacent to, inline with, or screwed onto the extrusion system, which results in the removal of agglomerates of individual particles from the dermal filler material. In some embodiments, the viscous material is filtered by passing the filler material through an external filter / screen or pressing the extrusion system against the filter / screen, whereby passing the material through the screen results in the removal of agglomerates of individual particles from the viscous material. In some embodiments, the passing step size-adjusts the individual particles of the viscous material to produce a substantially uniform or controlled deposition of the particle matrix. This results in a reduction in the particle size of the viscous material without causing any significant damage to the overall morphology of the individual particles. More importantly, the individual particles retain their characteristic features and rheological properties and have an undamaged morphology.

[0149] In some embodiments, the filter / screen can be a nylon mesh, a stainless steel mesh, a polytetrafluoroethylene (Teflon) mesh, or a nitrocellulose mesh. The selection of the filter material depends on the type of viscous material being filtered. For example, compared with a nylon mesh, a stainless steel mesh can withstand higher pressures and can therefore be used to filter highly viscous materials, while a nylon mesh can be used for less viscous materials. In some embodiments, the viscous material is passed through a screen having a pore size or aperture size that is smaller than the particle size of the viscous material. The filter material and size adjustment may vary according to the type of viscous material, the composition and particle size of the material, and the desired viscosity of the final injectable product. The pore size of the filter / screen is in the range of 1 μm to 1000 μm. In some embodiments, the single particle size is in the range of 20 μm to 1000 μm. In a preferred embodiment, the pore size of the filter / screen is in the range of 25 μm to 500 μm. In this embodiment, the single particle size can be in the range of 40 μm to 500 μm. In another preferred embodiment, the pore size of the filter / screen is in the range of 50 μm to 200 μm. In this embodiment, the single particle size is in the range of 75 μm to 200 μm. In an alternative embodiment, the filter / screen is replaced by an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer, a filter placed inside a filtering device or an extrusion system, a filter screwed onto an extrusion system or a screening channel. The screening channel is a tubular structure, or a cross-shaped mixing device, or a screen with a braided mesh, or a plate with perforations or a net with a connection (nonwoven) hole, to be easier to clean.

[0150] In an embodiment of the invention, immediately after filtering, the filtered viscous material is collected in a loading container / transfer syringe or a second injection device. In some embodiments, the loading container / transfer syringe is a collection chamber in which several batches of filtered material are collected. This is more suitable for large-scale applications or situations involving large amounts of material.

[0151] In an alternative embodiment, the loading container / transfer syringe or the second injection device is an injection-type syringe suitable for direct administration to a patient. An injection-type syringe can also be used as a collection chamber in which filtered material is stored and subsequently transferred to a smaller syringe for administration to a patient. The size of the loading container / transfer syringe may vary depending on whether it is used as a collection device or for direct administration.

[0152] The filtered viscous material is suitable for administration to patients because the filtered viscous material will not clog the loading container / transfer syringe when it is injected from the loading container / transfer syringe. It is noteworthy that due to the removal or breaking of agglomerates, the filtered viscous material has a substantially uniform or controlled extrusion profile, so the filtered material is injected from the loading container / transfer syringe without any pressure accumulation. As previously mentioned, the method breaks up or disassembles agglomerates by efficiently separating individual particles without affecting the rheological properties of these particles. Even after the extrusion process, most of the individual particles of the viscous material are intact or unbroken, that is, they have a substantially uniform, undamaged or minimally damaged morphology after passing through the screen. More specifically, the individual particles undergo the extrusion process without disassembling or damaging the particles, that is, without any effect on the characteristic characteristics and / or morphology of the particles. This is very important for triggering the expected immune response of the patient when the material is administered.

[0153] The extrusion system can be an injection type syringe, a discharge system, a Luer lock connector device or a compressible tube. If an injection type syringe is preferably used, the syringe can have a needle size in the range of 18G to 34G. Similarly, the loading container / transfer syringe can be an injection type syringe, a discharge system, a Luer lock connector device or a compressible tube. If an injection type syringe is preferably used, the syringe of the loading container / transfer syringe can have a needle size in the range of 18G to 34G. In some embodiments, the volume of the extrusion system is similar to the volume of the loading container / transfer syringe. In an alternative embodiment, the volume of the extrusion system is greater than the volume of the loading container / transfer syringe, or wherein, compared with the loading container / transfer syringe, the extrusion system has a lower cross section. In some embodiments, a smaller syringe can also be injected into a larger syringe, and in order to fill a larger syringe, a plurality of smaller syringes can be used or a small syringe can be filled again. Cross-sectional area is usually a consideration for determining the force required for material to pass through the filter / screen.

[0154] In some embodiments, the step of passing is performed using a Luer lock connector injection device, which is provided with at least one filter / screen. In this case, the step of passing is additionally included in forcing the viscous material to pass through the screen under pressure or by applying pressure from an external source. A plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, a roller or a compressor for a flexible tube can be used, or some similar mechanisms are used to apply pressure. In order to prevent individual particles from being accidentally alkalized or causing unnecessary damage to the particle morphology, it is very important to regulate the pressure.

[0155] In an alternative embodiment, the passing step is repeated using a series of filters or screens of different sizes to adjust or reduce the viscosity of the viscous material or adjust the particle size distribution of the viscous material to a desired level, preferably in the range of 50 μm to 750 μm. In some embodiments, the method reduces the extrusion force required to inject the viscous material from the extrusion system. This adjustment of the viscosity and particle size distribution prepares the viscous material (e.g., dermal filler) before it is administered to a patient. In this embodiment, more than one screen / filter can be assembled in the extrusion system so that the viscous material passes through multiple filters of different sizes before the material is filtered out. This can prove useful in embodiments where the viscosity of the material needs to be adjusted before it is administered.

[0156] In an embodiment of the invention, agglomerates present in the viscous material are removed by breaking up the agglomerates or disassembling the agglomerates by separating the individual particles without any impact on their characteristic features or morphology. In an alternative embodiment, the agglomerates are removed by filtering out agglomerates that cannot pass through a filter or screen.

[0157] In some embodiments, before passing through the step, viscous material is pre-filtered by a series of pre-filtering devices. The pre-filtering step can be performed using a series of injection devices, injection-type syringes, discharge systems, injection devices with Luer lock connectors, compressible or incompressible tubes, cylinders or large syringes. In a preferred embodiment, the pre-filtering device is a syringe with different pore sizes, wherein the pore size can be in the range of 18G to 34G. Pre-filtering devices can be selected so that the pre-filtering device has exactly the same size or has a reduced pore size, depending on the amount of agglomerates present in the result of material, experimental design, expectation / requirement and the material. In the case of preferably reducing size, the pore size of the first pre-filtering device is greater than the second pre-filtering device. Accordingly, the pore size of the first pre-filtering device and the second pre-filtering device can be selected from 18G to 34G.

[0158] In some embodiments, the viscous material is pre-filtered prior to the passing step (ie, prior to forcing the material through the screen) through a first pre-filter device and then through a second pre-filter device.

[0159] Dermal fillers are materials commonly used in cosmetic and / or beauty applications, such as filling wrinkles, changing appearance, or addressing soft tissue damage caused by disease or injury. In certain embodiments, dermal filler products can be considered "permanent" because they provide a long-term, natural and biocompatible solution for such applications. Many dermal fillers in this field are temporary. After a period of time, traditional dermal fillers are reabsorbed by the body. Others can use synthetic particles (such as PMMA) to provide a long-term solution. In certain embodiments, dermal fillers are cellulose-based materials that are processed into a target size range for dermal fillers. These can be produced from natural plant polymers and can be permanent because humans do not have enzymes for breaking down cellulose. Therefore, the individual particles of the dermal filler must be within the desired target size range. The individual particles must have a desired SA:V ratio and a desired particle size and viscosity to efficiently promote vascularization, thereby contributing to biocompatibility, so that fillers can be used to provide tissue composed of more of the patient's own tissue rather than synthetic materials.

[0160] In an embodiment of the present invention, a method of removing agglomerates of individual particles from a dermal filler material for administration to a patient is described, the method comprising the steps of: a) filling the dermal filler material in an extrusion system comprising at least one filter / screen; b) passing the dermal filler material through a filter / screen placed inside, outside, adjacent to, inline with, or screwed onto the extrusion system, which removes agglomerates of individual particles from the dermal filler material. In some embodiments, the viscous material is filtered by passing the filler material through an external filter / screen or pressing the extrusion system against the filter / screen. The filtered dermal filler material is suitable for administration to a patient.

[0161] In some embodiments, the passing step sizes individual particles of the viscous dermal filler material to produce a substantially uniform or controlled particle matrix deposition. This allows the particle size of the viscous dermal filler material to be reduced without causing any significant damage to the overall morphology of the individual particles.

[0162] In some embodiments, the filter / mesh can be a nylon mesh, a stainless steel mesh, a polytetrafluoroethylene (Teflon) mesh, or a nitrocellulose mesh. In some embodiments, the viscous dermal filler material is passed through a mesh having a pore size or aperture size that is smaller than the particle size of the viscous dermal filler material. In another embodiment, the pore size of the filter / mesh is in the range of 1 μm to 1000 μm. In this embodiment, the single particle size is in the range of 20 μm to 1000 μm. In a preferred embodiment, the pore size of the filter / mesh is in the range of 25 μm to 500 μm. In this embodiment, the single particle size is in the range of 40 μm to 500 μm. In another preferred embodiment, the pore size of the filter / mesh is in the range of 50 μm to 200 μm. In this embodiment, the single particle size is in the range of 75 μm to 200 μm. The screening channels are tubular structures, or cross-shaped mixing devices, or screens with woven meshes, or plates with perforations or meshes with linked (non-woven) holes for easier cleaning.

[0163] In an embodiment of the invention, immediately after filtering, the filtered viscous dermal filler material is collected in a loading container / transfer syringe. In some embodiments, the loading container / transfer syringe is a collection chamber in which several batches of filtered filler material are collected. This is more suitable for large-scale applications or situations involving large amounts of filler material.

[0164] In an alternative embodiment, the loading container / transfer syringe is an injection-type syringe or a collection syringe suitable for direct administration to a patient. An injection-type syringe can also be used as a collection chamber in which filtered filler material is stored and subsequently transferred to a smaller syringe for administration to a patient. The size of the loading container / transfer syringe may vary depending on whether it is used as a collection device or for direct administration.

[0165] The filtered viscous dermal filler material is suitable for administration to a patient because the filtered viscous dermal filler material does not clog the loading container / transfer syringe when injected from the loading container / transfer syringe. Notably, the filtered viscous dermal filler material has a substantially uniform or controlled extrusion profile due to the removal or breakup of agglomerates caused by the separation of individual particles, so that the filtered viscous dermal filler material is injected from the loading container / transfer syringe without any pressure buildup. Agglomerates are broken down by separating individual particles without affecting the morphological properties of these particles. Even after the extrusion process, a large portion of the individual particles of the viscous filler material are intact or unbroken, i.e., the particles have a uniform, undamaged or minimally damaged morphology after passing through the screen. In some embodiments, at least 98%, at least 95%, at least 92%, at least 89%, at least 86%, at least 83%, or at least 80% of the individual particles of the viscous material pass through the filter / sieve without affecting the characteristic characteristics or morphology of these particles, i.e., the method does not change the characteristic characteristics or morphology of at least 98%, at least 95%, at least 92%, at least 89%, at least 86%, at least 83%, or at least 80% of the individual particles of the viscous material. This is very important for triggering the desired immune response in the patient when the filler material is administered.

[0166] The extrusion system can be an injection type syringe, a discharge system, a Luer lock connector device or a compressible tube. If an injection type syringe is preferably used, the syringe can have a needle size in the range of 18G to 34G. Similarly, the loading container / transfer syringe can be an injection type syringe, a discharge system, a Luer lock connector device or a compressible tube. If an injection type syringe is preferably used, the syringe of the loading container / transfer syringe can have a needle size in the range of 18G to 34G. In some embodiments, the volume of the extrusion system is similar to the volume of the loading container / transfer syringe. In an alternative embodiment, the volume of the extrusion system is greater than the volume of the loading container / transfer syringe, or wherein, compared with the loading container / transfer syringe, the extrusion system has a lower cross section. In some embodiments, a smaller syringe can also be injected into a larger syringe, and in order to fill a larger syringe, a plurality of smaller syringes can be used or a small syringe can be filled again. Cross-sectional area is usually a consideration for determining the force required for material to pass through the filter / screen.

[0167] In some embodiments, the passing step is performed using a Luer lock connector injection device having at least one filter / screen disposed therein. In this case, the passing step further comprises forcing the viscous dermal filler material through the screen under pressure or by applying pressure from an external source. The pressure may be applied using a plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, a roller for a flexible tube, or a compressor, or using some similar mechanism. It is important to regulate the pressure in order to prevent accidental breakage of individual particles or unnecessary damage to the particle morphology.

[0168] In an alternative embodiment, the passing step is repeated using a series of filters or screens of different sizes to adjust or reduce the viscosity or particle size distribution of the viscous dermal filler material to a desired level, preferably in the range of 50 μm to 750 μm. In such an embodiment, more than one screen / filter may be fitted within the extrusion system such that the viscous dermal filler material passes through multiple filters of different sizes before the filler material is filtered out. This may prove useful in embodiments in which the viscosity of the filler material needs to be adjusted prior to its administration. Such adjustments of viscosity and particle size distribution prepare the viscous material (e.g., dermal filler) prior to administration to a patient.

[0169] In an embodiment of the invention, agglomerates present in a viscous dermal filler material are removed by breaking up the agglomerates or breaking up the agglomerates to separate the individual particles. In an alternative embodiment, agglomerates are removed by filtering out agglomerates that cannot pass through a filter or screen.

[0170] In some embodiments, the viscous dermal filler material is pre-filtered through a series of pre-filtering devices, wherein the pre-filtering step occurs before the passing step. The pre-filtering step can be performed using a series of injection devices, injection-type syringes, discharge systems, injection devices with Luer lock connectors, compressible or incompressible tubes, cylinders, or large syringes. In a preferred embodiment, the pre-filtering devices are syringes of different needle sizes, wherein the pre-filtering devices can be selected so that the pre-filtering devices have exactly the same size or have a reduced needle size, depending on the filler material, experimental design, expected / required results, and the amount of agglomerates present in the filler material. In the case of a preferred reduced size, the pore size of the first pre-filtering device is larger than that of the second pre-filtering device. Accordingly, the pore size of the first or second pre-filtering device can be selected from 18G to 34G.

[0171] In some embodiments, the viscous dermal filler material is pre-filtered through a first pre-filter device and then through a second pre-filter device prior to the passing step, ie, prior to forcing the filler material through the screen.

[0172] In an embodiment of the present invention, a method for removing agglomerates of individual particles from a viscous material may include the following steps: a) filling the viscous material in a first collection container including at least one filter / screen; b) passing the viscous material through the filter / screen so that agglomerates of individual particles are removed from the viscous material; and c) collecting the viscous material in a second collection container. In some embodiments, the first collection container may include an extrusion system as described above, and the extrusion system includes a filter / screen. The filtered viscous material collected in the second collection container is suitable for administration to a patient. The collection container may have a mixing capacity in the range of 0.02 gallons to 750 gallons.

[0173] Without being bound by theory, the following chart provides some examples of mixers and vessels currently provided by Charles Ross & Son Company that can be used for large-scale filtration operations. Those skilled in the art will readily appreciate that there may be other vessels that can be used for filtration operations.

[0174]

[0175]

[0176]

[0177] Example of a double planetary mixer provided by Charles Ross & Sons

[0178] In some embodiments, the first collection container is a series of containers with different sizes, a storage unit or chamber, an industrial mixer, an industrial dispenser, an intermediate transfer container, an injection-type syringe, a large injection-type syringe, a Luer lock connector device, a discharge system, or a compressible tube. The second collection device can be selected from at least one of the following: a transfer container, a storage bottle, an injection-type syringe, a filler cartridge, a series of containers with different sizes, a storage unit or chamber, an industrial mixer, an industrial dispenser, an intermediate transfer container, a large injection-type syringe, a Luer lock connector device, a discharge system, or a compressible tube.

[0179] The method of removing agglomerates using a collection container does not change the characteristic characteristics or morphology of at least 98%, at least 95%, at least 92%, at least 89%, at least 86%, at least 83% or at least 80% of the individual particles of the viscous material, that is, at least 98%, at least 95%, at least 92%, at least 89%, at least 86%, at least 83% or at least 80% of the individual particles of the viscous material pass through the filter / sieve without affecting the characteristic characteristics or morphology of these particles.

[0180] In some embodiments, the viscous material is forced through the filter / screen under / by applying pressure using a plunger, extruder, hand compressor, syringe pump, platen compressor, roller or compressor, or using a similar mechanism.

[0181] Without being bound by theory, it is believed that agglomerates are removed from the viscous material by breaking up / disassembling the agglomerates or by filtering out / screening out agglomerates that cannot pass through the filter / screen. The method enables the separation of individual particles without affecting their rheological properties, allowing the agglomerates to be disassembled. The passing step sizes the individual particles of the viscous material to produce a substantially uniform or controlled particle matrix suitable for administration to a patient in need thereof.

[0182] In some embodiments, the viscous material is pre-filtered by a plurality of pre-filtering devices, wherein the pre-filtering step occurs before the passing step. In an alternative embodiment, the viscous material is pre-filtered by a first pre-filtering device followed by a second pre-filtering device, wherein the plurality of pre-filtering devices are syringes with different pore sizes. The pre-filtering step can be performed using a series of injection devices, injection-type syringes, discharge systems, injection devices with Luer lock connectors, compressible or incompressible tubes, cylinders, or large syringes. In some embodiments, the pore size of the first pre-filtering device is larger than that of the second pre-filtering device. The pore size of the first and second pre-filtering devices can be selected from 18G to 34G.

[0183] In some embodiments, the viscous material is passed through at least one filter / screen having a pore size / aperture size that is smaller than the particle size of the viscous material, wherein the pore size of the filter / screen is in the range of 1 μm to 1000 μm. In such embodiments, the individual particle size may be in the range of 20 μm to 1000 μm. In some embodiments, the pore size of the filter / screen is in the range of 25 μm to 500 μm or in the range of 50 μm to 200 μm. In such embodiments, the individual particle size may be in the range of 40 μm to 500 μm or 75 μm to 200 μm.

[0184] The filtered viscous material that can be collected in a second collection container is dispensed / injected using a dispensing device, wherein the filtered viscous material does not clog the dispensing device when being dispensed / injected from the dispensing device. The filtered viscous material has a substantially uniform or controlled extrusion profile when being dispensed / injected from the dispensing device, wherein the filtered viscous material is dispensed / injected from the dispensing device without any pressure buildup after an initial characteristic burst / fracture force.

[0185] In some embodiments, the dispensing device is an industrial filtration unit, a large injection device, a screw driven extruder, a hydraulic platen pump or a discharge system. In a preferred embodiment, the dispensing device is a syringe, wherein the syringe has a needle size of 18G to 34G. In some embodiments, the filter / screen is a nylon mesh, a stainless steel mesh, a polytetrafluoroethylene mesh or a nitrocellulose mesh. In an alternative embodiment, the filter / screen is replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer, a filter placed inside a filter, a filter screwed onto a filter or a sieving channel.

[0186] In some embodiments, the filter / screen is disposed within the Luer lock connector / Luer lock connector portion of the first collection container assembled within the first collection container, wherein the viscous material is forced under pressure / by applying pressure through the filter / screen disposed within the Luer lock connector portion. In such embodiments, wherein the pressure is applied using a plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, a roller for a flexible tube, or a compressor, or using some similar mechanism.

[0187] In some embodiments, the passing step can be repeated using multiple filters / screens to adjust or reduce the viscosity or particle size distribution of the viscous material to a desired level, preferably in the range of 50 μm to 750 μm, wherein the multiple filters / screens have the same size or have different sizes in the range of 1 μm to 1000 μm. This adjustment of viscosity and particle size distribution prepares the viscous material (e.g., dermal filler) before administering it to a patient. The method reduces the extrusion force required to inject the viscous material from the extrusion system.

[0188] In some embodiments, the second collection container is used to dispense / inject the filtered viscous material for administration to a patient, wherein the volume of the first collection container is larger than the second collection container.

[0189] In some embodiments, the methods described above can be used to adjust the viscosity of a viscous material or a dermal filler material to a desired level. In some embodiments, the methods described above can be used to break down agglomerates / aggregates in a viscous material or a dermal filler material. The methods described may also prove useful when preventing needle clogging in an injection device is of great significance, especially during the delivery of a viscous material or any dermal filler material. In addition, the methods described can help to size individual particles of a viscous material so that the viscous material or the dermal filler material has an almost uniform particle size. In addition, the method can be used to reduce the particle size of a viscous material or a dermal filler material without affecting / impacting the rheological properties of these materials, so that the viscous material or the dermal filler material has a substantially uniform or controlled particle matrix deposition. In some embodiments, the method reduces the extrusion force required to inject a viscous material from an extrusion system.

[0190] The described method can be used for a wide range of viscous materials. Without limiting the scope of its application, the method can be used to process the following viscous materials such as dermal fillers; sealants; adhesives; composite mixtures of mammalian cells; scaffold materials; bone paste; bone cement; cartilage biomaterials; injectables including venous stasis applications; protein hydrogels; carbohydrate hydrogels including cellulose, pectin and lignin; cellular material mixtures; thickeners; gelling agents; and stabilizers. The described method can also be used to remove agglomerates from other materials such as glues and hydrocolloids, cassia gum powder, guar gum powder, instant guar gum powder, cassia powder, tamarind kernel powder, sesbania gum powder, fenugreek gum powder, psyllium husk powder, kappa carrageenan powder, locust bean gum powder, date palm mucus, guar bean powder, "Erva Baleeira" mucilage, guar gum, kondagogu gum, konjac glucomannan, taro, gellan gum, curdlan gum, starch, wheat starch, corn starch, barley starch, modified starch, kudzu starch, corn starch, tapioca flour, potato starch, stabilizer, gum arabic (gum arabic), agar, ammonium alginate, calcium alginate, carob gum (locust bean gum), carrageenan extract (carrageenan), ghatti gum, guar gum, pectin, potassium alginate, sodium alginate, karaya gum (karaya gum), tragacanth gum (tragacanth gum ), thickeners, sodium alginate, potassium alginate, alginate amine, calcium alginate, carrageenan, locust bean gum, guar gum, karaya gum, gellan gum, mannitol, konjac, pectin, cellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, isomalt, maltitol, xylitol, oxidized starch, monostarch phosphate, distarch phosphate, gelling agents, alginic acid, sodium alginate, potassium alginate, agar, carrageenan, locust bean gum, gellan gum, konjac, pectin, cellulose, methylcellulose, hydroxypropyl cellulose and hydroxypropyl methylcellulose.

[0191] In some embodiments, the method can be used to reduce the particle size of the material, thereby reducing the extrusion force required to inject a viscous material from an extrusion system. In some embodiments, the method can help reduce the viscosity of a viscous material or dermal filler material to a range of 1% to 99%. In some embodiments, the method can be used to filter and extrude a viscous material using a controlled or uniform extrusion force.

[0192] In some embodiments, a device for removing agglomerates of individual particles from a viscous material is described, the device comprising the following elements: a) an extrusion system; b) at least one filter / screen placed inside, outside, adjacent to, inline with, or screwed onto the extrusion system, which enables the removal of agglomerates of individual particles from the dermal filler material. In some embodiments, the viscous material is filtered by passing the filler material through an external filter / screen or pressing the extrusion system against the filter / screen, which enables the removal of agglomerates of the viscous / dermal filler material as the material passes through the filter / screen.

[0193] In some embodiments, the device may further comprise an extruder for forcing the viscous / dermal filler material through the filter / screen under pressure. The extruder pressure may be regulated by electronic or mechanical means.

[0194] The filter / screen can be selected from a nylon screen, a stainless steel screen, a polytetrafluoroethylene (Teflon) screen, or a nitrocellulose screen. In some embodiments, the filter / screen is a nylon screen. The nylon screen used in the process can be replaced with a more robust solution suitable for large-scale operations. For example, an inline 316 stainless steel screen (with several different size options) can be used instead of a nylon screen.

[0195] The filter / screen can have a pore size in the range of 1 μm to 1000 μm. In this embodiment, the single particle size can be in the range of 20 μm to 1000 μm. In a preferred embodiment, the pore size of the filter / screen is in the range of 25 μm to 500 μm. In this embodiment, the single particle size can be in the range of 40 μm to 500 μm. In another preferred embodiment, the pore size of the filter / screen is in the range of 50 μm to 200 μm. In this embodiment, the single particle size can be in the range of 75 μm to 200 μm. In an alternative embodiment, the filter / screen is replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer, a filter placed inside a filter device, a filter screwed onto a filter device or a sieving channel. The size of the inline filter can be in the range of 0.5 mm to 2540 mm. The screening channels are tubular structures, or cross-shaped mixing devices, or screens with woven meshes, or plates with perforations or meshes with linked (non-woven) holes for easier cleaning.

[0196] In an alternative embodiment, the design of the device can be modified so that the extrusion system is connected to a series of pre-filtering devices so that the viscous material or dermal filler material is at least pre-filtered before passing through the filter / screen. In such an embodiment, the extrusion system is connected to at least one pre-filtering device, and the pre-filtering device is linked to a loading container / transfer syringe. The loading container / transfer syringe can simply be a collection chamber for collecting and storing filtered material, especially in cases where multiple batches of material are filtered / pre-filtered. In some other embodiments, the loading container / transfer syringe can be used to administer the material to the patient.

[0197] The extrusion system can be an injection-type syringe, a discharge system, a Luer lock connector device or a compressible tube. The loading container / transfer syringe can be an injection-type syringe, a discharge system, a Luer lock connector device or a compressible tube. At least one pre-filter device can be a series of injection devices, syringes, a discharge system, an injection device with a Luer lock connector, a compressible or incompressible tube, a cylinder or a large syringe. The injection device can have a needle size in the range of 18G to 34G. In some embodiments, the volume of the extrusion system can be greater than the volume of the loading container / transfer syringe, or wherein the extrusion system has a lower cross-section compared to the loading container / transfer syringe. For example, the extrusion system and the loading container / transfer syringe can be 1ml syringes, or in an alternative embodiment, the extrusion system can be a 5ml syringe and the transfer syringe can be a 1ml syringe. In this case, the aperture size of the extrusion system can be greater than the aperture size of the loading container / transfer syringe. In some embodiments, a smaller syringe can also be injected into a larger syringe, and in order to fill a larger syringe, multiple smaller syringes can be used or a small syringe can be filled again. Cross-sectional area is usually a consideration for determining the force required for the material to pass through the filter / screen.

[0198] In some embodiments, the filter / sieve used in the final pass / filtration step has a pore size smaller than the particle size of the viscous material. The smaller size facilitates the alkalinization of the particles to achieve a substantially uniform or controlled particle distribution. The pore size of the filter / sieve may be in the range of 1 μm to 1000 μm.

[0199] In some embodiments, the Luer lock connector can be assembled within the extrusion system. The Luer lock connector can accommodate the filter / screen, ie, the filter / screen can be placed in the Luer lock connector instead of placing the filter / screen at the bottom of the first injection device.

[0200] In an alternative embodiment, the device may have a slightly different configuration, wherein the device for removing agglomerates may include: a) a first collecting device; b) at least one filter / sieve mounted inside the first collecting device, through which the viscous / dermal filler material passes so that agglomerates of individual particles are removed from the material; and c) a second collecting device coupled to the first collecting device for collecting the filtered material.

[0201] In such an embodiment, the first collection device can be a series of containers with different sizes, a storage unit or chamber, an industrial mixer, an industrial dispenser, an intermediate transfer container, a Luer lock connector device, an injection-type syringe, a large injection-type syringe, a discharge system, or a compressible tube. In an alternative embodiment, the second collection device can be a transfer container, a storage bottle, an injection-type syringe, a filler cartridge, a series of containers with different sizes, a storage unit or chamber, an industrial mixer, an industrial dispenser, an intermediate transfer container, a large injection-type syringe, a Luer lock connector device, a discharge system, or a compressible tube.

[0202] In some embodiments, an additional filter / sieve is assembled in the second collection device. In this embodiment, the pore size of the first filter / sieve and the pore size of the additional filter / sieve can be in the range of 1 micron to 1000 microns. In this embodiment, the single particle size can be in the range of 20μm to 1000μm. In a preferred embodiment, the pore size of the filter / sieve is in the range of 25μm to 500μm. In this embodiment, the single particle size can be in the range of 40μm to 500μm. In another preferred embodiment, the pore size of the filter / sieve is in the range of 50μm to 200μm. In this embodiment, the single particle size can be in the range of 75μm to 200μm. The filter / sieve can be nylon, stainless steel, Teflon or nitrocellulose. In some preferred embodiments, the filter / sieve can be a nylon mesh or a stainless steel mesh. In alternative embodiments, the filter / screen is replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer, a filter placed inside a filter device, a filter screwed onto a filter device or a screening channel. The size of the inline filter can range from 0.5 mm to 2540 mm. The screening channel is a tubular structure, or a cross-shaped mixing device, or a screen with a woven mesh, or a plate with perforations or a mesh with coupling (non-woven) holes for easier cleaning.

[0203] In some configurations, the second collecting device is a collecting chamber disposed within the first collecting device. In such an embodiment, the viscous material is stored in the chamber (ie, the second collecting device mounted within the first collecting device) after passing through the filter / screen mounted within the first collecting device.

[0204] In some embodiments, the device may further include an extruder for forcing the viscous / dermal filler material through a filter / screen under pressure. The extruder pressure can be adjusted by electronic or mechanical means. Alternatively, a plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, a roller for a flexible tube, or a compressor, or some similar mechanism can be used to apply pressure. In order to prevent the particles from being accidentally alkalized or causing unnecessary damage to the particle morphology, it is very important to adjust the pressure. The extruder pressure can be adjusted by electronic or mechanical means.

[0205] In an alternative embodiment, the design of the device can be modified so that the first collection device is connected to a series of pre-filter collection devices, so that the viscous material or dermal filler material is at least pre-filtered before passing through the filter / screen. In such an embodiment, the first collection device is connected to at least one pre-filter collection device, and the pre-filter device is linked to the second collection device. The second collection device can simply be a collection chamber for collecting and storing filtered material, especially in cases where multiple batches of material are filtered / pre-filtered. The collected material can be transferred to a dispensing / dosing / injection device or syringe for ultimate administration of the filtered material to a patient.

[0206] The first collecting device can be a series of containers with different sizes, storage units or chambers, Luer lock connector devices, industrial mixers, industrial distributors, intermediate transfer containers, injection type syringes, large injection type syringes, discharge systems or compressible tubes. The second collecting device can be a transfer container, a storage bottle, an injection type syringe, a filler barrel, a series of containers with different sizes, storage units or chambers, industrial mixers, industrial distributors, intermediate transfer containers, large injection type syringes, Luer lock connector devices, discharge systems or compressible tubes. At least one pre-filtering device can be a series of injection devices, syringes, discharge systems, injection devices with Luer lock connectors, compressible or incompressible tubes, cylinders or large syringes. Distribution / dosing / injection device can be a series of injection devices, injection type syringes, Luer lock syringes, large syringes, and can have a needle size in the range of 18G to 34G.

[0207] Similar to other device configurations, in some embodiments, the filter / screen used for the final pass / filtration step has a pore size that is smaller than the particle size of the viscous material. The smaller size facilitates the alkalinization of the particles to achieve a substantially uniform or controlled particle distribution. The pore size of the filter / screen can range from 1 micron to 1000 microns.

[0208] In some embodiments, the Luer lock connector can fit inside the first collecting device. The Luer lock connector can accommodate the filter / screen, i.e., the filter / screen can be placed inside the Luer lock connector instead of placing the filter / screen at the bottom of the first collecting device.

[0209] Potential solutions and configurations

[0210] The invention will now be described in terms of an exemplary potential configuration that can be used to implement a pressure sieving process to remove agglomerates of individual particles from a given viscous material. There are a variety of potential applications for the claimed technology, such as filtering agglomerates from pharmaceutical formulations, dermal filler applications, soft tissue implants, lubricants, and carriers for small peptide or cell delivery.

[0211] Figure 8 An inline pressure filtration process that can be used for a large-scale implementation of a pressure filtration / screening process is shown. The inline pressure filtration system includes a discharge system for forcing viscous material through a mesh screen. In an implementation of the inline process, the mesh screen can be assembled between the discharge system (injection device) and a collection container (such as a loading container). The schematic diagram of the inline mesh screen shown in the figure was provided by Charles Ross and Sons (left portion of the figure). The filtered viscous material is collected in the collection container before being transferred to a smaller transfer syringe.

[0212] As shown, the screen can be a mesh screen that can be pre-assembled in the discharge system or can be assembled before the filtering process. The syringe can be placed between the syringe adapter and the discharge system in front of the fill tube extension. As mentioned earlier, this configuration is more suitable for use with high viscosity materials or in situations where several batches of material are processed simultaneously.

[0213] Generally speaking, the discharge system includes a large container, a platen or extruder, a valve and an extrusion port, and when the valve is opened, the platen pushes the material out of the extrusion port.

[0214] Fig. 9Shown is a syringe process configuration for handling viscous materials and removing agglomerates. In the syringe process, an injection device pre-assembled with a filter / screen is used. The small filter used in the inline pressure filtration process is placed toward the bottom of the internal injection device so that the viscous material passes through the filter / screen before leaving the injection device. The filtered material can be collected in a loading container / transfer syringe or a separate collection container. In this configuration, the filtering force is provided by an extruder. The extruder force forces the material to pass through the filter / screen so that the material passes through the filter and is filtered before leaving the injection device. In some embodiments, the filtered material can be administered to the patient by collecting the filtered material in a small transfer syringe. In this case, there is no collection device to collect the filtered viscous material because the material is administered directly to the patient using a transfer syringe. In an alternative embodiment, the filtered material can be stored in a separate collection container. This configuration (i.e., syringe process) is more suitable for small-scale applications.

[0215] In some embodiments, the injection device is a syringe with a needle size of 18G to 34G. The filter / screen placed at the base of the syringe can be selected from a nylon mesh, a stainless steel mesh, a polytetrafluoroethylene (Teflon) mesh, or a nitrocellulose mesh. The loading container / transfer syringe can be an injection-type syringe, a discharge system, a Luer lock connector device, or a compressible tube. The types of viscous materials that can be filtered using this process are dermal fillers; sealants; adhesives; composite mixtures of mammalian cells; scaffold materials; bone paste; bone cement; cartilage biomaterials; injectables including venous stasis applications; protein hydrogels; carbohydrate hydrogels including cellulose, pectin, and lignin; cell material mixtures; thickeners; gelling agents; and stabilizers. The described method can also be used to remove agglomerates from other materials such as gums and hydrocolloids, cassia gum powder, guar gum powder, instant guar gum powder, cassia seed powder, tamarind kernel powder, sesbania gum powder, fenugreek gum powder, psyllium husk powder, kappa carrageenan powder, locust bean gum powder, date palm mucilage, guar bean powder, "Erva Baleeira" mucilage, guar gum, kondagogu gum, konjac glucomannan, taro, gellan gum, curdlan gum, starch, wheat starch, corn starch, barley starch, modified starch, kudzu starch, corn starch, tapioca flour, potato starch, stabilizers, gum arabic (gum arabic), agar, ammonium alginate, calcium alginate, carob gum (locust bean gum), carrageenan extract (carrageenan), ghatti gum, guar gum, pectin, potassium alginate, sodium alginate, karaya gum, tragacanth gum (tragacanth gum ), thickeners, sodium alginate, potassium alginate, alginate amine, calcium alginate, carrageenan, locust bean gum, guar gum, karaya gum, gellan gum, mannitol, konjac, pectin, cellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, isomalt, maltitol, xylitol, oxidized starch, monostarch phosphate, distarch phosphate, gelling agents, alginic acid, sodium alginate, potassium alginate, agar, carrageenan, locust bean gum, gellan gum, konjac, pectin, cellulose, methylcellulose, hydroxypropyl cellulose and hydroxypropyl methylcellulose.

[0216] Fig.10 An inline syringe process configuration is shown in which a small filter / screen is placed between the needle and syringe in a custom Luer lock connector arrangement. The Luer lock connector syringe is able to provide leak-proof transfer of material between the syringe and the needle, and most importantly, the Luer lock connector syringe provides protection against accidental removal of the needle or accidental leakage of the material contents. In this configuration, the filtering force can also be provided by the extruder, and similar to the inline syringe process, the material is filtered immediately before reaching the needle. In this configuration, the filter is not placed in the syringe. The intermediate Luer lock connection provides for simple and quick attachment of the filter / screen.

[0217] The processed / filtered material presents a significant filling challenge due to its high viscosity. To avoid disrupting the end cap seal of the injection device / syringe and to prevent excessive silicone shedding during multiple plunger passes, a large transfer needle (particularly an 8G to 10G needle) can be utilized to backfill the material. The stopper is then placed using a commercially available vent tube blocking method.

[0218] The overall concept of the present invention is to use pressure driven filtration to break up agglomerates and filter out large individual particles. This concept can be applied at multiple levels or scales. In its simplest form, the process involves passing bulk material through a small opening (such as a mesh screen or perforated plate) and then collecting the filtered material in a small syringe or collection container. The concept of the filtration process is as follows Fig.11 The block diagram is shown in form.

[0219] The techniques of the present invention may be applied multiple times and / or at various scales. Fig.12 Block diagrams showing how the process can be applied on large, medium and small scales are provided.

[0220] Fig.12 (I) shows the example of large-scale operation. In large-scale operation, the incoming material (or material to be processed) is in large quantities. Large quantities of materials can be disposed in industrial high viscosity mixers / distributors, wherein the filter / screen can be an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer, or a filter that is screwed onto or assembled in the mixer / distributor unit. The processed or filtered materials can be collected in large containers or multiple smaller containers. Alternatively, the materials can be stored in storage bottles, large transfer syringes or filling cylinders.

[0221] Fig.12 (II) shows an exemplary medium-scale operation. In a medium-scale operation, the incoming material (or material to be processed) can also be in large quantities. The material can be processed in an intermediate transfer container (such as a filling line, a large syringe, a filling cylinder). Large batches of material can be processed in an intermediate container, wherein the filter can be a mesh screen, a filter head placed in the intermediate container, or a Luer lock attachment fixed to the intermediate container. The processed or filtered material can be collected in a large container or multiple smaller containers. Alternatively, the material can be filled in a final transfer syringe for injection / direct administration to the patient.

[0222] Fig.12(III) shows an exemplary small-scale operation. In a small-scale operation, the material to be filtered / processed is filled in a final transfer syringe for direct injection into a patient, such as a 1cc syringe. A filter / screen (e.g., a mesh filter) can be placed inside the final syringe (or screwed onto the outlet of the final syringe) for injection into a patient. For example, a mesh Luer lock attachment between the syringe and the needle is used to inject into a patient. In this case, the processed / filtered material is administered directly to the patient's body without the need for any storage or collection container.

[0223] Each approach has different applications or advantages. For materials that reassemble and easily reform into aggregates, small-scale processing immediately prior to injection into a patient would be very appropriate. In contrast, for less viscous materials, large- or medium-scale operations would be more appropriate. These operations have higher throughput and involve lower material costs than small-scale approaches.

[0224] As those skilled in the art will appreciate, one or more illustrative embodiments have been described by way of example. Those skilled in the art will appreciate that numerous variations and modifications may be made without departing from the scope of the invention as defined in the claims.

Claims

1. A method for removing agglomerates of individual particles from a viscous material for administration to a patient, comprising: filling the viscous material in an extrusion system comprising at least one filter / screen; Passing the viscous material through the at least one filter / mesh causes agglomerates of the individual particles to be removed from the viscous material; wherein the filtered viscous material is suitable for administration to the patient.

2. The method according to claim 1, wherein: The method does not alter the characteristic features or morphology of at least 98%, at least 95%, at least 92%, at least 89%, at least 86%, at least 83% or at least 80% of the individual particles of the viscous material.

3. The method according to claim 1, wherein: The passing step further comprises forcing the viscous material through the at least one filter / screen under / by applying pressure.

4. The method according to claim 3, wherein: The viscous material is forced through the at least one filter / screen by applying pressure using a plunger, extruder, hand compressor, syringe pump, platen compressor, rollers for flexible tubing, compressor, or a device capable of employing a similar mechanism.

5. The method according to claim 1, wherein: The agglomerates are removed from the viscous material by breaking up / disassembling the agglomerates.

6. The method according to claim 1, wherein: The agglomerates are removed from the viscous material by filtering / sieving out the agglomerates that cannot pass through the at least one filter / screen.

7. The method according to claim 1, wherein: The viscous material is pre-filtered through a plurality of pre-filtering devices, wherein the pre-filtering step occurs before the passing step.

8. The method according to claim 7, wherein: The viscous material is pre-filtered through a first pre-filter device and then through a second pre-filter device.

9. The method according to claim 7, wherein: The plurality of pre-filtration devices are a series of injection devices, injection-type syringes, a discharge system, an injection device with a Luer lock connector, a compressible tube, a non-compressible tube, a cylinder or a large syringe.

10. The method according to claim 8, wherein: The first pre-filtering device and the second pre-filtering device are a series of injection devices, injection-type syringes or large syringes, wherein the pore size of the first pre-filtering device is larger than the pore size of the second pre-filtering device.

11. The method according to claim 8, wherein: The pore size of the first pre-filtering device is in the range of 18G to 34G.

12. The method according to claim 8, wherein: The pore size of the second pre-filtering device is in the range of 18G to 34G.

13. The method according to claim 1, wherein: The viscous material is passed through the at least one filter / screen having a pore size / aperture size smaller than the size of individual particles of the viscous material.

14. The method according to claim 13, wherein: The pore size of the at least one filter / mesh is in the range of 1 μm to 1000 μm, and the individual particle size is in the range of 20 μm to 1000 μm.

15. The method according to claim 13, wherein: The pore size of the at least one filter / mesh is in the range of 25 μm to 500 μm, and the individual particle size is in the range of 40 μm to 500 μm.

16. The method according to claim 13, wherein: The pore size of the at least one filter / mesh is in the range of 50 μm to 200 μm, and the individual particle size is in the range of 75 μm to 200 μm.

17. The method according to claim 1, wherein: The filtered viscous material was collected in a loading container / transfer syringe.

18. The method according to claim 17, wherein: The filtered viscous material will not clog the loading container / transfer syringe when injected from the loading container / transfer syringe.

19. The method according to claim 18, wherein: The filtered viscous material has a substantially uniform or controlled extrusion profile when injected from the loading container / transfer syringe.

20. The method according to claim 19, wherein: The filtered viscous material is ejected from the loading container / transfer syringe after the initial characteristic burst / break force without any pressure build-up.

21. The method according to claim 1, wherein: The individual particles of the viscous material have an intact morphology.

22. The method according to claim 1, wherein: The filtered viscous material triggers a desired immune response in the patient following administration.

23. The method according to claim 1, wherein: The extrusion system is selected from the group consisting of an injectable syringe, an expulsion system, a Luer lock connector device, or a compressible tube.

24. The method according to claim 23, wherein: The extrusion system is a syringe, wherein the syringe has a needle size in the range of 18G to 34G.

25. The method of claim 1, wherein: The loading container / transfer syringe is selected from the group consisting of an injection-type syringe, an ejection system, a Luer lock connector device, or a compressible tube.

26. The method according to claim 25, wherein: The loading container / transfer syringe is a syringe, wherein the syringe has a needle size of 18G to 34G.

27. The method according to any one of claims 17 to 26, wherein: The volume of the extrusion system is greater than the volume of the loading container / transfer syringe, or wherein the extrusion system has a lower cross-section than the loading container / transfer syringe.

28. The method according to any one of claims 1 to 27, wherein: The at least one filter / mesh is selected from the group consisting of: a nylon mesh, a stainless steel mesh, a polytetrafluoroethylene mesh, or a nitrocellulose mesh.

29. The method according to any one of claims 1 to 27, wherein: The at least one filter / screen is placed inside, outside, adjacent to or screwed onto the extrusion system.

30. The method of claim 1, wherein: The at least one filter / screen is replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer or a screening channel.

31. The method according to any one of claims 1 to 30, wherein: The passing step sizes the individual particles of the viscous material to produce a substantially uniform or controlled particle matrix for administration.

32. The method of claim 1, wherein: The extrusion system is a Luer lock connector device, wherein the at least one filter / screen is assembled / disposed within the Luer lock connector portion of the device.

33. The method of claim 32, wherein: The viscous material is forced under / by applying pressure through the at least one filter / screen mounted / arranged within the Luer lock connector portion.

34. The method of claim 33, wherein: The pressure is applied using a plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, rollers for flexible tubing, a compressor, or a device capable of employing a similar mechanism.

35. The method of claim 33, wherein: The pressure is applied using a plunger or an extruder.

36. The method of claim 1, wherein: The passing step is repeated using multiple filters / screens.

37. The method of claim 36, wherein: The multiple filters / screens may be of the same size or of different sizes.

38. The method of claim 36, wherein: The at least one filter / mesh has a pore size in the range of 1 μm to 1000 μm.

39. The method according to any one of claims 36 to 38, wherein: Passing the material through a plurality of filters / screens reduces the viscosity of the viscous material or adjusts the particle size distribution of the viscous material to a desired level, preferably in the range of 50 μm to 750 μm.

40. The method of claim 31, wherein: The method reduces the extrusion force required to inject the viscous material from the extrusion system.

41. The method of claim 1, wherein: The viscous material is selected from the group consisting of: dermal fillers; sealants; adhesives; composite mixtures of mammalian cells; scaffold materials; bone paste; bone cement; cartilage biomaterials; Injectables include those for venous stasis applications; protein hydrogels; carbohydrate hydrogels including cellulose, pectin, and lignin; cell material mixtures; thickeners; gelling agents; and stabilizers.

42. A method of removing agglomerates of individual particles from a cohesive dermal filler material for administration to a patient, comprising: filling the dermal filler material in an extrusion system comprising at least one filter / screen; Passing the dermal filler material through the at least one filter / mesh causes agglomerates of the individual particles to be removed from the dermal filler material; wherein the filtered dermal filler material is suitable for administration to the patient.

43. The method of claim 42, wherein: The method does not alter the characteristic features or morphology of at least 98%, at least 95%, at least 92%, at least 89%, at least 86%, at least 83% or at least 80% of the individual particles of the dermal filler material.

44. The method of claim 42, wherein: The passing step further comprises forcing the dermal filler material through the at least one filter / mesh under / by applying pressure.

45. The method of claim 44, wherein: The dermal filler material is forced through the at least one filter / screen by applying pressure using a plunger, extruder, manual compressor, syringe pump, platen compressor, rollers for flexible tubing, compressor, or a device capable of employing a similar mechanism.

46. ​​The method of claim 42, wherein: The agglomerates are removed from the dermal filler material by breaking up / disassembling the agglomerates.

47. The method of claim 42, wherein: The agglomerates are removed from the dermal filler material by filtering out / sieving out the agglomerates that are unable to pass through the at least one filter / sieve.

48. The method of claim 42, wherein: The dermal filler material is pre-filtered through a plurality of pre-filtering devices, wherein the pre-filtering step occurs before the passing step.

49. The method of claim 48, wherein: The viscous material is pre-filtered through a first pre-filter device and then through a second pre-filter device.

50. The method of claim 48, wherein: The plurality of pre-filtration devices are selected from the group consisting of a series of injection devices, an injection-type syringe, a drain system, an injection device with a Luer lock connector, a compressible tube, a non-compressible tube, a cylinder, or a large syringe.

51. The method of claim 49, wherein: The plurality of pre-filtering devices are a series of injection devices, syringe-type syringes or large syringes, wherein the first pre-filtering device has a larger pore size than the second pre-filtering device.

52. The method of claim 51, wherein: The pore size of the first pre-filtering device is in the range of 18G to 34G.

53. The method of claim 51, wherein: The pore size of the second pre-filtering device is in the range of 18G to 34G.

54. The method of claim 42, wherein: The dermal filler material is passed through the at least one filter / mesh having a pore size / pore size smaller than the size of individual particles of the viscous material.

55. The method of claim 42, wherein: The pore size of the at least one filter / mesh is in the range of 1 μm to 1000 μm, and the individual particle size is in the range of 20 μm to 1000 μm.

56. The method of claim 42, wherein: The pore size of the at least one filter / mesh is in the range of 25 μm to 500 μm, and the individual particle size is in the range of 40 μm to 500 μm.

57. The method of claim 42, wherein: The pore size of the at least one filter / mesh is in the range of 50 μm to 200 μm, and the individual particle size is in the range of 75 μm to 200 μm.

58. The method of claim 42, wherein: The filtered dermal filler material is collected in a loading container / transfer syringe.

59. The method of claim 58, wherein: The filtered dermal filler material will not clog the loading container / transfer syringe when injected from the loading container / transfer syringe.

60. The method of claim 59, wherein: The filtered dermal filler material has a substantially uniform or controlled extrusion profile when injected from the loading container / transfer syringe.

61. The method of claim 60, wherein: The filtered dermal filler material is injected from the loading container / transfer syringe without any pressure build-up after the initial characteristic burst / break force.

62. The method of claim 42, wherein: The individual particles of the dermal filler material have an intact morphology.

63. The method of claim 42, wherein: The filtered dermal filler material triggers a desired immune response in the patient following administration.

64. The method of claim 42, wherein: The extrusion system is selected from the group consisting of an injectable syringe, an expulsion system, a Luer lock connector device, or a compressible tube.

65. The method of claim 64, wherein: The extrusion system is a syringe, wherein the syringe has a needle size in the range of 18G to 34G.

66. The method of claim 42, wherein: The loading container / transfer syringe is selected from the group consisting of an injection-type syringe, an ejection system, a Luer lock connector device, or a compressible tube.

67. The method of claim 66, wherein: The loading container / transfer syringe is a syringe, wherein the syringe has a needle size of 18G to 34G.

68. The method according to any one of claims 58 to 67, wherein: The volume of the extrusion system is greater than the volume of the loading container / transfer syringe, or wherein the extrusion system has a lower cross-section than the loading container / transfer syringe.

69. The method according to any one of claims 42 to 68, wherein: The at least one filter / mesh is selected from the group consisting of: a nylon mesh, a stainless steel mesh, a polytetrafluoroethylene mesh, or a nitrocellulose mesh.

70. The method according to any one of claims 42 to 69, wherein: The at least one filter / screen is placed inside, outside, adjacent to or screwed onto the extrusion system.

71. The method of claim 42, wherein: The at least one filter / screen is replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer or a screening channel.

72. The method of any one of claims 42 to 71, wherein: The passing step sizes the individual particles of the dermal filler material to produce a substantially uniform or controlled particle matrix for administration.

73. The method of claim 42, wherein: The extrusion system is a Luer lock connector device, wherein the at least one filter / screen is assembled / disposed within the Luer lock connector portion of the device.

74. The method of claim 73, wherein: The dermal filler material is forced under / by applying pressure through the at least one filter / mesh mounted / disposed within the Luer lock connector portion.

75. The method of claim 74, wherein: The pressure is applied using a plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, rollers for flexible tubing, a compressor, or a device capable of employing a similar mechanism.

76. The method of claim 74, wherein: The pressure is applied using a plunger or an extruder.

77. The method of claim 42, wherein: The passing step is repeated using multiple filters / screens.

78. The method of claim 77, wherein: The multiple filters / screens may be of the same size or of different sizes.

79. The method of claim 79, wherein: The at least one filter / mesh has a pore size in the range of 1 μm to 1000 μm.

80. The method of any one of claims 77 to 79, wherein: Passing the material through a plurality of filters / sieves reduces the viscosity of the dermal filler material or adjusts the particle size distribution of the dermal filler material to a desired level, preferably in the range of 50 μm to 750 μm.

81. The method of claim 80, wherein: The method reduces the extrusion force required to inject the dermal filler material from the extrusion system.

82. The method of claim 35, wherein: The dermal filler material is selected from the group consisting of: a sealant; an adhesive; a composite mixture of mammalian cells; a scaffold material; a bone paste; a bone cement; a cartilage biomaterial; Injectables include those for venous stasis applications; protein hydrogels; carbohydrate hydrogels including cellulose, pectin, and lignin; cell material mixtures; thickeners; gelling agents; and stabilizers.

83. A method of removing agglomerates of individual particles from a viscous material for administration to a patient, comprising: filling the viscous material in a first collection container comprising at least one filter / screen; passing the viscous material through the at least one filter / screen such that agglomerates of the individual particles are removed from the viscous material; The viscous material is collected in a second collection container, wherein the filtered viscous material collected in the second collection container is suitable for administration to the patient.

84. The method of claim 83, wherein: The first collection container comprises an extrusion system, wherein the extrusion system comprises the at least one filter / screen.

85. The method of claim 83, wherein: The method does not alter the characteristic features or morphology of at least 98%, at least 95%, at least 92%, at least 89%, at least 86%, at least 83% or at least 80% of the individual particles of the viscous material.

86. The method of claim 83, wherein: The passing step further comprises forcing the viscous material through the at least one filter / screen under / by applying pressure.

87. The method of claim 70, wherein: The viscous material is forced through the at least one filter / screen by applying pressure using a plunger, extruder, hand compressor, syringe pump, platen compressor, rollers for flexible tubing, compressor, or a device capable of employing a similar mechanism.

88. The method of claim 83, wherein: The agglomerates are removed from the viscous material by breaking up / disassembling the agglomerates.

89. The method of claim 83, wherein: The agglomerates are removed from the viscous material by filtering / sieving out the agglomerates that cannot pass through the at least one filter / screen.

90. The method of claim 83, wherein: The viscous material is pre-filtered through a plurality of pre-filtering devices, wherein the pre-filtering step occurs before the passing step.

91. The method of claim 90, wherein: The viscous material is pre-filtered through a first pre-filter device and then through a second pre-filter device.

92. The method of claim 83, wherein: The plurality of pre-filtration devices are selected from the group consisting of: a series of injection devices, an injection-type syringe, a drain system, an injection device with a Luer lock connector, a compressible tube, a non-compressible tube, a cylinder, or a large syringe.

93. The method of claim 91, wherein: The plurality of pre-filtering devices are a series of injection devices, syringe-type syringes or large syringes, wherein the first pre-filtering device has a larger pore size than the second pre-filtering device.

94. The method of claim 91, wherein: The pore size of the first pre-filtering device is selected from 18G to 34G.

95. The method of claim 91, wherein: The pore size of the second pre-filtering device is selected from 18G to 34G.

96. The method of claim 83, wherein: The viscous material is passed through the at least one filter / screen having a pore size / aperture size smaller than the size of individual particles of the viscous material.

97. The method of claim 83, wherein: The pore size of the at least one filter / mesh is in the range of 1 μm to 1000 μm, and the individual particle size is in the range of 20 μm to 1000 μm.

98. The method of claim 83, wherein: The pore size of the at least one filter / mesh is in the range of 25 μm to 500 μm, and the individual particle size is in the range of 40 μm to 500 μm.

99. The method of claim 83, wherein: The pore size of the at least one filter / mesh is in the range of 50 μm to 200 μm, and the individual particle size is in the range of 75 μm to 200 μm.

100. The method of claim 83, wherein: The filtered viscous material collected in the second collection container is dispensed / injected using a dispensing device.

101. The method according to claim 100, wherein: The filtered viscous material will not clog the dispensing device when being dispensed / injected from the dispensing device.

102. The method of claim 100, wherein: The filtered viscous material has a substantially uniform or controlled extrusion profile when dispensed / injected from the dispensing device.

103. The method of claim 102, wherein: The filtered viscous material is dispensed / injected from the dispensing device after an initial characteristic burst / rupture force without any pressure build-up.

104. The method of claim 103, wherein: The individual particles of the viscous material have an intact morphology.

105. The method of claim 83, wherein: The filtered viscous material triggers a desired immune response in the patient following administration.

106. The method of claim 100, wherein: The dispensing device is selected from the group consisting of: a series of injection devices, an injection-type syringe, an ejection system, an injection device with a Luer lock connector, a compressible tube, a non-compressible tube, a cylinder or a large syringe.

107. The method of claim 83, wherein: The dispensing device is a syringe, wherein the syringe has a needle size of 18G to 34G.

108. The method of claim 83, wherein: The at least one filter / mesh is selected from the group consisting of: a nylon mesh, a stainless steel mesh, a polytetrafluoroethylene mesh, or a nitrocellulose mesh.

109. The method of claim 83, wherein: The at least one filter / screen is placed inside, outside, adjacent to or screwed onto the first collecting container.

110. The method of claim 83, wherein: The at least one filter / screen is replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer or a screening channel.

111. The method of claim 83, wherein: The passing step sizes the individual particles of the viscous material to produce a substantially uniform or controlled particle matrix for ease of administration.

112. The method of claim 83, wherein: The at least one filter / screen is arranged in a Luer lock connector assembled in the first collecting container / a Luer lock connector part of the first collecting container.

113. The method according to claim 112, wherein: The viscous material is forced under / by applying pressure through the at least one filter / mesh disposed within the Luer lock connector portion.

114. The method of claim 113, wherein: The pressure is applied using a plunger, an extruder, a manual compressor, a syringe pump, a platen compressor, rollers for flexible tubing, a compressor, or a device capable of employing a similar mechanism.

115. The method of claim 113, wherein: The pressure is applied using a plunger or an extruder.

116. The method of claim 83, wherein: The passing step is repeated using multiple filters / screens.

117. The method of claim 116, wherein: The multiple filters / screens may be of the same size or of different sizes.

118. The method of claim 116, wherein: The size of the at least one filter / mesh is in the range of 1 μm to 1000 μm.

119. The method of claim 116, wherein: Passing the material through a plurality of filters / screens reduces the viscosity of the viscous material or adjusts the particle size distribution of the viscous material to a desired level, preferably in the range of 50 μm to 750 μm.

120. The method of claim 119, wherein: The method reduces the extrusion force required to inject the viscous material from the extrusion system.

121. The method of claim 83, wherein: The viscous material is selected from the group consisting of: dermal fillers; sealants; adhesives; composite mixtures of mammalian cells; scaffold materials; bone paste; bone cement; cartilage biomaterials; Injectables include those for venous stasis applications; protein hydrogels; carbohydrate hydrogels including cellulose, pectin, and lignin; cell material mixtures; thickeners; gelling agents; and stabilizers.

122. The method of claim 83, wherein: The first collection container is a series of containers with different sizes, a storage unit or chamber, an industrial mixer, an industrial dispenser, an intermediate transfer container, an injection syringe, a large injection syringe, a Luer lock connector device, a discharge system or a compressible tube.

123. The method of claim 83, wherein: The second collection container is selected from at least one of the following: a transfer container, a storage bottle, an injection syringe, a filler cartridge, a series of containers with different sizes, a storage unit or chamber, an industrial mixer, an industrial dispenser, an intermediate transfer container, a large injection syringe, a Luer lock connector device, a discharge system or a compressible tube.

124. The method of claim 123, wherein: The second collection container is used to dispense / inject the filtered viscous material for administration to the patient.

125. The method of claim 83, wherein: The first collection container has a volume greater than that of the second collection container.

126. Use of the method according to any one of claims 1 to 41 or 83 to 125 for reducing the viscosity of a viscous material or adjusting the particle size distribution of the viscous material to a desired level, preferably in the range of 50 μm to 750 μm.

127. Use of the method according to claims 42 to 82, for reducing the viscosity of a dermal filler material or adjusting the particle size distribution of the dermal filler material to a desired level, preferably in the range of 50 μm to 750 μm.

128. Use of a method according to any one of claims 1 to 41 or 83 to 125 for breaking up agglomerates / aggregates in a viscous material.

129. Use of the method according to claims 42 to 82 for breaking down agglomerates / aggregates in dermal filler materials.

130. Use of the method of any one of claims 1 to 41 or 83 to 125 to prevent needle clogging of an injection or dispensing device during delivery of a viscous material.

131. Use of the method of claims 42 to 82 to prevent needle clogging of an injection or dispensing device during delivery of a dermal filler material.

132. Use of the method according to any one of claims 1 to 41 or 83 to 125 for sizing the individual particles of a viscous material such that the viscous material has an almost / substantially uniform individual particle size.

133. Use of the method according to claims 42 to 82 for sizing the individual particles of a dermal filler material such that the dermal filler material has an almost / substantially uniform individual particle size.

134. Use of the method of any one of claims 1 to 41 or 83 to 125 for reducing the individual particle size of a viscous material without affecting / impacting the rheological properties of the viscous material.

135. Use of the method according to any one of claims 1 to 41 or 83 to 125 for reducing the size of the individual particles of viscous material without affecting / impacting / changing the characteristic characteristics or morphology of the individual particles of the viscous material.

136. Use of the method according to claims 42 to 82 for reducing the individual particle size of a viscous material without affecting / impacting the rheological properties of the viscous material.

137. Use of the method according to any one of claims 42 to 82 for reducing the size of the individual particles of viscous material without affecting / impacting / changing the characteristic characteristics or morphology of the individual particles of the viscous material.

138. Use of the method of any one of claims 1 to 41 or 83 to 125 for filtering a viscous material so that the viscous material has a uniform or controlled particle matrix for ease of administration.

139. Use of the method according to claims 42 to 82 for filtering a dermal filler material such that the dermal filler material has a uniform or controlled particle matrix for ease of administration.

140. Use according to the method of any one of claims 1 to 41 or 83 to 125, wherein The viscous material is selected from the group consisting of: dermal fillers; sealants; adhesives; composite mixtures of mammalian cells; scaffold materials; bone pastes; bone cements; cartilage biomaterials; injectables including for venous stasis applications; protein hydrogels; carbohydrate hydrogels including cellulose, pectin and lignin; cellular material mixtures; thickeners; gelling agents; and stabilizers.

141. Use of the method according to any one of claims 1 to 41 or 83 to 125 for reducing the individual particle size of the viscous material, thereby reducing the extrusion force required to inject the viscous material from the extrusion system.

142. Use of the method according to any one of claims 42 to 82 for reducing the individual particle size of the dermal filler material, thereby reducing the extrusion force required to inject the dermal filler material from the extrusion system.

143. An apparatus for removing agglomerates of individual particles from a viscous material, comprising: Extrusion system; as well as At least one filter / screen is placed inside, outside, adjacent to or screwed onto the extrusion system; wherein passing the viscous material through the at least one filter / screen removes agglomerates of individual particles from the viscous material.

144. The apparatus of claim 143, further comprising an extruder for forcing the viscous material through the at least one filter / screen under / by applying pressure.

145. The apparatus of claim 144, wherein: The extruder pressure was regulated by electronic means.

146. The apparatus of claim 142, wherein: The at least one filter / mesh is selected from the group consisting of: nylon, stainless steel, polytetrafluoroethylene or nitrocellulose.

147. The apparatus of claim 142, wherein: The at least one filter / screen is a nylon mesh or a stainless steel mesh.

148. The apparatus of claim 142, wherein: The at least one filter / screen is replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer or a screening channel.

149. The apparatus of claim 148, wherein: The size of the inline filter or the sieving channel is in the range of 0.5 mm to 2540 mm.

150. The apparatus of claim 142, wherein: The extrusion system is connected to a plurality of pre-filtering devices to pre-filter the viscous material prior to passing the material through the at least one filter / screen.

151. The apparatus of claim 150, wherein: The extrusion system is connected to at least one pre-filtration device and a loading container / transfer syringe, wherein the at least one pre-filtration device is connected to the loading container / transfer syringe.

152. The apparatus of claim 142, wherein: The extrusion system is coupled to the loading container / transfer syringe to collect the filtered viscous material.

153. The apparatus of claim 142, wherein: The at least one filter / mesh has a pore size that is smaller than an individual particle size of the viscous material.

154. The apparatus of claim 142, wherein: The at least one filter / mesh has a pore size in the range from 1 μm to 1000 μm, and the individual particle size is in the range of 20 μm to 1000 μm.

155. The apparatus of claim 142, wherein: The at least one filter / mesh has a pore size in the range from 25 μm to 500 μm, and the individual particle size is in the range of 40 μm to 500 μm.

156. The apparatus of claim 142, wherein: The at least one filter / mesh has a pore size in the range from 50 μm to 200 μm, and the individual particle size is in the range of 75 μm to 200 μm.

157. The apparatus of claim 142, wherein: The extrusion system is selected from the group consisting of an injectable syringe, an expulsion system, a Luer lock connector device, or a compressible tube.

158. The apparatus of claim 142, wherein: The extrusion system is a syringe.

159. The apparatus of claim 158, wherein: The syringes have needle sizes ranging from 18G to 34G.

160. The apparatus of claim 142, wherein: The loading container / transfer syringe is selected from the group consisting of an injection-type syringe, an ejection system, a Luer lock connector device, or a compressible tube.

161. The apparatus of claim 142, wherein: The loading container / transfer syringe is a syringe.

162. The apparatus of claim 161, wherein: The syringes have needle sizes ranging from 18G to 34G.

163. The apparatus of claim 142, wherein: The volume of the extrusion system is greater than the volume of the loading container / transfer syringe, or wherein the extrusion system has a lower cross-section than the loading container / transfer syringe.

164. The apparatus of claim 142, wherein: The extrusion system is a Luer lock connector injection device.

165. The apparatus of claim 164, wherein: The at least one filter / screen is disposed within the Luer lock connector.

166. An apparatus for removing agglomerates of individual particles from a viscous material, comprising: a first collection container; at least one filter / screen mounted inside, outside, adjacent to or screwed onto the first collection container; wherein passing the viscous material through the at least one filter / screen removes agglomerates of individual particles from the viscous material; as well as A second collecting container is coupled to the first collecting container for collecting the filtered viscous material.

167. The apparatus of claim 166, wherein: The first collecting container comprises an extrusion system according to claims 143 to 165.

168. The apparatus of claim 166, wherein: The first collection container is selected from the group consisting of: a series of containers with different sizes, storage units or chambers, industrial mixers, industrial dispensers, intermediate transfer containers, injection syringes, large injection syringes, Luer lock connector devices, discharge systems or compressible tubes.

169. The apparatus of claim 166, wherein: The second collection container is selected from the group consisting of a transfer container, a storage bottle, an injection syringe, a filler cartridge, a series of containers with different sizes, a storage unit or chamber, an industrial mixer, an industrial dispenser, an intermediate transfer container, a large injection syringe, a Luer lock connector device, a discharge system or a compressible tube.

170. The apparatus of claim 166, wherein: An additional filter / screen is fitted in the second collecting container.

171. The apparatus of claim 166, wherein: The second collecting container is a collecting chamber disposed within the first collecting container.

172. The apparatus of claim 166, wherein: The apparatus further comprises an extruder for forcing the viscous material through the at least one filter / screen under / by applying pressure.

173. The apparatus of claim 1, wherein: The extruder pressure was regulated by electronic means.

174. The apparatus of claim 166, wherein: The at least one filter / mesh has a pore size in the range from 1 μm to 1000 μm, and the individual particle size is in the range of 20 μm to 1000 μm.

175. The apparatus of claim 166, wherein: The at least one filter / mesh has a pore size in the range from 25 μm to 500 μm, and the individual particle size is in the range of 40 μm to 500 μm.

176. The apparatus of claim 166, wherein: The at least one filter / mesh has a pore size in the range from 50 μm to 200 μm, and the individual particle size is in the range of 75 μm to 200 μm.

177. The apparatus of claim 167, wherein: The at least one filter / mesh is selected from a nylon mesh, a stainless steel mesh, a polytetrafluoroethylene mesh or a nitrocellulose mesh.

178. The apparatus of claim 166, wherein: The at least one filter / screen is replaced with an inline filter, a gated impeller, a static mixer, a high shear mixer, a viscous mixer or a screening channel.

179. The apparatus of claim 166, wherein: The first collection container is connected to a plurality of pre-filtering devices to pre-filter the viscous material prior to passing the material through the at least one filter / screen.

180. The apparatus of claim 166, wherein: The first collecting container is connected to a plurality of pre-filtering devices, and the pre-filtering devices are connected to the second collecting container.

181. The apparatus of claim 166, wherein: The first collecting container is connected to a first pre-filtering device and a second pre-filtering device, and the pre-filtering device is connected to the second collecting container.

182. The apparatus of claim 166, wherein: The at least one filter / mesh has a pore size that is smaller than an individual particle size of the viscous material.

183. The apparatus of claim 166, wherein: A Luer lock connector is fitted into the first collecting container.

184. The apparatus of claim 183, wherein: The at least one filter / screen is placed inside the Luer lock connector assembled within the first collection container.

Images