Fluid mixing device and mixing method

Abstract

To provide a mixer (1) and a fluid mixing method by successive transfer between syringes.SOLUTION: A mixing method includes the following steps of: arranging a pair of syringes (2, 3) in a mixer (1); adjusting variable fixing elements adaptable to the pair of syringes (2, 3); and selecting and performing a mixing problem which can adjust a mixing force, speed and range, and conveying frequency. A mixer is provided with a movable conveyor cart (7) movable in a longitudinal direction and fixing elements (8, 9) a distance between which is adjustable. This makes it possible to mix or emulsify blood fluid of different viscosity, especially protein gel and platelet-rich plasma, and to versatilely, sanitarily and effectively adjust dermatological formulations.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present invention is in the field of laboratory equipment, in particular biological fluid mixing equipment. The present invention relates to a mixing device that allows rapid and reproducible mixing or emulsification of biological fluids, for example autologous fluids obtained from the plasma of a patient. The present invention also relates to a method of mixing biological fluids to obtain a formulation for topical or injectable administration. [Background technology]

[0002] Currently, there are techniques and equipment used in laboratories or beauty clinics to obtain autologous fluids extracted from the patient's blood, such as platelet-rich plasma gel. For this purpose, centrifugation equipment can be used that allows the separation of the different components of the patient's blood for later use. One example of the use of compositions made from the patient's plasma is skin or beauty treatment. There are protocols for obtaining plasma gel, which is then used by intradermal injection for the removal of facial wrinkles. These protocols are usually based on fractionation of the patient's blood by centrifugation, followed by further processing by a clinical specialist before the final product is injected into the patient.

[0003] Once the fluids are extracted from the blood, they must be precisely mixed or emulsified to obtain the commercial product or final formulation that is delivered to the patient. Syringes of various sizes containing the emulsified or dispensed product can be used for both pre-emulsification and delivery to the patient.

[0004] There are also various infusion pumps on the market to control the delivery of the syringe contents. US Pat. No. 5,399,433 discloses an example of an infusion pump adapted for use with the syringe of the present invention, based on a motor system that controls the movement of the carriage carrying the syringe relative to the casing for delivery of the syringe fluid to the patient. The device as described in US Pat. No. 5,399,433 does not provide a solution for accurate emulsification of the product before administration to the patient.

[0005] Moreover, known protocols for this type of application suffer from a certain lack of reproducibility of the resulting product and from undesirable over-processing, which may cause undesirable contamination of the product ultimately delivered to the patient. To try to overcome these limitations, there are mixing devices that allow for automatic or semi-automatic emulsification of fluids, facilitating the preparation of a formulation that can be delivered immediately, without the need to emulsify or mix the fluids manually. These devices allow the transfer of contents between two facing syringes and allow for configurable parameters such as the adjustment of the mixing speed. However, they are usually designed specifically for a certain size of syringe, which generally limits their versatility. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2016 / 077538 [Patent Document 2] Spanish Patent No. 2633815 Summary of the Invention [Problem to be solved by the invention]

[0007] It is an object of the present invention to provide a device that allows efficient mixing or emulsification of plasma components and offers several improvements in terms of versatility of the mixing procedure. [Means for solving the problem]

[0008] The object of the present invention is a method and a mixing device for mixing or emulsifying fluids by successive transfer between syringes having a certain transfer range. The mixing device according to the invention comprises at least one mobile carriage movable in the longitudinal direction and equipped with a casing adapted to accommodate and hold at least a pair of syringes. These syringes are connected to each other facing each other and connected to each other by a first end of each syringe and arranged in alignment. The mixing device further comprises at least two fixing elements, one on each side of the mobile carriage and adapted to accommodate and hold the second free end of each syringe. At least one of the fixing elements is adjustable and adapted to accommodate and hold the free end of the corresponding syringe in a movable position along the longitudinal direction. In this way, the distance between the two fixing elements can be variably adjusted. To execute the transfer program, the mixing device comprises a control unit, which communicates with a set of sensors and with a mechanism for the transmission of a linear movement to the mobile carriage triggered by a control signal generated by the control unit. The set of sensors comprises a calibration sensor for automatic calibration of the range of each transfer and at least one reversal sensor allowing reversal of the displacement direction of the movable carriage.

[0009] Like some known mixing devices, the device of the present invention makes it possible to mix, emulsify and / or homogenize components present in a fluid, preferably the blood of a patient, by transferring the fluid between a pair of connected syringes. However, compared to existing devices, the mixing device according to the present invention offers significant versatility from several points of view.

[0010] On the one hand, the device allows to adjust various parameters such as the power of the internal motor according to the viscosity of the fluids to be mixed, the number of transfers and the adjustable speed of transfers according to a pre-set program. The fact of allowing an automatic and universally configurable mixture or emulsion makes it possible to obtain a final product with the appropriate viscosity, applicability and biomechanical properties of the tissue, regardless of the clinical expert who makes the mixture or emulsion. The mixing device according to the invention thereby greatly facilitates the manufacturing procedure of the final product, shortening the preparation time and eliminating variability due to the clinical expert involved.

[0011] The mixing device of the present invention allows the mixing or emulsification of fluids extracted from a patient's blood, in particular protein gel and platelet rich plasma, for the production of products or formulations. These fluids, when mixed using the device of the present invention, can be administered topically or by subcutaneous or intradermal injection, for example for the treatment of different types of facial wrinkles. Although the mixing device of the present invention is specifically designed to mix blood compounds extracted from a patient's blood, the mixing device can be used for the emulsification or mixing of other types of fluids that require similar properties.

[0012] The mixing device of the present invention is compatible with standard syringes of different sizes, for example with volumes between 1 ml and 60 ml from different manufacturers. Furthermore, due to the adjustable configuration of the fixing element, the mixing device of the present invention has a very advantageous feature in the sense that it allows for variable loading or variable filling levels of the syringes. This variability in terms of the mixing volume is particularly advantageous when mixing variable blood components depending on the patient's blood type.

[0013] The mixing method according to the present invention includes the steps of loading at least a pair of syringes facing each other with the fluids to be mixed, placing the pair of syringes in the mixing device, adjusting the position of an adjustable fixing element and fixing the pair of syringes to the fixing element, selecting a mixing program including a predefined number of transfers with variable and predetermined speeds for each transfer, and executing the selected mixing program.

[0014] The present invention allows the mixing of autologous fluids with different viscosities. According to a preferred embodiment of the present invention, the mixed fluids are protein gel and activated plasma, both obtained from the patient's blood. In summary, the mixing device and the mixing method according to the present invention provide an optimal emulsion of two different plasma components obtained from the patient's own blood, due to the fact that the mixing device has a flexible configuration that allows adjusting the high mechanical forces required for the accurate homogenization of fluids of different viscosities such as the aforementioned protein gel (solid phase) and activated plasma (liquid phase). This makes the mixing device of the present invention an important instrument for the preparation of topical or injectable formulations.

[0015] The precise mixing of both components results in a 100% autologous and extemporaneously prepared product or formulation. The invention has further advantages in terms of hygiene and sterility, since the mixed product can be directly used for treatment, e.g. skin treatment, by injecting the product directly into the patient with one of the syringes used in the mixing device. In this way, additional transfers of the final product are avoided, minimizing the possibility of contamination and keeping the product sterile.

[0016] In the present invention, a mixed fluid may contain a liquid phase, a substance, or cells in suspension. The result of the mixing operation of two fluids is an emulsion, where one fluid is dispersed in another. Therefore, the term mixing should also be understood in a broad sense and includes the concepts of emulsification and / or homogenization.

[0017] Details of the invention can be seen in the accompanying drawings, without limiting the scope of the invention. [Brief description of the drawings]

[0018] [Figure 1] 1 shows a perspective view of an embodiment of a mixing device according to the present invention. [Diagram 2] FIG. 2 shows a perspective view of the mixing device of FIG. 1 with two pairs of syringes. [Diagram 3] 2 shows an exploded plan view of the external components of the mixing device of FIG. 1. [Figure 4] FIG. 2 is a block diagram showing the electromechanical operation of the mixing device of FIG. 1. [Diagram 5] 2 shows a detailed plan view illustrating the operation of an adjustable fixing element of the mixing device of FIG. 1. [Figure 6] 2 shows a detailed plan view illustrating the operation of an adjustable fixing element of the mixing device of FIG. 1. [Figure 7] 2 shows a detailed plan view illustrating the operation of an adjustable fixing element of the mixing device of FIG. 1. [Figure 8] 2A-2C show plan views illustrating the operation sequence of the mixing device of FIG. 1 when half of a transfer between a pair of syringes having a first size is performed. [Figure 9] 2A-2C show plan views illustrating the operation sequence of the mixing device of FIG. 1 when half of a transfer between a pair of syringes having a first size is performed. [Figure 10] 2A-2C show plan views illustrating the operation sequence of the mixing device of FIG. 1 when half of a transfer between a pair of syringes having a first size is performed. [Figure 11] 2A-2C are plan views showing the sequence of operation of the mixing device of FIG. 1 when a portion of a transfer between a pair of second, smaller sized syringes is performed. [Figure 12] 2A-2C are plan views showing the sequence of operation of the mixing device of FIG. 1 when a portion of a transfer between a pair of second, smaller sized syringes is performed. [Figure 13] 2A-2C are plan views showing the sequence of operation of the mixing device of FIG. 1 when a portion of a transfer between a pair of second, smaller sized syringes is performed. [Figure 14] An example of a test tube of blood after centrifugation, resulting in a mixed fluid, is shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] The object of the present invention is a mixing device and method for efficiently and reproducibly mixing, emulsifying and / or homogenizing two or more fluids. The fluids to be mixed are transferred between a pair of syringes, which are connected face-to-face to each other and placed in a mixing device (1) according to the invention. For the sake of greater clarity, the definition of transfer is explained in detail below.

[0020] A perspective view of an embodiment of the mixing device (1) of the present invention is shown in Figure 1. Figure 2 shows the position of two pairs of facing syringes (2, 3) in the mixing device (1) of Figure 1. In the normal usage of the mixing device (1), only a pair of facing syringes is usually used, i.e., two syringes (2) with a certain volume or two syringes (3) with a smaller volume.

[0021] Each syringe (2, 3), an element known in the prior art, comprises a tubular body or cylinder (2b, 3b), which is provided with a hole in an injection zone (2c, 3c) located at one end of the respective syringe (2, 3) to allow the intake and discharge of fluids into and from the cylinder (2b, 3b). This end is usually engaged with a hollow needle or connector. By joining them at their ends, it is possible to connect two opposing syringes (2, 3) to allow the transfer of fluids between both syringes (2, 3), as shown in FIG. 2. Each syringe (2, 3) comprises a plunger that is longitudinally movable along the inside of the cylinder (2b, 3b). The plunger has a support or handle (2a, 3a) at its free end to facilitate its displacement, and also comprises a composite piston located inside the cylinder (2b, 3b) and at the end opposite the handle (2a, 3a). The syringes (2, 3) are usually transparent and can be made of a variety of materials such as plastic, glass or metal. In the medical field, sterile plastic syringes suitable for medical use are usually used.

[0022] FIG. 3 shows a schematic exploded plan view of the external components of the mixing device of FIG.

[0023] As shown in the drawings, the mixing device (1) comprises at least one movable carriage (7) movable in a longitudinal direction (6), the movable carriage (7) having a general recess or cavity (7a) configured to receive and hold at least a pair of facing syringes (2, 3), which are joined to each other by connecting elements (4) at the injection zones (2c, 3c) and aligned in the longitudinal direction (6), as shown in FIG.

[0024] In the present invention, the definition of a transfer should be understood as a complete transfer of fluids mixed between two pairs of opposing syringes (2, 3) by a complete forward or backward displacement of the plungers (2e, 3e) of the syringes (2, 3). A transfer cycle should be understood as the sum of a forward transfer and a backward transfer (i.e. two transfers). The extent of a transfer cycle is the distance traveled by the movable carriage (7) in each transfer and varies depending on the size of the syringes (2, 3).

[0025] Furthermore, the mixing device (1) comprises at least two fixing elements (8, 9), each located on a side of the mobile carriage (7). Each of the fixing elements (8, 9) is configured or adapted to receive and hold the free end of one of the syringes (2, 3).

[0026] In the embodiment of Figures 1 and 2, the mixing device (1) comprises a casing (5) which houses and supports the various components of the mixing device (1). The mobile carriage (7) and the fixing elements (8, 9) are supported on the upper surface (5a) of the casing (5) by known fixing elements (e.g. screws or other alternative fixing means, not shown in the drawings). The casing (5) further integrates a set of signal and control elements (17, 18, 19, 20). The casing (5) further houses a set of electrical and mechanical components necessary for the correct operation of the device. The construction of the casing (5) is not particularly relevant to the present invention, since its parts, manufacturing materials and dimensions may vary, provided that it is suitable for laboratory use and fully performs its function of housing the components of the mixing device (1) and enabling its correct operation.

[0027] The mixing device (1) of the present invention comprises a control unit (11) in communication with a set of sensors (15, 16) and a mechanism (13, 14) for transmitting linear motion to the movable carriage (7), the transmission being triggered by a control signal generated by the control unit (11). A block diagram of the electronic components of an embodiment of the mixing device (1) corresponding to FIG. 1 is shown in FIG. 4. As shown in FIG. 4, the mixing device (1) comprises a 24V DC power supply (10). The control unit (11) comprises a memory having a set of predefined or configurable programs for controlling the operation of the mixing device (1). The mechanism (13, 14) housed within the casing (5) comprises a motor (13) and a mechanical drive shaft (14). In the particular embodiment of the drawings, the mixing device (1) optionally uses a stepper motor (13). The control unit (11) generates a pulse signal (12) that controls the rotation of the motor (13). For every 200 pulses, the stepper motor (13) rotates one revolution. The rotation of the motor (13) is transmitted to a mechanical shaft (14) that is engaged with the motor (13). The drive shaft (14) connected to the movable carriage (7) converts the rotational motion of the motor (13) into linear motion. For each rotation of the motor (13), the drive shaft (14) moves the movable carriage (7) 15 mm.

[0028] The set of sensors (15, 16) comprises a calibration sensor (15) for automatic calibration of the range of each transfer. This calibration sensor (15) detects the approach of the mobile carriage (7) and sends a signal to the control unit (11), which changes the direction of travel of the mobile carriage (7). In this way, the electronics of the mixing device (1) determine the maximum range of the transfer cycle based on the loading or percentage of the initial variable filling of the syringe (2). This initial adjustment is called calibration. Optionally, the calibration sensor (15) comprises a limit switch located on one of the fixed elements (8, 9) and a screw located on the mobile carriage (7) for initial automatic calibration. In alternative embodiments of the invention, other types of mechanical or electronic sensors can be used. The mixing device (1) also includes at least one reversal sensor (16), also in communication with the control unit (11), for reversing the direction of travel of the mobile carriage (7).

[0029] In the mixing device (1) of the present invention, at least one of the fixing elements (9) has an adjustable configuration. By "adjustable" it is understood that the fixing element (9) is adapted to accommodate, hold and fix the free end of one of the syringes (2, 3) in an initial position movable along the longitudinal direction (6). In this way, the distance between the two fixing elements (8, 9) can be variably adjusted. This particular feature of the mixing device (1) is highly advantageous since it allows the accommodation of syringes (2) with variable volumes or filling levels while maintaining a proper fixation of the handle (2a) of the plunger (2e) of the syringe (2) in both fixing elements (8, 9). It also allows the mixing device (1) to be compatible with syringes (2, 3) of different lengths and sizes, which increases the versatility of the mixing device (1) in particular.

[0030] In the particular embodiment of the drawings, the mixing device (1) comprises in particular a non-adjustable fixing element (8) and an adjustable fixing element (9). Other embodiments are conceivable in which both fixing elements (8, 9) are adjustable.

[0031] Figures 5 to 7 show the operation of an embodiment of the adjustable fixing element (9). Optionally, the adjustable fixing element (9) comprises a fixed part (9f) and a movable part (9d) in the longitudinal direction (6). Also optionally, the fixing elements (8, 9) can have a modular configuration with one or more auxiliary parts (8s, 9s) that can be assembled together and / or connected to the fixing element (9). In the embodiment of the figures, the fixing element (9) comprises both configurations, i.e. parts (9f, 9d) and the possibility of incorporating an auxiliary part (9c) to allow the adjustment of a variable distance between both fixing elements (8, 9), as shown in Figures 11 to 13, allowing a proper fit and fixation of syringes (2, 3) of variable sizes or filling levels.

[0032] Furthermore, the fixing elements (8, 9) may comprise different mechanisms known in the prior art, such as rails, slots, fixing screws, or other elements. The fixing elements (8, 9) can be made of one or more pieces of any resistant material suitable for use with laboratory materials.

[0033] Optionally, the casing (5), the mobile carrier (7) and the fixed elements (8, 9) can be made of metal.

[0034] Optionally, as in the embodiment of the drawings, the housing (7a) of the mobile carrier (7) includes a number of cavities extending along the longitudinal direction (6) and allowing the accommodation, retention and fixation of the cylinders (2b, 3b) of the syringes (2, 3) in a position parallel to the longitudinal direction (6). These cavities (7b) can be seen in more detail in FIG. 3. The described embodiment includes in particular four semi-cylindrical cavities (7b), the diameter of which is adjusted to the diameter of the syringes (2, 3), in this case to accommodate a first pair of syringes (2) of 20 ml and a second pair of syringes (3) of 3 ml. An intermediate space (7c) adapted to accommodate a connecting element (4) between the pairs of syringes (2, 3) is arranged between each pair of semi-cylindrical cavities (7b).

[0035] Optionally, the fixing element (8, 9) comprises a housing (8a, 9a) having a semi-cylindrical portion (8b, 9b) and provided with a slot (8c, 9c) adapted to fit and hold the handle (2a, 3a) at the free end of the syringe (2, 3).

[0036] The elements described for the mixing device (1) enable proper mating and fixation of the pair of facing syringes (2, 3) so that mixing of the fluids can be accurately performed and prevents unwanted ingress of air into the mixture and / or the formation of unwanted bubbles and bubbles.

[0037] The general operation of the mixing device (1) is described below. Preliminarily, a protocol is carried out to obtain the fluids to be mixed, as will be explained in more detail in some examples contained later in this specification. Figures 8, 9 and 10 show a schematic diagram of a half-sequence of transfer between a pair of 20 ml syringes (2). Before switching on the mixing device (1), the fluid to be mixed or emulsified is placed in the first syringe (2). The second empty syringe (2) is connected face-to-face to the filled syringe (2) by the aligned connecting means of the pair of syringes (2) facing each other by their injection zones (2c) using an intermediate connecting element (4). The connecting element (4) between the pair of facing syringes (2) can be of the Luer-to-Lure type as in the embodiment of the figures, but other types of connecting elements (4) are also possible. Once the two syringes (2) are connected, as shown in Fig. 8, they are placed in the mixing device (1), with their respective cylinders (2b) fixed to the mobile carriage (7) and the handles (2a) of the plungers (2e) inserted into the slots (8c, 9c) of the fixing elements (8, 9). If necessary, the position of the adjustable fixing element (9) is adjusted according to the length of the loaded syringes (2) and / or the level of loading or initial filling. The desired program is then selected by means of the push buttons or controls (18, 19, 20) of the casing (5). The start of the selected program, previously programmed or configured in the internal memory of the control unit (11), is activated, for example, by the start-stop push button (17). Each program carries out a predefined number of transfers at a given speed. A control unit (11) generates a pulse signal (12) for a stepper motor (13), and a drive shaft (14) converts the rotational motion of the motor (13) into a linear motion that is transmitted to the movable carriage (7). The cylinders (2b) of the syringes (2) move along the longitudinal direction (6) simultaneously with the movable carriage (7). Similarly, the plungers (2e) of both syringes (2), fixed to the fixed elements (8, 9), slide internally and longitudinally along the cylinders (2b) as the movable carriage (7) moves. With each transfer (forward and backward transfer), the contents of the syringes (2) are transferred to the opposite syringe (2) such that one syringe (2) is emptied while the other syringe is filled.The reversal of movement to carry out the continuous programmed transfer is also controlled by the control unit (11) by a motion reversal sensor (16) installed on the fixed element (8) of the mixing device (1). The above described procedure is also similar when using the other pair of syringes (3) of smaller size and caliber depending on the final product to be obtained. Figures 11, 12 and 13 show the positioning and part of the transfer sequence when a syringe (3) of smaller size and auxiliary part (9c) for the adjustment of the syringe (3) are used.

[0038] In the embodiment of the drawings and examples, the opposing syringes are of the same size and caliber (two 20 ml syringes or two 3 ml syringes). Other embodiments of the mixing device (1) are also contemplated in which the mobile carriage (7) accommodates pairs of opposing syringes of different sizes.

[0039] Optionally, the mobile carrier (7) and the fixing elements (8, 9) are removable and replaceable by other mobile carriers and fixing elements, compatible with syringes of different sizes and compatible with each other. This feature makes it possible to configure the mixing device (1) to allow the assembly of pairs of syringes of different sizes without requiring that all carriers and fixing elements are permanently integrated into the mixing device (1). This possibility further increases the versatility of the mixing device (1), even when it is small.

[0040] The mixing device (1) admits of other variations not shown in the embodiment of the drawings. For example, the mixing device (1) may comprise a plurality of movable carriages (7) arranged in parallel. The mixing device (1) may comprise two or more motors (13) for controlling the movement of several movable carriages (7). Other embodiments of the mixing device (1) with movable carriages (7) configured to accommodate three or more pairs of facing syringes are also conceivable. Other configurations of the mixing device (1) with a plurality of movable carriages (7) each accommodating two or more pairs of syringes of the same or different sizes are possible.

[0041] Also optionally, in another alternative embodiment, the single movable carrier (7) has a sliding configuration designed to accommodate syringes with variable sizes. For example, the movable carrier (7) can have several slidable coupling parts depending on the length of the pair of syringes. Optionally, the cavity (7b) of the movable carrier (7) can have an adjustable range to accommodate pairs of syringes with variable calibers. Similarly, the intermediate space (7c) can have a variable configuration to accommodate connecting elements (4) of different configurations.

[0042] Optionally, each movable carrier (7) may be provided with additional auxiliary elements, such as caps, handles or other movable elements that can be opened and closed to improve retention and fixation of the cylinders (2b, 3b) of the syringes (2, 3) and to prevent displacement of the cylinders (2b, 3b) during operation of the mixing device (1).

[0043] In the embodiment of the drawings, the casing (5), the mobile carrier (7) and the fixed elements (8, 9) are made of metal, but the materials and the number of parts of the different components of the mixing device (1), the casing (5), the mobile carrier (7) and the connecting elements (8, 9) can be changed as long as they are compatible with the function of the mixing device (1).

[0044] The casing (5) may optionally include a number of buttons, selectors, displays or display interfaces, and a communication system for monitoring the operation of the mixing device (1). The mixing device (1) may also have an optional lid or cover.

[0045] Various detailed optional features demonstrate the great versatility of the mixing device (1) of the present invention, which allows for multiple configurations or variations, as long as they ensure the correct alignment between the movable carriage (7) and the fixed elements (8, 9) to allow for proper accommodation of the syringes (2, 3) so that the fluids are mixed correctly and tensions that may cause undesirable effects such as breaking the syringes (2, 3) or cutting them off are prevented.

[0046] The invention also relates to a method for mixing fluids by successive transfers between syringes with a specific range of transfers, using the mixing device according to the invention, to obtain a final product to be administered to a patient. The mixing method comprises the steps of loading at least a pair of facing syringes (2, 3) with the fluids to be mixed, placing the pair of syringes (2, 3) in the mixing device (1) and fixing their respective cylinders (2b) to a mobile carriage (7), adjusting the position of the adjustable fixing element (9) depending on the size and / or loading of the syringes (2, 3), fixing the handles (2a, 3a) to the fixing elements (8, 9), and selecting and executing a mixing program including a predefined number of transfers with variable and predefined speeds for each transfer. After the execution of the program is completed, the pair of syringes (2, 3) is removed.

[0047] The invention also relates to the products obtained by this mixing process and to the use of these products for medical or dermatological purposes, in particular for the treatment of facial or other types of wrinkles.

[0048] Example of a method according to the invention The method of the present invention allows the execution of different programs which can be pre-programmed or set by the user.

[0049] Three non-limiting examples of the method according to the invention are described below to obtain three different dermatological products. For this purpose, the mixing device (1) of the embodiment of FIG. 1 can be used, equipped with a mobile carriage (7) in which two pairs of syringes (2) of 20 ml or two pairs of syringes (3) of 3 ml can be accommodated, respectively, as detailed above. The mixing device (1) of this embodiment has in particular three predefined programs for obtaining three different final products to be administered to the patient, namely a subcutaneous gel, an intradermal gel or a serum for topical administration. For each of these products, three phases are described, a first phase or protocol for obtaining the fluid to be mixed, a second phase constituting the mixing itself, and a third phase of the administration of the product. The three examples use the mixing device of the invention for an optimal emulsion of two different plasma components obtained from the patient's blood, namely a protein gel and a liquid platelet extract (supernatant). The precise mixing of both components by the device and method according to the invention allows a formulation to be obtained with in situ preparation in a 100% autologous manner.

[0050] Example 1: Method for making subcutaneous gel using a pair of 3 ml syringes according to Program 1. Phase 1: Protocol for obtaining mixed fluids This includes the following steps: 1. Extraction of blood from the patient. The blood sample is subsequently stored in tubes to obtain the required plasma fraction. 2. Centrifugation to separate blood into the following components (see Figure 14) · Growth factor-rich plasma: The plasma columns (F1, F2) contain a large proportion of platelets distributed according to an increasing concentration gradient, with the number of platelets being low at the top of the tube and high towards the bottom of the tube. · White blood cells or leukocytes: These are a thin, whitish layer that is deposited just above the red blood cells. · Red blood cells: the column that occupies the bottom of the tube. 3. Fractionation: This involves the extraction of plasma in two tubes (T1, T2) by means of a suction device, e.g. BTI® Plasma Transfer Device 2 (PTD®). A protein gel or gel fraction (FG) is obtained, constituting the mixed solid phase. This gel fraction (FG) is obtained by mixing fractions (F1, F2) of the first tube (T1) with fraction (F1) of the second tube (T2). A volume of 2.5 ml of gel fraction (FG) (F1+F2+F1) is loaded into a 3 ml syringe. A volume of 2 ml of fraction (F2) is then extracted from tube (T2). 4. Preparation of the protein gel (GP), i.e. the solid phase to be mixed. This is done by heating the gel fraction (FG) and leaving it at room temperature. The heating and leaving times are adapted so that the final product is administered subcutaneously (approximately 12 minutes of heating and 5 minutes of leaving). A BTI® Plasmatherm device can be used for heating. 5. Activation of platelets to obtain the liquid phase to be mixed (supernatant): A fraction (F2) of 2 ml volume of plasma extracted from the second tube (T2) is activated with 0.24 ml of PRGF® Endoret® platelet activator and rocked. The platelet activator is intended to release the growth factors contained in the platelets. After activation, the formation and subsequent retraction of a clot in the plasma is allowed to obtain the supernatant. A 3 ml syringe is loaded with 0.5 ml of activated plasma (PA), constituting the liquid phase to be mixed.

[0051] Phase 2: Mixing Both the solid and liquid phases obtained in phase 1 are mixed: 2.5 ml of protein gel (GP) (solid phase) is mixed with 0.5 ml of activated plasma (PA) or platelet extract (liquid phase or supernatant). To this end, phase 2 comprises the following steps: · Manually transfer 0.5 ml of fresh activated plasma (PA) into a syringe containing 2.5 ml of protein gel (GP). Once the full volume is available in the 3ml syringe, a second empty 3ml facing syringe is connected and the pair of syringes is housed in the mixing device (1). To obtain a subcutaneous injectable gel, run Program 1: a pair of 3 ml syringes is used with a fixed range or displacement of 48 mm per transfer. A total of 11 transfers are made with a speed of 300 steps / s or 22.5 mm / s.

[0052] Phase 3: Product Administration The pair of syringes is removed and the empty syringe is disconnected. A needle is then placed into the 3 ml syringe containing the mixed product and the subcutaneous gel is injected into the patient. Subcutaneous penetration of this product can be used for wrinkle filling and volume augmentation.

[0053] Example 2: Method for preparing an intradermal gel using a pair of 3 ml syringes according to Program 2. Phase 1: Protocol for obtaining mixed fluids Steps 1 to 3 are the same as in the previous Example 1. In step 4, the time for preparation of the protein gel (GP) is different from that in the case of intradermal administration (8 minutes of heating and at least 5 minutes of standing).

[0054] Phase 2: Mixing As in example 1, both the solid and liquid phases obtained in phase 1 are mixed. In other words, 2.5 ml of protein gel (GP) (solid phase) is also mixed with 0.5 ml of activated plasma (PA) or platelet extract (liquid phase or supernatant). To this end, phase 2 comprises the following steps: · Manually transfer 0.5 ml of fresh activated plasma into a syringe containing 2.5 ml of protein gel. Once the entire amount is in the 3ml syringe, a second empty 3ml facing syringe is connected and the pair of syringes is placed in the mixing device (1). In this case, program 2 is run to obtain an intradermal injectable gel: a pair of 3 ml syringes with a fixed displacement of 48 mm per transfer is also used. A total of 90 transfers are performed at a speed of 1000 steps / s or 75 mm / s.

[0055] Phase 3: Product Administration This step involves removing the pair of syringes and disconnecting the empty syringe so that the product can be dispensed into three 1 ml syringes for intradermal penetration.

[0056] Example 3: Method for preparing serum using a pair of 3 ml syringes according to Program 1. Phase 1: Protocol for obtaining mixed fluids The method includes the following steps: 1. Draw blood from the patient into TP10 BTI® 9ml collection tubes. 2. Centrifugation for separation of blood components. It is recommended to perform the centrifugation on a BTI® System V instrument without refrigeration of the blood samples for a maximum of 1 hour after extraction. A blood separation containing the three components shown in Figure 14 is obtained. 3. Fractionation: Aspiration of plasma contained in the sample collection tubes by the PTD2 BTI® aspiration unit. Two TP10 BTI® self-empty tubes are filled by aspirating the entire plasma volume, i.e. both fractions (F1, F2) of several centrifuge extraction tubes. The plasma obtained is transferred to a 20 ml syringe. 4. Preparation of protein gel (gelled plasma): To gel a 20 ml syringe of plasma, it needs to be heated for 12 minutes in the Plasmasphere II device and then left to stand following the platelet activation step. 5. Activation of platelets to obtain a mixed liquid phase (supernatant): 0.02 ml of PRGF® Endoret® activator is used for every ml of plasma to be activated. Heat to about 37°C in Plasmasphere II for about 40-60 minutes. WO 02 / 06333, filed by the same applicant as the present invention, discloses in more detail a method for obtaining an autologous engraftment preparation in the form of a cream, based on plasma rich in growth factors.

[0057] Phase 2: Mixing We proceed to mix both the solid and liquid phases obtained in phase 1. For this purpose, the following steps are carried out: · Transfer the entire volume of the supernatant into the 20 ml syringe containing the gelled plasma. Once all of the fluid to be emulsified has been placed into the 20 ml syringe, a second empty 20 ml facing syringe is connected and the pair of syringes is housed in the mixing device (1). · To obtain the topically administered serum, run program 3: a pair of 20 ml syringes with adjustable displacement are used. In this program, the movable carrier (7) on which the 20 ml syringes used in this protocol are placed is adjustable, since the volumes to be mixed are variable and depend on the patient's blood type, but in many cases the range of transfer can be adjusted to about 74 mm. Limit switches are used to calculate the range in an initial calibration cycle. For this purpose, a transfer cycle (two transfers, i.e. forward and backward) is performed at a speed of 300 pulses / s in order to calculate the range. Mixing is then performed. The speed of this program 3 (excluding the above two recognition transfers) is 300 pulses / sec for the first round (2 transfers), 300 pulses / sec for the second round (2 transfers), 450 pulses / sec for the third round (2 transfers), 600 pulses / sec for the fourth round (2 transfers), 750 pulses / sec for the fifth round (2 transfers), 900 pulses / sec for the sixth round (2 transfers), and 1000 pulses / sec for the seventh round and beyond (2 transfers). A total of 120 transfers are performed.

[0058] Phase 3: Product Administration The serum is administered topically. The dispensable serum may be stored in a single dose dispenser or an airless dispenser, preferably at a temperature between 2° C. and 6° C. for long term storage periods prior to administration.

Claims

1. 1. A method for obtaining a final product to be administered to a patient, comprising: loading at least a pair of syringes (2, 3) with the fluids to be mixed; placing said at least one pair of syringes (2, 3) in a mixing device (1), said mixing device (1) comprising at least one mobile carriage (7) movable in a longitudinal direction (6) and comprising a housing (7a) configured to accommodate and hold said at least one pair of syringes (2, 3), said at least one pair of syringes (2, 3) being connected to each other by a first end of each syringe (2, 3) and arranged in said housing (7a) aligned in said longitudinal direction (6), said mixing device (1) comprising at least two fixing elements (8, 9) adapted to accommodate and hold a second free end of each syringe (2, 3), said at least one fixing element (9) having an adjustable configuration and adapted to accommodate and hold said second free end of a corresponding syringe (2, 3) in a movable position along said longitudinal direction (6), such that a distance between said at least two fixing elements (8, 9) is variable; - adjusting the position of the at least one fixing element (9) according to the size of the at least one pair of syringes (2, 3) and / or the amount of fluid loaded into the at least one pair of syringes (2, 3); fastening said at least one pair of syringes (2, 3) to said at least two fastening elements (8, 9); selecting a mixing program for transferring the loaded fluid between the at least one pair of syringes (2, 3) comprising a predefined number of transfers having variable and predetermined speeds; executing said mixing program to continuously move said at least one movable carrier (7) forward and backward within a transport range in which said at least one movable carrier (7) is movable in said longitudinal direction (6) to mix said fluids loaded in said at least one pair of syringes (2, 3); A method comprising:

2. 2. The method of claim 1, wherein the fluid is initially loaded into the at least one pair of syringes (2) at a ratio of less than 100% of the capacity of the at least one pair of syringes (2), and the transfer range is determined according to the ratio of the fluid initially loaded into the at least one pair of syringes (2).

3. 3. The method of claim 1, wherein the fluid to be mixed is obtained from the patient's blood.

4. 4. The method of claim 3, wherein the fluids to be mixed are a protein gel and activated plasma.

5. 5. The method of claim 4, wherein said at least one pair of syringes (3) has a capacity of 3 ml and the final product obtained is a subcutaneously injectable gel.

6. 5. The method of claim 4, wherein said at least one pair of syringes (2) has a capacity of 3 ml and the final product obtained is an intradermally injectable gel.

7. 5. The method of claim 4, wherein said at least one pair of syringes (2) has a capacity of 20 ml and said final product obtained is a topical serum.

8. 8. The method of claim 7, wherein the transfer range is 74 mm.

9. 8. The method of claim 7, wherein the mixing program includes a first cycle (2 transfers) at a rate of 300 pulses / sec, a second cycle (2 transfers) at a rate of 300 pulses / sec, a third cycle (2 transfers) at a rate of 450 pulses / sec, a fourth cycle (2 transfers) at a rate of 600 pulses / sec, a fifth cycle (2 transfers) at a rate of 750 pulses / sec, a sixth cycle (2 transfers) at a rate of 900 pulses / sec, a seventh cycle (2 transfers) at a rate of 1000 pulses / sec, and subsequent cycles.

10. 10. The method of claim 9, wherein a total of 120 transfers are performed.

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