• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    In vivo uterine fluid collection device. A uterine fluid collection device is described that can be used in vivo in both animals and humans without its use causing dilution of the fluid components or damage to the endometrium. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2822399A1
    申请号:ES201930958
    申请日:2019-10-31
    公开日:2021-04-30
    发明作者:Reviriego Rafael Latorre；Gouveia Analuce Canha
    申请人:Universidad de Murcia；
    IPC主号:
    专利说明:

    [0003] TECHNICAL FIELD OF THE INVENTION
    [0005] The present invention relates to a uterine fluid collection device that can be used in vivo in both animals and humans without its use causing dilution of the uterine fluid components or damage to the endometrium.
    [0007] STATE OF THE ART
    [0009] The benefits of supplementing embryo culture media with fluids from the female reproductive tract have promoted the development of strategies for collecting these fluids. Specifically, it has been shown that the composition of in vitro fertilization (IVF) and embryo culture media influences implantation rates, pregnancy and the weight of the offspring at the time of birth.
    [0010] For this reason, an attempt has been made to mimic as much as possible the conditions in which the embryo is in the female reproductive tract. To do this, a possible strategy is to approximate the composition of the chemically defined media to that of the reproductive fluids of the oviduct and uterus.
    [0011] This leads to a growing interest in developing methods for collecting these fluids under minimally invasive conditions, and without causing changes in the qualitative and quantitative composition of the collected fluids.
    [0012] In the case of the human species, the canal of the cervix and the lumen of the uterine cavity are anatomical structures of reduced dimensions, which makes vaginal access difficult. The epithelium that lines these anatomical structures is very delicate and extremely vascular. All of this makes it difficult to collect large enough volumes of fluid to allow its characterization and subsequent use as a supplement to embryo culture media.
    [0013] The most common uterine fluid collection strategy in humans is uterine lavage. This technique has allowed the identification of some proteins that constitute these fluids, but, since it is not possible to extrapolate the dilution factor to which the identified constituents are found, this technique does not allow the quantitative characterization of all the constituents of the uterine fluid. Therefore, the use of uterine lavage prevents an accurate quantification of the constituents of the extracted fluids.
    [0014] In order to avoid the limitations of uterine lavage, different methods of obtaining pure reproductive fluids have been tried, mainly without dilution factors. obtained by aspiration. The most widely used aspiration systems have been through the introduction of different types of embryo transfer cannulas.
    [0015] The use of artificial insemination catheters has also been described since, unlike embryo transfer catheters, they have two lateral orifices, which allows the volume of fluid collected to be increased. In this case, and using a vaginal speculum, the cervix is visualized and the catheter is then inserted until it is well positioned; it is then attached to a syringe to gradually vacuum and aspirate the fluid. However, both embryo transfer cannulas and artificial insemination catheters used primarily in humans employ suction or an automatic vacuum source. They obtain a reduced volume of sample and cause damage to the endometrium that could lead to bleeding, altering the original composition of the collected fluids.
    [0016] On the other hand, in porcine and bovine species an ex vivo technique has been described to obtain purified samples of oviductal and uterine fluid (Patent ES2532658B2). However, ex vivo harvesting makes the activation of signaling pathways inherent in postmortem cellular and biological processes inevitable, or of the coagulation cascade in excised organs.
    [0017] In short, according to the state of the art, it can be pointed out that there are no known devices that allow a reasonable volume of uterine fluid to be collected in vivo , without causing endometrial damage and / or contamination with blood or cervical mucus.
    [0018] Therefore, it is still necessary to develop devices that allow the collection of these fluids under in vivo conditions.
    [0020] BRIEF DESCRIPTION OF THE INVENTION
    [0021] The present invention relates to a device for collecting uterine fluid in vivo by capillary action, wherein said device comprises:
    [0023] - a hollow cylindrical tube (7) comprising in turn:
    [0025] a proximal portion (1), which contains a distal end (1a) and a proximal end (1b), and in which said proximal portion (1) allows the insertion and fixation of a push mechanism (9) of the device within the uterus;
    [0027] an intermediate portion (2), containing a distal end (2a) and a proximal end (2b); Y
    [0029] wherein the proximal end (2b) of the intermediate portion (2) is attached to the distal end (1a) of the proximal portion (1);
    [0030] - a solid cylindrical distal part (3), containing a distal end (3a) and a proximal end (3b), in which the proximal end (3b) of the distal part (3) is attached to the distal end (2a ) of the intermediate portion (2), so as to close the gap of the tube (7) at said distal end (2a);
    [0032] and where said intermediate portion (2) is characterized in that it also comprises at least one slot (6) with a length of at least 2 cm and a width less than or equal to 1 mm, which allow the entry of uterine fluid by capillary action, from the outside to the inside of said intermediate portion (2), said uterine fluid being retained inside the tube (7).
    [0034] BRIEF DESCRIPTION OF THE FIGURES
    [0035] FIG. 1. External appearance of a device according to the present invention.
    [0036] FIG. 2. Sagittal section of a device according to the present invention where the interior can be observed.
    [0037] FIG. 3. Intraluminal view of a device according to the present invention.
    [0038] FIG. 4. External appearance of an embodiment of the sheath (8) open at both ends, which can be used with the device of the present invention. The narrower distal opening is marked with a circle (B '), adopting an acuminate shape that adapts to the distal end (3a) of the distal part (3).
    [0039] FIG. 5 . Figure 5A shows the external appearance of a metal guide that can be used as a push mechanism (9) for the device of the present invention. Figure 5B shows an enlarged detail of the end (B ') intended to be inserted into the proximal portion (1) of the tube (7) of the device of the invention. Figure 5C shows an even more enlarged detail of said end (C '), in which the fixing means (5) used can be seen, by means of a threaded coupling.
    [0040] FIG. 6. Figure 6A shows a sagittal section of a device according to the invention, in which a push mechanism (9) such as that described in figure 5 is fixed. Figure 6B shows an enlarged detail of the part marked as (B ') in figure 6A, showing the detail of the fixing means (5) by means of a threaded coupling of the pushing mechanism. Figure 6C shows the external appearance of the device shown in Figure 6A. FIG. 7 . Figure 7A shows the external appearance of a device according to the invention, to which a push mechanism (9) such as that described in Figure 5 is attached, and inserted in a sheath (8) such as that described in Figure 4. Figure 7B shows the sagittal section of the device of Figure 7A.
    [0041] DETAILED DESCRIPTION
    [0043] The present invention describes a flexible device for the collection of uterine fluid in vivo, the design of which makes it possible to capture uterine fluid by capillary action in an effective and reproducible way and extrapolated for different species of mammals.
    [0045] For the purposes of the present invention, capillarity is defined as the property of liquids to move through the interior of a more or less narrow tube due to the surface tension of said liquid with the interior of said tube.
    [0047] For the purposes of the present invention, the term "comprises" indicates that it includes a group of characteristics, but does not exclude the presence of other characteristics, as long as the presence of the other characteristics does not make the claim impracticable. In addition, the terms "consists de ”," contains "," includes "," has "," encompasses "and synonyms of these terms must be interpreted in the same way as the term" comprises ".
    [0049] Additionally, for the purposes of the present invention, the term "comprises" may be replaced by any of the terms "consists of", "consists of", "consists substantially of" or "consists substantially of". Thus, when the term "comprises" refers to a group of technical characteristics A, B and C, it should be interpreted that it may additionally include other technical characteristics in addition to technical characteristics A, B and C, as long as the presence of the others characteristics does not make the claim impracticable, but it can also be interpreted as comprising only said characteristics A, B and C or, substantially said characteristics A, B and C and, therefore, the term "comprises" refers to a group comprising the characteristics A, B, and C should be construed to include a group consisting of characteristics A, B, and C, or consisting substantially of characteristics A, B, and C.
    [0051] Thus, the present invention refers to a device for collecting uterine fluid in vivo by capillary action, wherein said device comprises:
    [0053] - a hollow cylindrical tube (7) comprising in turn:
    [0055] - a proximal portion (1), which contains a distal end (1a) and a proximal end (1b), and in which said proximal portion (1) allows the insertion and fixation of a push mechanism (9) of the device inside of the uterus;
    [0057] - an intermediate portion (2), containing a distal end (2a) and a proximal end (2b); Y
    [0059] wherein the proximal end (2b) of the intermediate portion (2) is attached to the distal end (1a) of the proximal portion (1);
    [0060] - a solid cylindrical distal part (3), containing a distal end (3a) and a proximal end (3b), in which the proximal end (3b) of the distal part (3) is attached to the distal end (2a ) of the intermediate portion (2), so as to close the gap of the tube (7) at said distal end (2a);
    [0062] and where said intermediate portion (2) is characterized in that it also comprises at least one slot (6) with a length of at least 2 cm and a width less than or equal to 1 mm, which allow the entry of uterine fluid by capillary action, from the outside to the inside of said intermediate portion (2), said uterine fluid being retained inside the tube (7).
    [0063] In one embodiment of the invention the device is characterized by being made of a flexible material. Preferably, the device is made of a biocompatible material, more preferably plastic.
    [0065] The device, therefore, is a catheter that can be made with any biocompatible material in order to be in contact with mucosa, ensuring safe collection, without toxicity effects for the uterine fluid donor.
    [0067] On the other hand, both the tube (7) and the distal part (3) have a cylindrical shape, necessary to be able to adapt to the spherical lumen of the cervical canal.
    [0069] In one embodiment the tube (7) comprises:
    [0071] - a proximal portion (1) of variable length. The purpose of this portion is to adapt a guide or any mechanism (9) that allows the catheter to be pushed into the uterus.
    [0073] Preferably, the proximal portion (1) has a length comprised between 1 and 3 cm.
    [0074] Preferably, the outer diameter of this proximal portion (1) is between 2 and 7mm. Also preferably, the inside diameter of this proximal portion (1) is between 0.5 and 5mm.
    [0076] - an intermediate portion (2) of variable length. This portion allows the device to adapt to the dimensions of the uterus and, moreover, also allows contact of the catheter with the largest possible endometrial surface.
    [0078] Preferably, the intermediate portion (2) has a length between 2 and 12 cm.
    [0080] Preferably, this intermediate portion (2) has a progressive curvature (4), so that the catheter adapts to the curvature that the uterine cavity presents from the body of the uterus towards the uterine tubes or towards the uterine horns. More preferably said curvature (4) is between 10 and 30 degrees. Preferably, the outer diameter of this intermediate portion (2) is comprised between 2 and 7mm and its inner diameter is comprised between 0.5 and 5mm.
    [0082] - Finally, and after the intermediate portion (2), the device has a distal part (3), compact (that is, solid) and closed.
    [0084] Preferably the distal part (3) has a length between 0.2 and 5cm.
    [0085] Also preferably, the external diameter of this distal part (3) is smaller than the rest of the device, to favor entry into the cervix by acting as a guide.
    [0086] Preferably, the distal part (3) has a diameter between 0.5 mm and 4 mm.
    [0087] Furthermore, this distal part (3) is preferably flexible, to adapt to the vaginal and uterine orifices of the cervix, ensuring its passage through the cervix (cervix), without causing any iatrogenic injury.
    [0089] Thus, the size of the device of the invention is variable, including smaller sizes for, for example, humans and larger sizes for, for example, mares and cows.
    [0090] In a preferred embodiment of the device according to the present invention, the proximal portion (1) and the intermediate portion (2) have an external diameter between 2 mm and 7 mm.
    [0092] Preferably the proximal portion (1) and the intermediate portion (2) have an internal diameter comprised between 0.5 mm and 5 mm.
    [0094] In a preferred embodiment of the device according to the present invention, the intermediate portion (2) has a length between 2 cm to 12 cm and a progressive curvature (4) of between 10 to 30 degrees.
    [0096] Preferably, the distal part (3) has a diameter smaller than the external diameter of the proximal portion (1) and that of the intermediate portion (2), to facilitate the passage of the device through the cervical canal.
    [0098] In a preferred embodiment of the device of the present invention, the distal end (3a) of the distal part (3) has a blunt shape. Preferably, the distal end (3a) of the distal part (3) is hemispherical in shape.
    [0100] In this way, the device of the invention has an anatomical design so that its length and diameter adapt to the anatomy of the female reproductive system of any mammal, the cervix and uterine lumen of the species under study, and it has the physical properties necessary to prevent endometrial damage and to maximize fluid collection.
    [0102] So that the device can reach the uterine cavity free of vaginal and cervical secretions, it is covered by a sheath. In this sense, polypropylene sheaths or any biocompatible material can be used, variable in size according to each species.
    [0104] Thus, in one embodiment, the device according to the present invention further comprises a hollow sheath (8) open at least one end, which concentrically surrounds the tube (7) and the distal part (3), so that the device can move freely along the longitudinal axis of the sheath (8). If the sheath is only open at one end, it must be configured so that the distal part (3) can pass through it.
    [0106] In one embodiment of the invention, the sheath (8) is open at its two ends, comprising a distal opening and another proximal opening, where the distal opening progressively narrows, adopting an accumulated shape that adapts to the distal end (3a). of the distal part (3), as shown in figure 7 .
    [0108] In one embodiment of the invention, the push mechanism (9) is fixed to the proximal end (1a) of the proximal portion (1), and is configured to move the entire device of the invention along the sheath ( 8) until reaching its distal opening. In this embodiment of the invention the sheath (8) with the device of the invention is pushed along the vagina and cervix. Once in the uterine cavity, the position of the sheath and the device are fixed along the interior of the sheath to bring the device into contact with the uterine mucosa and allow collection of the uterine fluid by capillary action. In one embodiment of the invention, to remove the device the same sequence of maneuvers is carried out, but in the opposite direction, applying traction instead of pushing force. Thus, in one embodiment of the invention, the device is collected inside the sheath (8), pulling the push system, and then the sheath (8) with the device inside is extracted.
    [0109] The device also has a design that allows it to be collected in several places since the uterine fluid is not located in a specific place, but is distributed evenly over the surface of the endometrium. Therefore, to the extent that the access points to the interior of the device cover a greater surface area, the more options will exist of capturing fluid by capillary action. For this, the device comprises a system of grooves (6), in a variable number, arranged in a spiral, or in any other way, distributed in the intermediate part (2) of the tube (7), allowing the entry of fluid by capillary action from different points of the endometrium, maximizing the efficiency of the collection.
    [0111] Thus, the grooves (6) preferably have a length of at least 2 cm, and a width equal to or less than 1 mm.
    [0113] In a preferred embodiment of the invention, the device comprises at least 3 slots.
    [0114] In a preferred embodiment of the invention the grooves (6) extend from the distal end (2a) to the proximal end (2b) of the intermediate portion (2).
    [0116] In a more preferred embodiment of the invention the grooves (6) extend from the distal end (2a) to the proximal end (2b) of the intermediate portion (2) in a helical manner, or with a helical distribution.
    [0118] Figures 1 and 2 show the aspect and sagittal section of a preferred embodiment of the device of the invention in which the device has an invention, the grooves (6) extend from the distal end (2a) to the proximal end (2b) of the intermediate portion (2) in a helical manner, or with a helical distribution. Figure 3 shows the intraluminal view of this embodiment of the device of the invention.
    [0120] The grooves increase the surface of contact with the endometrium in the three planes of the space, increasing the collection of fluid. In addition, the grooves give the catheter a high degree of flexibility to be able to manipulate it within the sheath and once it is in the uterine cavity. To this must be added that the grooves exert a capillary drag effect on the endometrium, without tearing it, which favors the entry of fluid into the device.
    [0122] In a preferred embodiment of the invention, the width of the grooves (6) is between 100 pm and 700 pm.
    [0124] In an embodiment of the invention, the interior of the proximal portion (1) comprises fixing means (5) of the push mechanism (9) to said proximal portion (1).
    [0126] In one embodiment of the invention, the pushing mechanism consists of a rod of any material, preferably plastic, which is fixed to the device of the invention to allow it to advance inside the sheath (8). In one embodiment of the invention the push mechanism (9) is fixed inside the proximal portion (1) of the device of the invention, and the fixing means (5) is a threaded coupling, quick coupling or even being attached inside said proximal portion (1).
    [0127] The embodiment of the push mechanism (9) shown in Figure 5 is a metal rod that is fixed to the interior of the proximal portion (1) of the tube (7) of an embodiment preferred method of the device of the invention, by means of a threaded coupling. Figure 6 shows a preferred embodiment of the device of the invention, fixed to the metal rod (9) shown in Figure 5. Figure 7 shows the assembly of a preferred embodiment of the device of the invention, fixed to the metal rod (9 ) shown in Figure 5, and enveloped by a sheath embodiment (8) shown in Figure 4.
    [0128] The release of the uterine fluid collected in the device of the invention, once it is extracted, can be carried out in various ways, for example, subjecting it to centrifugation. Unlike other catheters, this one is completely atraumatic when it contacts the endometrial mucosa. Furthermore, the device of the invention collects the fluid by capillary action, so it is not necessary to resort to suction force as is the case with commercial intrauterine catheters for embryo transfer or endometrial biopsy or cervical mucus.
    [0129] Furthermore, the in vivo uterine fluid collection device of the invention allows pure fluid to be collected without dilution factors inherent to traditional uterine lavage collections. On the other hand, the design with a multipoint collection system, thanks to the grooves (6), allows collecting a sufficient volume to carry out the quality controls, necessary for storage in the sanitary conditions required for use as a supplement to the embryo culture media or for precision research work requiring absolute quantitative characterization.
    [0130] Finally, the use of the device of the invention allows the collection of uterine fluid that does not present cellular debris, cervical mucus, or blood debris, since the use of the device of the invention does not produce bleeding in contact with the endometrium.
    [0132] EXAMPLES
    [0134] Comparative example 1: Evaluation of state-of-the-art devices
    [0136] Various devices already on the market with potential for the collection of uterine fluid have been evaluated. These devices were first tested in ex vivo ovine uteri from the slaughterhouse. In addition, an in vivo experimental phase was carried out using endoscopic techniques to evaluate, with direct vision, the passage of the devices through the cervical canal and uterine cavity. In the human species, different catheters have been tested in vivo in oocyte donors from fertility clinics and in ex vivo conditions with the uteruses of women undergoing hysterectomies. Specifically, these are the devices studied and the results obtained:
    [0137] A. HydraFlock® (Medical wire): Designed for higher absorbency compared to standard swabs. HydraFlock® fibers have a microstructure that allows rapid absorption and maximum release of biological samples. It is not traumatic for the mucosa, it absorbs some fluid, but its main limitations are that it does not allow the subsequent release of the collected fluid, it remains between its fibers and centrifugation is not effective.
    [0139] B. Embryo transfer catheters from different commercial companies:
    [0140] Trials have been conducted with the following devices:
    [0141] - Embryo Transfer Catheter Set from Labotect Labor-Technik-Gottingen GMBH:
    [0142] - Kitazato® ET catheter
    [0143] - Emtrac Delphin (Gynetics®)
    [0144] - Wallace® Classic (Coopersurgical®)
    [0145] Aspiration with these embryo transfer catheters was performed by coupling syringes of different caliber (1ml, 2ml, 5ml and 10ml) and the Aspirator 3 automatic aspiration system.
    [0146] In all cases, it is possible to collect uterine fluid both ex vivo and in vivo, but only occasionally and in very small quantities (0.7 µl). The aspiration point is very small and therefore of limited effectiveness, and can cause bleeding in the aspiration area.
    [0148] C. Insemination devices: Tests have been carried out with artificial insemination catheters (Standard Model 120400S from CDD laboratoires) that have two lateral orifices. Aspiration with these embryo transfer catheters is also performed by coupling syringes of different caliber (1ml, 2ml, 5ml and 10ml).
    [0149] With these devices it is possible to collect uterine fluid both ex vivo and in vivo, but only occasionally and in very small quantities, since no volume of fluid was collected in the two experiments carried out. The aspiration point is very small and therefore of limited effectiveness, and can cause bleeding in the aspiration area.
    [0151] D. Pipelle de Cornier. Endometrial mucosa suction curette (Laboratoire CCD):
    [0152] This device is a flexible and transparent polypropylene 3.10 mm external diameter, 2.6 mm internal diameter and 23.5 cm long, with a 2.1 mm diameter side hole at the distal end and four markings 4, 7, 8 and 10 cm from the distal end. It has an internal plunger to cause aspiration of the endometrium.
    [0153] It allows the collection of uterine fluid (a mean value of 12.8 ± 22.5 ql of uterine fluid was collected, n = 15), although being designed to remove the endometrium it caused bleeding (a mean value of 0.31 ± 0.15 g was collected / dL of hemoglobin).
    [0155] E. Mucat® (CCD Laboratory): Device indicated for direct exocervical or endocervical aspiration and the Hühner test. It is less aggressive to the endometrium than Pipelle de Cornier because it has a smooth opening at the distal tip. Aspiration, as with Pipelle de Cornier, is also done with the integrated plunger, without a syringe. It allows fluid to be collected (21.4 ± 19.1 ql were collected as a mean value, n = 32) although it causes a considerable amount of blood (0.12 g / dl of hemoglobin was collected as a mean value), it also drags tissue and mucus.
    [0157] Example 2: Device of the invention for collection of uterine fluid in humans
    [0158] The device was made of transparent MED610 biocompatible material (Stratasys Headquarters). The proximal portion (1) of the fabricated device was 1 cm long, 2.5 mm outside diameter, and 1.5 mm inside diameter. The intermediate portion (2) of the manufactured device has a length of 4 cm, an outer diameter of 2.5 mm and an inner diameter of 1.5 mm. The intermediate portion (2) of the manufactured device had a curvature angle (4) of 30 ° and is traversed by 4 slots (6) extending from the distal end (2a) to the proximal end (2b) of the intermediate portion (2 ) with a slot width of 500 qm, through which uterine fluid penetrates and is trapped by capillary action. The interior of the manufactured proximal portion (1) included a thread system allowing a guide (eg metal) to be coupled to push the device into the uterus. The distal part (3) of the manufactured device is 1 cm long and has a diameter of 1.5 mm.
    [0160] Uterine fluid collection procedure.
    [0161] The device was sterilized according to the maximum temperature it can withstand, that is, by gas plasma at temperatures below 45-50 ° C. For the collection of uterine fluid in humans, the following steps were carried out:
    [0162] to. Position the patient in the lithotomy position. Insert the vaginal speculum to expose the cervix. The condition of the cervix and endometrium is checked, and the length and angle of curvature of the device, and the guide, is decided before use.
    [0163] b. Screw the metal guide (push mechanism (9)) into the device and place it inside the sheath (8). In this case a sheath has been used (8) introductory with a smooth surface to reduce friction to the maximum ( Radifocus® Introducer II Temuro interventional systems) designed for vascular access and a metallic guide manufactured by the Technical Unit of the University of Murcia has been used that includes a metallic plunger that acts as a push mechanism (9) (see figure 6).
    [0164] c. Wash the vulva and vagina with sterile saline.
    [0165] d. Insert the device, covered by the sheath, into the cervix.
    [0166] and. Check that the device reaches the uterus with ultrasound control. The metal plunger of the metal guide is depressed to push the device deep into the uterus.
    [0167] F. Make light movements for 5 to 10 min to stimulate the entry of the fluid by capillary action through the grooves.
    [0168] g. Insert the device back into the sheath, pulled by the push system.
    [0169] h. The device is removed, the vaginal speculum is removed, and the patient is kept at rest.
    [0170] i. The device is transferred to a 10ml tube.
    [0171] j. Centrifuge at 1200g for 5min.
    [0172] k. The device is removed. The fluid is aliquoted and stored at -80 ° C.
    [0176] Fable 1
    [0178] Example 3: Device of the invention for collecting uterine fluid in bovine species.
    [0179] The device was made of transparent MED610 biocompatible material. The proximal portion (1) has a length of 2 cm, an outer diameter of 5 mm and an inner diameter of 3 mm. The intermediate portion (2) has a length of 8 cm, an outer diameter of 5 mm and an inner diameter of 3 mm. This intermediate portion (2) was designed with a 10 ° angle of curvature (4) and 4 grooves (6), which extend from the distal end (2a) to the proximal end (2b) of said intermediate portion (2) and have a width of 500 pm wide, through which the uterine fluid penetrates and is trapped by capillary action The interior of the proximal portion (1) forms a thread system that allows a guide (9) to be attached, eg metal, to push the device into the uterus. For its part, the distal part (3) of the device is 3 cm long and has a diameter of 3 mm.
    [0181] Uterine fluid collection procedure.
    [0182] For the use of the device, it is first sterilized according to the maximum temperature that it supports, that is, by plasma gas at temperatures below 45-50 ° C. The steps to follow for the use of the device in bovine species are the following:
    [0183] A. The cow is placed on a support foal and rectal palpation is performed to locate the ovary with the corpus luteum.
    [0184] B. Low epidural anesthesia (2% xylocaine) is performed.
    [0185] C. The perineal region and vulva are washed with disinfectant soap and water and the region is dried. D. Screw the metal guide (push mechanism (9)) into the device and place it inside the sheath (8). In this case, a probe designed for insemination of mares has been used as sheath (8) (Equine deep AI pipette REF. 17209/1175 MINITUBE), with a smooth round tip for a soft and flexible introduction to facilitate handling. And a metallic guide manufactured by the Technical Unit of the University of Murcia has been used, which comprises a metallic plunger that acts as a push mechanism (9) (see figure 6).
    [0186] E. Before inserting the device, a sterile lubricant is placed in the vagina to make it easier to pass through the cervix.
    [0187] F. With the left hand, the cervix is grasped through the wall of the rectum.
    [0188] G. The device is inserted into the cervical canal with the right hand.
    [0189] H. It is checked that the device reaches the uterus with ultrasound control.
    [0190] I. The metal plunger is depressed to push the device into the uterine cavity. J. Wait 5 to 10 min, moving slightly to stimulate the entry of the fluid by capillary action through the slots.
    [0191] K. The device is re-protected within the sheath.
    [0192] L. The device is gently removed and the hand is removed from the rectum.
    [0193] M. The device is transferred to a 10ml tube.
    [0194] N. Centrifuge at 1200 g for 5 min.
    [0195] O. The catheter is removed. The fluid is aliquoted and stored at -80 ° C.,
    [0197] Table 2
    [0199] The collected uterine fluid does not contain dilution factors inherent to traditional uterine lavage collected. In addition, the volume collected is sufficient to carry out quality controls, which require at least 2-5 pl of fluid, necessary for storage under the sanitary conditions required for its use as a supplement to embryo culture media or for precision research work that requires absolute quantitative characterization.
    [0200] The fluid collected from both human donors and cows in the study did not present cellular debris or cervical mucus. The color of the collected fluid is translucent yellow, which shows the absence of bleeding due to contact with the endometrium, by this collection method.
    权利要求:
    Claims (19)
    [1]
    1. Device for collecting uterine fluid in vivo by capillary action, wherein said device comprises:
    - a hollow cylindrical tube (7) comprising in turn:
    a proximal portion (1), which contains a distal end (1a) and a proximal end (1b), and in which said proximal portion (1) allows the insertion and fixation of a push mechanism (9) of the device within the uterus;
    an intermediate portion (2), containing a distal end (2a) and a proximal end (2b);
    and wherein the proximal end (2b) of the intermediate portion (2) is attached to the distal end (1a) of the proximal portion (1);
    - a solid cylindrical distal part (3), containing a distal end (3a) and a proximal end (3b), in which the proximal end (3b) of the distal part (3) is attached to the distal end (2a ) of the intermediate portion (2), so as to close the gap of the tube (7) at said distal end (2a);
    and where said intermediate portion (2) is characterized in that it also comprises at least one slot (6) with a length of at least 2 cm and a width less than or equal to 1 mm, which allow entry of uterine fluid by capillary action, of the exterior to the interior of said intermediate portion (2), said uterine fluid being retained inside the tube (7).
    [2]
    Device according to claim 1 in which the width of the grooves (6) is between 100 pm and 700 pm.
    [3]
    Device according to either of claims 1 or 2, in which the grooves (6) extend from the distal end (2a) to the proximal end (2b) of the intermediate portion (2).
    [4]
    Device according to any one of claims 1 to 3, in which the grooves (6) extend from the distal end (2a) to the proximal end (2b) of the intermediate portion (2) in a helical manner or distribution. .
    [5]
    Device according to any one of claims 1 to 4, in which the intermediate portion (2) comprises at least three grooves (6).
    [6]
    Device according to any one of claims 1 to 5, in which the interior of the proximal portion (1) comprises a means for fixing (5) the push mechanism (9) to said proximal portion (1).
    [7]
    Device according to claim 6, in which the fixing means (5) is a threaded coupling.
    [8]
    Device according to any one of claims 1 to 7, in which the proximal portion (1) and the intermediate portion (2) have an external diameter comprised between 2 mm and 7 mm.
    [9]
    Device according to any of claims 1 to 8, in which the proximal portion (1) and the intermediate portion (2) have an internal diameter comprised between 0.5 mm and 5 mm.
    [10]
    Device according to any one of claims 1 to 9, in which the proximal portion (1) has a length of between 1 cm and 3 cm.
    [11]
    Device according to any one of claims 1 to 10, in which the intermediate portion (2) has a length of 2 cm to 12 cm in length and a progressive curvature (4) of between 10 to 30 degrees.
    [12]
    Device according to any of claims 1 to 11, wherein the distal part (3) has a diameter smaller than the external diameter of the proximal portion (1) and the intermediate portion (2), to facilitate passage of the device through the cervical canal.
    [13]
    Device according to any one of claims 1 to 12, wherein the distal end (3a) of the distal part (3) is blunt-shaped.
    [14]
    Device according to any one of claims 1 to 13, in which the distal end (3a) of the distal part (3) has a hemispherical shape.
    [15]
    Device according to any one of claims 1 to 14, in which the distal part (3) has a diameter comprised between 0.5 mm and 4 mm.
    [16]
    Device according to any one of claims 1 to 15, in which the distal part (3) has a length of 0.2 cm to 5 cm.
    [17]
    17. Device according to any of claims 1 to 16, characterized in that it is made of a flexible material.
    [18]
    18. Device according to any of claims 1 to 17, characterized in that it is made of a biocompatible material.
    [19]
    Device according to any one of claims 1 to 18, further comprising a sheath (8) hollow and open at at least one end, which concentrically surrounds the tube (7) and the distal part (3), so that the device can move freely along the longitudinal axis of the sheath (8).
    类似技术:
    公开号 | 公开日 | 专利标题
    ES2702367T3|2019-02-28|Sampling needle
    EP1177776B1|2004-05-06|Device and method for introducing and/or collecting fluids from the interior of the uterus of an animal
    ES2247318T3|2006-03-01|INTRA-UTERINE INSEMINATION DEVICE FOR PIGS AND EMBRYO TRANSPLANT.
    Drost et al.1976|A device for nonsurgical recovery of bovine embryos
    US5147335A|1992-09-15|Transurethrovesical biopsy, amniocentesis and biological sampling guide
    ES2822399B2|2022-02-16|IN VIVO UTERINE FLUID COLLECTION DEVICE
    US20100268023A1|2010-10-21|Medical Instrument, In Particular Hysteroscope
    Lévy2016|Videovaginoscopy of the canine vagina
    Payan-Carreira et al.2011|Artificial insemination in dogs
    US10779859B2|2020-09-22|Arrangement for the ultrasound-assisted manipulation on the female reproductive organs of large mammals and use of the arrangement
    RU2608718C2|2017-01-23|Method of bladder catheterization in fishes
    RU66201U1|2007-09-10|DEVICE FOR TAKING SAMPLES OF THE CONTAINED CAVITY OF THE UTERINE OF HOME CARNIVORES AND INTRAUSAL INTRODUCTION OF LIQUID MEDICINES
    KR970007677B1|1997-05-15|Artificial insemination and embryo transfer device
    KR20170033950A|2017-03-28|Gathering eggs for livestock and animals
    Dascanio et al.2021|Breeding with Fresh or Cooled Semen
    RU175731U1|2017-12-15|MEDICAL CATHETER
    BR102016024226A2|2018-05-02|VETERINARY MEDICAL URETRAL PROBE PASSAGE DEVICE
    McCarthy1996|Cystoscopy and biopsy of the feline lower urinary tract
    SU725665A1|1980-04-05|Apparatus for implantating zygotes to animals
    CN210749320U|2020-06-16|External member is put into to urethra locator under endoscope
    Moore et al.2008|Rigid endoscopy: urethrocystoscopy and vaginoscopy
    KR200442497Y1|2008-11-14|A vaginal speculum insertion in bladder catheter
    RU2249442C2|2005-04-10|Device for treating subclinical form of endometritis in cattle
    Maenhoudt et al.2021|Vaginal Endoscopy in the Bitch
    KR20190104148A|2019-09-06|Brush Biopsy Devices, Kits, and Methods
    同族专利:
    公开号 | 公开日
    ES2822399B2|2022-02-16|
    WO2021084153A1|2021-05-06|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    IL63793A|1980-12-22|1986-10-31|Richard G Seed|Uterine catheter for artificial embryonation and tissue recovery|
    EP0262966A2|1986-10-01|1988-04-06|Animal House, Inc.|Sampling device|
    ES2156579A1|2000-01-20|2001-06-16|Univ Murcia|Device and method for introducing and/or collecting fluids from the interior of the uterus of an animal|
    ES2348528A1|2008-09-26|2010-12-09|Universidad De Murcia|Device and method for inserting or obtaining a fluid with gametes, embryos or any other type of solution in the oviduct of a sow|
    法律状态:
    2021-04-30| BA2A| Patent application published|Ref document number: 2822399 Country of ref document: ES Kind code of ref document: A1 Effective date: 20210430 |
    2022-02-16| FG2A| Definitive protection|Ref document number: 2822399 Country of ref document: ES Kind code of ref document: B2 Effective date: 20220216 |
    优先权:
    申请号 | 申请日 | 专利标题
    ES201930958A|ES2822399B2|2019-10-31|2019-10-31|IN VIVO UTERINE FLUID COLLECTION DEVICE|ES201930958A| ES2822399B2|2019-10-31|2019-10-31|IN VIVO UTERINE FLUID COLLECTION DEVICE|
    PCT/ES2020/070666| WO2021084153A1|2019-10-31|2020-10-30|Device for collecting uterine fluid in vivo|
    [返回顶部]