CN108852569B - Degradable supporting diaphragm device for preventing and treating intrauterine adhesion - Google Patents
Degradable supporting diaphragm device for preventing and treating intrauterine adhesion Download PDFInfo
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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Abstract
The invention discloses a degradable supporting diaphragm device for preventing and treating intrauterine adhesion, which comprises a bioabsorbable supporting device and a matched conveyor; the bio-absorbable support device comprises a biological membrane, a nickel-titanium alloy wire framework and a drug coating; the shape of the biological membrane is matched with the uterine cavity; the nickel-titanium alloy wire framework comprises an embedded section and an extension section; the drug coating is loaded on the outer surface and/or the inner surface of the biological membrane; the conveyor comprises a pushing rod and a conveying sleeve, the conveying sleeve can be sleeved outside the pushing rod in a matching mode, the front end of the pushing rod is provided with a bioabsorbable supporting device, the rear end of the pushing rod is provided with finger buckles, and the outer wall of the conveying sleeve is provided with two finger buckles. The device does not need to be taken out after being implanted, reduces the uncomfortable feeling of the uterus of a patient during the retention period, is completely absorbed by the human body after being degraded, does not leave a lead, and does not have the infection risk of invading germs through the vagina; is particularly suitable for re-adhesion after the intrauterine adhesion separation.
Description
Technical Field
The invention relates to the technical field of medical instruments, in particular to a degradable supporting diaphragm device for preventing and treating intrauterine adhesion.
Background
The uterus is an organ of a female which generates menstruation and breeds a fetus, is positioned in the center of a pelvic cavity, and is a unique visceral organ of the female. The uterus size is related to age and fertility, and the uterus of adult female is about 7.5cm long, 5cm wide and 3cm thick, and can be divided into three parts, namely, the bottom, body and neck. The uterine cavity is in an inverted triangle shape, the depth is about 6cm, and two upper corners are uterine horns and lead to the oviduct. The lower end is narrow and is an isthmus part, and the length is about 1 cm.
From the anatomical structure of the uterus, the main components are the muscles, the anterior and posterior walls of the body of the uterus are almost in contact with each other, and the middle uterine cavity is only a fissure. The wall of the uterus consists of three layers of tissues, namely a serosal layer, a muscular layer and a mucous layer; the mucosa layer is an endometrium layer and can be divided into three layers, namely a compact layer, a sponge layer and a basal layer. The stratum compactum and the stratum spongium are proliferative zones regenerated from the basal layer, collectively called the functional layer, sensitive to sex hormones, subject to cyclic changes under the influence of ovarian hormones, and if not pregnant, the functional layer falls off at the end of each cycle with uterine bleeding, clinically manifested as menstruation. The basal layer is close to the muscle layer and is insensitive to ovarian hormone without periodic changes. Normal endometrial glands can secrete a thin alkaline fluid to keep the uterine cavity moist. Thus, the anterior and posterior walls of the normal uterus, although closely spaced, do not adhere and grow together.
From the practical clinical point of view, women can cause various pathological changes in the uterine region due to uterine cavity operations such as abortion, intrauterine device placement and removal, operation and the like, infection and the like, uterine diseases are one of the most common diseases of women, and the normal life and health of patients are seriously influenced, so that the ability of inoculating new lives is influenced. These pathologies include endometritis, endometriosis, uterine hypertrophy, uterine polyps, uterine fibroids, uterine cysts, uterine prolapse, endometrial cancer, and the like.
At present, the treatment aiming at the pathological changes comprises means such as drug treatment, minimally invasive surgery treatment and the like. The effect of drug therapy on the above pathological changes is limited, with the rapid development of minimally invasive technology in the field of surgery, hysteroscopy and surgery are widely popularized in the field of gynecological diagnosis and treatment, and the hysteroscopy has a series of advantages of small wound, less bleeding during surgery and the like, and the operation of using the hysteroscope is called as an important component of minimally invasive surgery. However, most of the operations cause damage to the uterine cavity, and a series of operations such as polyps, myomas, cysts, adhesion excision, uterine curettage and the like can cause damage to the basement layer of the endometrium, particularly damage to the front wall and the rear wall at the same position at the same time, and the uterine cavity is adhered.
From the analysis of the occurrence conditions of intrauterine adhesion, it is currently agreed that, first, trauma to the pregnant uterus is the main cause of intrauterine adhesion. The trauma often occurs after delivery or 1-4 weeks after abortion, and the patient needs to be curetted due to excessive bleeding. During this susceptible period, any trauma can cause the basal layer of the endometrium to fall off, causing the walls of the uterus to adhere to each other, forming permanent adhesions, resulting in the disappearance of the deformation and symmetry of the uterus. Second, trauma to non-pregnant endometrium can also cause intrauterine adhesions. Third, the literature reports that intrauterine adhesions can occur after diagnostic uterine curettage, laparotoma removal, cervical biopsy, endometrial polyp retrieval, intrauterine contraceptive devices, or application of radiation therapy. In addition, intrauterine adhesions may also occur after various hysteroscopic procedures, such as hysteromyomectomy, mediastinectomy, etc.
Therefore, after diagnosis and treatment of uterine diseases are carried out through minimally invasive surgery, the actual clinical problem of uterine adhesion prevention is particularly important to solve because uterine cavities are damaged, the probability that the uterine cavities are adhered together after being attached to a wound surface is high, menstrual blood cannot be smoothly discharged after the uterine cavities are adhered, and women of childbearing age cannot normally conceive. The traditional treatment means for solving the uterine adhesion is separation by operation, and is still easy to relapse after uterine cavity separation operation, and is difficult to radically treat. And the pregnancy after the intrauterine adhesion is high-risk pregnancy with high abortion risk and placenta abnormality, and needs to be closely monitored to prevent and treat complications. Therefore, the treatment of the intrauterine adhesion not only comprises the restoration of the normal shape of the uterine cavity through the hysteroscope operation, but also adopts measures to promote the repair of endometrium, prevent the recurrence of the intrauterine adhesion and finally restore the normal life and the fertility of the patient.
There are many methods and means for preventing re-adhesion after the separation of intrauterine adhesion, but a method capable of absolutely and effectively completely avoiding re-adhesion is still lacked so far, and a uniform treatment standard is also lacked. The main treatments disclosed in the present publication are drug therapy, intrauterine barrier media, balloon dilatation, amnion transplantation, fibro-hysteroscopic exploration and blunt dissection.
The medicament used in the medicament therapy is mainly estrogen, and the measures of conventionally applying the estrogen to the intrauterine adhesion separation operation for sequentially performing an artificial period of 2-3 months or independently applying the estrogen have definite effect on preventing re-adhesion formation after the adhesion separation operation of the patients with light-moderate intrauterine adhesion, and the menstruation recovery and the reproduction prognosis are obviously improved. However, the effect of patients with severe intrauterine adhesion is not optimistic, and the postoperative re-adhesion rate can reach more than 50 percent, which is probably related to serious damage of the intimal basal layer of patients with severe intrauterine adhesion and lack of response to estrogen. Therefore, the role of estrogen in the formation of re-adhesions after adhesion detachment in patients with severe intrauterine adhesions remains to be discussed further.
The intrauterine barrier medium therapy is to insert the spacer into uterus and separate wound with the spacer, so that the wall of uterus cannot be easily attached together. The intrauterine device is clinically used at present, and most scholars place intrauterine devices in uterine cavities after the intrauterine adhesion separation for 2-3 months as a classic method for preventing postoperative re-adhesion. However, the effect of preventing the postoperative re-adhesion of patients with severe intrauterine adhesion is not good enough, the postoperative menstruation recovery and the reproductive prognosis are not obviously improved, and the damage to the endometrial basement layer of the patients is serious and almost no normal intima residue is related. Researchers think that the current clinical copper-containing intrauterine device has limited area, can not effectively separate the front wall and the rear wall of the uterus, can cause excessive inflammatory reaction, leads to release of a large amount of inflammatory mediators and cell factors for promoting adhesion formation, and accelerates the formation of postoperative re-adhesion, so the intrauterine device is not ideal as a barrier medium therapy, cannot completely cover the wound surface of the uterine cavity, and has poor treatment effect.
The balloon dilatation method uses a balloon ureter as a balloon body. Clinical data show that the recovery rate of the intrauterine device of a patient with light-medium intrauterine adhesion is as high as 80%, even more than 90%, the pregnancy rate in the full term reaches 40% -50%, the effect is better than that of an intrauterine device, and the potential problem of secondary damage to the intima can be caused when the intrauterine device is taken out after the intrauterine device is placed in the uterine cavity for 2-3 months, wherein the patient with light-medium intrauterine adhesion keeps a Foley balloon urinary catheter in the uterine cavity for 7-14 days after the adhesion separation. The inverted pear-shaped uterine saccule support released by COOK company is a special-shaped saccule made of a silicone material and can be more suitable for the physiological characteristics of women. The saccule (stent) is used as a stent to ensure that endometrium is proliferated and repaired along the surface of the saccule; the open channel in the catheter can fully drain the uterine inflammatory exudates, and is beneficial to repairing endometrium. However, the balloon (stent) has the defects that hospitalization is required during treatment, secondary infection and even cervical insufficiency are possible, and patients have obvious uterine discomfort; while intrauterine balloon compression is used, it is practically difficult (excessive force) to try again to promote endometrial growth; the method has short treatment period and long-term curative effect of preventing re-adhesion.
The amnion transplantation therapy is characterized in that the amnion is the innermost layer of a placenta, is similar to a conjunctiva tissue structure of human eyes, is smooth, has no blood vessels, nerves and lymph, has certain elasticity and thickness of about 0.02-0.5mm, and is divided into five layers under an electron microscope: the amniotic membrane basement membrane and the amniotic membrane matrix layer contain a large number of different collagen elements, mainly including collagen types i, iii, iv, v and vii, fibronectin, laminin and other components, and the components enable the amniotic membrane to serve as a 'transplanted basement membrane' to play a new healthy and proper matrix role to promote epithelialization. The mechanism of action of the amnion for preventing the re-adhesion of the uterine cavity is not clear, and the main possibility is as follows (1) anti-infection action: the amnion can cling to the surface of the wound by virtue of cellulose per se, so that dead spaces between the wound and the amnion are reduced, and bacterial proliferation and diffusion are inhibited; the cellulose bracket also helps the migration of macrophages, so that the macrophages can smoothly reach the bacterial reproduction part to play a role in sterilization; the amnion can also secrete antibiotics through autocrine action to prevent postoperative infection; (2) biological effects: the amnion has the function of lowering, regulating and promoting the level of TGF-beta 1 which is the most main factor for promoting the growth of the fiber, thereby avoiding the occurrence of re-adhesion and intimal fibrosis; (3) as the "intimal-basal layer of the graft," the amniotic membrane provides a reliable environment for neoepithelial regeneration, increases cell engraftment and epithelial adhesion, and reduces epithelial apoptosis. The surface of the amniotic epithelial cell membrane does not express human histocompatibility complex (HLA) including HLA-A, B, C or DR, beta 2-m and the like, so that the rejection reaction of allograft does not exist, and systemic immunosuppressive treatment is not required. In 2006, Amer et al tried to perform intrauterine amniotic membrane transplantation in 25 middle-severe intrauterine adhesion patients after TCRA surgery by means of the supporting effect of Foley balloon ureters, tried to replace the endometrial basal layer by the regeneration of amniotic epithelium, prevented the re-adhesion formation after TCRA surgery, and promoted the recovery of menstruation and fertility functions. The results of two-time uterine cavity exploration in 4 months after operation show that 12 moderate patients with uterine cavity adhesion do not form re-adhesion, 1 of 13 severe patients with uterine cavity adhesion does not form re-adhesion, and 12 patients have re-adhesion in different degrees: however, the re-adhesion was only mild in 83.33% (10/12) patients and moderate in only 16.67% (2/12) patients with severe tuberculous intrauterine adhesion. It can be seen that, although the recovery effect of the amnion transplantation after the operation of the patient with moderate-severe intrauterine adhesion is better than that of other therapies, the adhesion regeneration is not completely avoided.
The fibro-hysteroscopic exploration and blunt dissection are newly developed treatment methods, namely, the regular uterine cavity exploration is carried out after the uterine cavity adhesion dissection, the newborn loose slight adhesion is treated early, the postoperative intrauterine recovery condition is monitored, the reaction is made in time, and the reformation of compact adhesion and new intimal injury caused by the reformation are avoided. The effect of the treatment method is not very clear, a large amount of clinical research and report data are not available, and in terms of operability, doctors and patients need to frequently perform exploration and blunt separation, and when the newly-born loose slight adhesion is separated in each exploration, new wounds are caused with a high probability, so that the healing time of the patients is delayed, and the probability of infectious diseases is increased.
For example, chinese patent application CN201110058056.9 discloses a drug-carrying membrane stent for preventing and treating intrauterine adhesion, which is composed of a nickel-titanium alloy wire woven and sustained-release drug-carrying membrane with shape memory characteristics, and can damage tissues and cause infection risk when taken out. Chinese patent application CN201210049248.8 discloses a uterine cavity adhesion prevention and treatment device, which comprises a uterine shaped ring and a thin film, wherein the thin film directly adheres to tissues to block the growth of the inner film, so that the risk of infection is high. Chinese patent application CN201210150391.6 discloses a carrier barrier system for preventing and treating intrauterine adhesion, comprising a balloon and an injection carrier, which is also attached to hinder the growth of the intima, and has infection risk. Chinese patent application CN201410540232.6 discloses a uterine cavity adhesion blocking device, which comprises a V-shaped framework adapted to the shape of the uterine cavity, a base rod and a degradable mesh sheet, and is required to be taken out, thereby having infection risk. Meanwhile, a braided stent designed to be a degradable material is also provided, but the degradation time is long (the shortest time is more than 6 months), so that a patient has obvious discomfort and the life of the patient is inconvenient.
Obviously, the anti-adhesion devices in the prior art need to be taken out after being implanted for a period of time, and the tissues are torn again after being taken out again, so that the weak intima tissues are fatally damaged; in addition, in order to be taken out conveniently, the taking-out instrument is generally provided with a lead for taking out, and the lead can always pass through the cervical canal and extend and stay in the vagina in the implantation time period, so that a channel which can reach the interior of the uterus is created for bacteria and the like, and the probability of infection diseases of patients is greatly increased.
Disclosure of Invention
The invention aims to solve the technical problem of providing a degradable supporting diaphragm device for preventing and treating intrauterine adhesion; the device enables the biological diaphragm to enter the uterine cavity very smoothly, reduces the uncomfortable feeling of a patient to the maximum extent, and can be completely stretched after entering the uterine cavity, so that the front wall and the rear wall of the uterine cavity are fully isolated, the damaged endometrium can be quickly recovered by carrying a medicament, various intrauterine adhesions caused by wound after the intrauterine operation can be treated, and the device is particularly suitable for preventing secondary adhesions after the intrauterine adhesion separation.
In order to solve the technical problems, the invention adopts the following technical scheme:
a degradable supporting diaphragm device for preventing and treating intrauterine adhesion comprises a bioabsorbable supporting device and a matched conveyor;
the bio-absorbable support device comprises a biological membrane, a nickel-titanium alloy wire framework and a drug coating; the shape of the biological membrane is matched with the uterine cavity; the nickel-titanium alloy wire framework comprises an embedded section and an extension section, and the embedded section is embedded into the biological membrane and is used for supporting the biological membrane to be in an unfolded state; the drug coating is loaded on the outer surface and/or the inner surface of the biological membrane and is used for promoting the repair of endometrium and preventing adhesion;
the conveyor comprises a pushing rod and a conveying sleeve, the conveying sleeve can be sleeved outside the pushing rod in a matching mode, the front end of the pushing rod is provided with a bioabsorbable supporting device, the rear end of the pushing rod is provided with finger buckles, and the outer wall of the conveying sleeve is provided with two finger buckles.
As a further improvement of the technical scheme, the biomembrane is made of one or more of hyaluronic acid, collagen and polylactic acid.
Preferably, before implantation, the biological membrane is bound at the front end of the pushing rod in the conveying sleeve, and the biological membrane is in a winding tubular shape and has the diameter less than or equal to 0.8 mm.
Preferably, in an unfolded state after implantation, the biological membrane is in an inverted triangle, and the side length of the triangle is 20mm-70 mm; the three corners are replaced by arc corners, and the diameter of the arc is 5mm-20 mm; the thickness of the membrane is 1mm-5 mm.
Preferably, the width of the top of the biofilm sheet in the post-implantation unfolded state is 20-70mm, preferably 40-50 mm; the width of the bottom is 5-20mm, preferably 10-15 mm; the distance between the top and the bottom is 10-50mm, preferably 20-40 mm.
As a further improvement of the technical scheme, the embedded section of the nickel-titanium alloy wire framework is embedded into the outer edge of the biological membrane and surrounds a circle, and the distance from the membrane to the boundary is 3-5 mm.
As a further improvement of the technical scheme, the embedded sections of the nickel-titanium alloy wire framework are dispersed into 3-8 pieces and embedded into the biological membrane.
Preferably, the nitinol wire skeleton has a diameter of 0.35mm to 0.89 mm.
As a further improvement of the technical scheme, the medicine coating consists of soybean lecithin and effective medicines; the effective drug comprises one or two of PDGF (platelet derived growth factor) and GM-CSF (granulocyte-macrophage colony stimulating factor); the soybean lecithin: the mass ratio of the medicine is 1: 1.4-1.6.
Preferably, the PDGF to GM-CSF weight ratio is 10-30: 70-90.
Preferably, the drug loading of the effective drug is between 50 and 100 μ g.
Preferably, the drug coating is between 5-30 μm thick.
As a further improvement of the technical scheme, the length scales are arranged on the outer wall of the conveying sleeve of the conveyor, so that the position of the conveyor entering the uterus can be conveniently measured, and the position of the biological membrane implanted into the uterine cavity is more accurate.
Preferably, the conveyor material comprises one of 304 stainless steel, 316 stainless steel, Polycarbonate (PC), Acrylonitrile Butadiene Styrene (ABS); the outer diameter of the conveyor is 1.0cm-1.5 cm.
The starting materials of the present invention are commercially available, unless otherwise specified, and the equipment used in the present invention may be any equipment conventionally used in the art or may be any equipment known in the art.
Compared with the prior art, the invention has the following beneficial effects:
the degradable supporting diaphragm device for preventing and treating intrauterine adhesion can treat intrauterine adhesion caused by wound after various intrauterine operations, and is particularly suitable for re-adhesion after intrauterine adhesion separation. After hysteroscopic adhesion incision, the instrument is delivered into uterus, and the wound surface is separated by the instrument, so that the uterine wall cannot be easily attached together, and particularly, the repair of the endometrium can be completed through drug treatment. The biological membrane of the invention is formed by completely absorbable biological materials, has biodegradable characteristics, is convenient for implantation operation, does not need to be taken out by operation after implantation, reduces discomfort of the uterus of a patient to the maximum extent during the retention period, is completely absorbed by a human body after degradation, does not leave a lead (tail fiber), and has no infection risk of invading germs through the vagina.
Drawings
The following detailed description of embodiments of the invention is provided in connection with the accompanying drawings
FIG. 1 is a schematic view of a bioabsorbable support device of example 1 of the invention in an unconstrained state prior to implantation;
FIG. 2 is a schematic view of a bioabsorbable support device of example 2 of the invention in an unconstrained state prior to implantation;
FIG. 3 is a schematic view of the bio-absorbable support device being rolled within the conveyor;
FIG. 4 is a schematic view of the conveyor;
FIG. 5 is a schematic view of the delivery sleeve configuration of the transporter;
FIG. 6 is a schematic view of a push rod of the conveyor;
FIG. 7 is a schematic view of a biofilm, the left view being a schematic plan view and the right view being a schematic perspective view;
FIG. 8 is a schematic plan view of the skeletal structure of a nickel titanium alloy wire according to example 1;
FIG. 9 is a schematic plan view of the skeleton structure of the nitinol wire of example 2.
Detailed Description
In order to more clearly illustrate the invention, the invention is further described below in connection with preferred embodiments. It is to be understood by persons skilled in the art that the following detailed description is illustrative and not restrictive, and is not to be taken as limiting the scope of the invention.
The directional terms "upper", "lower", "left" and "right" used herein are used in accordance with the present invention, and are used for convenience of description, and are not intended to limit the structure of the present invention.
The invention relates to a degradable supporting diaphragm device for preventing and treating intrauterine adhesion, which comprises a bioabsorbable supporting device 10 and a matched conveyor 20;
the bioabsorbable support device 10 comprises a biological membrane 11, a nitinol wire framework 12 and a drug coating (not shown); the shape of the biological membrane 11 is matched with the uterine cavity; the nickel-titanium alloy wire framework 12 comprises an embedded section 121 and an extension section 122, wherein the embedded section 121 is embedded into the biological membrane 11 and is used for supporting the biological membrane 11 to be in an expanded state; the drug coating is loaded on the outer surface and/or the inner surface of the biological membrane 11 and is used for promoting the repair of endometrium and preventing adhesion;
the conveyor 20 comprises a pushing rod 21 and a conveying sleeve 22, the conveying sleeve 22 can be sleeved outside the pushing rod 21 in a matching mode, in the pushing process, the bioabsorbable supporting device 10 is placed at the front end of the pushing rod 21, the finger retaining rings 211 are arranged at the rear end of the pushing rod, and the two finger retaining rings 221 are arranged on the outer wall of the conveying sleeve 22.
In some embodiments of the present invention, the material of the biological membrane 11 is one or more of hyaluronic acid, collagen, and polylactic acid. The biological membrane can be degraded and absorbed within 3 months.
In some embodiments of the present invention, before implantation, the biofilm 10 is bound at the front end of the pushing rod 21 in the delivery sleeve 22, and the biofilm is in a coiled tube shape, has a diameter less than or equal to 0.8mm, and can be successfully implanted in the uterine cavity.
In certain preferred embodiments of the present invention, in the post-implantation deployed state, the biofilm member 11 has an inverted triangle shape with a side length of 20mm to 70 mm; the three corners are replaced by arc corners, and the diameter of the arc is 5mm-20 mm; the thickness of the membrane is 1mm-5 mm. It will be appreciated that in the post-implantation deployed state, the shape of the support device is selected to accommodate the physiological shape and dimensions of the uterus while isolating the anterior and posterior walls of the uterus over as full an area as possible, thereby minimizing the chance of contact between the anterior and posterior walls of the uterus. The biological membrane in the shape of an inverted triangle has opposite top and bottom portions, matching the shape of the uterus, with the top portion facing forward prior to implantation.
In certain preferred embodiments of the present invention, the width of the top of the biofilm member in the post-implantation deployed state is 20-70mm, preferably 40-50 mm; the width of the bottom is 5-20mm, preferably 10-15 mm; the distance between the top and the bottom is 10-50mm, preferably 20-40 mm.
In some preferred embodiments of the invention, the embedded section of the nitinol wire framework is embedded into the outer edge of the biological membrane and surrounds the biological membrane, and the distance between the embedded section and the membrane is 3-5 mm. The insertion section of the nitinol wire frame may allow the biofilm to assume an expanded state after implantation.
In certain preferred embodiments of the present invention, the embedded sections of the nitinol wire skeleton are dispersed into 3-8 pieces embedded in the biofilm sheet. The biofilm member may be caused to assume a deployed state after implantation.
In certain preferred embodiments of the invention, the nitinol wire skeleton has a diameter of 0.35mm to 0.89 mm.
In certain embodiments of the invention, the drug coating is comprised of soy phospholipid and an effective drug; wherein, the soybean lecithin is a medicament film-forming auxiliary agent added with a film-coating forming agent on the surface of the biological membrane, which is beneficial to the medicament; the effective medicine comprises one or two of PDGF (platelet derived growth factor) and GM-CSF (granulocyte-macrophage colony stimulating factor) to promote the growth of intima. Under the condition of certain drug concentration and coating thickness, the degradation period of the membrane is combined, so that the drug release time is 7 days to 6 months, preferably 1 month to 3 months. The soybean lecithin: the mass ratio of the medicine is 1: 1.4-1.6.
In certain embodiments of the invention, the PDGF to GM-CSF weight ratio is 10-30: 70-90.
In certain embodiments of the invention, the effective drug loading is between 50-100 μ g.
In certain embodiments of the invention, the drug coating is between 5-30 μm thick.
In some embodiments of the invention, the length scales are arranged on the outer wall of the conveying sleeve of the conveyor, so that the position of the conveyor entering the uterus can be conveniently measured, and the position of the biological membrane implanted into the uterine cavity is more accurate.
In certain embodiments of the present invention, the conveyor material comprises one of 304 stainless steel, 316 stainless steel, Polycarbonate (PC), Acrylonitrile Butadiene Styrene (ABS); the outer diameter of the conveyor is 1.0cm-1.5 cm.
Example 1
The invention relates to a degradable supporting diaphragm device for preventing and treating intrauterine adhesion, which comprises the following components in part by weight:
firstly, collagen raw materials are made into a biological membrane through a freeze-drying process, the thickness of the biological membrane is controlled to be 1.5mm through pressing, and the biological membrane is cut through a die to form the biological membrane with the shape as shown in figure 7; in FIG. 7, dimension A is 5cm, dimension B is 2cm, and dimension R is 8 mm;
then, the nickel-titanium alloy wire with the diameter of 0.35mm is heat-set into the shape shown in figure 8, and then the nickel-titanium alloy wire is inserted into the biological membrane as shown in figure 1. The illustration shows the bioabsorbable support device 10 in an unconstrained state prior to implantation and in an expanded state after implantation in the uterine cavity between the anterior and posterior walls of the uterine cavity; the shape of the inverted triangle is close to the shape of a pear in a uterine cavity, so that the isolation area of the front wall and the rear wall of the uterus is maximized, and adhesion is avoided; wherein the width of the top of the biological membrane 11 is 50mm, the width of the bottom is 20mm, the thickness is 1.5mm, and the distance between the top and the bottom is 40 mm;
spraying the biological membrane inserted with the nickel-titanium alloy wires with a spraying machine, and coating a drug coating on the outer surface of the membrane, wherein the adopted film-forming auxiliary agent is soybean lecithin, the adopted drug is PDGF (platelet derived growth factor) with the dosage of about 60 mu g, and the coating thickness is 5 mu m;
the loaded bioabsorbable support device 10 is placed in a convection oven at 37 ℃ for drying for 15 minutes to allow the solvent content on the stent to evaporate completely.
The biological membrane 11 is coiled into a tubular shape in the jig, as shown in fig. 3, the biological membrane 11 is arranged at the front end of the pushing rod 21 in the conveying sleeve 22 of the conveyor, and the exposed extension section 122 of the biological membrane 11 is left outside the near end along the conveying sleeve, so that the biological membrane 11 can be conveniently and immediately drawn out after being implanted into the uterine cavity;
furthermore, the bioabsorbable support device 10 of this embodiment is constrained in the delivery tube before implantation, and is in a coiled state, as shown in fig. 4, the diameter is less than or equal to 0.8cm, and the device can be delivered smoothly into uterus by a delivery device, so that the operation is convenient; after the nickel-titanium alloy wire framework 12 is self-expanded, the membrane is placed between the front wall and the rear wall of the uterine cavity in a plane shape, and the nickel-titanium alloy wire 12 is extracted out through a conveyor along with the current situation; the biological membrane 11 does not bring obvious discomfort to the patient (compared with other implanted stents and balloons), does not need to be taken out for the second time, is not connected with the outside, and does not have the risk of reversely infecting the uterus.
Example 2
The invention relates to a degradable supporting diaphragm device for preventing and treating intrauterine adhesion, which comprises the following components in part by weight:
as shown in fig. 7, collagen raw material is made into a biological membrane 11 through an electrostatic spinning process, the thickness of the biological membrane is controlled to be 3mm through pressing, and the biological membrane is cut through a die to form the biological membrane in the shape of fig. 7; the size A is 5cm, the size B is 2cm, and the size R is 8 mm;
as shown in fig. 9, a nickel-titanium alloy wire with the diameter of 0.89mm is heat-set into the shape shown in fig. 9, and then the nickel-titanium alloy wire is inserted into the membrane as shown in fig. 2; the illustration shows the bioabsorbable support device 10 in an unconstrained state prior to implantation and in an expanded state after implantation in the uterine cavity between the anterior and posterior walls of the uterine cavity; the shape of the inverted triangle is close to the shape of a pear in a uterine cavity, so that the isolation area of the front wall and the rear wall of the uterus is maximized, and adhesion is avoided; wherein the width of the top of the membrane is 55mm, the width of the bottom is 15mm, the thickness is 3mm, and the distance between the top and the bottom is 45 mm.
Spraying a medicine on the biological membrane 11 inserted with the nickel-titanium alloy wire framework 12 by using a spraying machine, and coating a medicine coating on the outer surface of the biological membrane, wherein the adopted film-forming auxiliary agent is soybean lecithin, the adopted medicine is GM-CSF (granulocyte-macrophage colony stimulating factor), the dosage is about 80 mu g, and the coating thickness is 5 mu m;
drying the stent after carrying the drug in a convection oven at 37 ℃ for 15 minutes to completely volatilize solvent components on the stent;
furthermore, the bioabsorbable support device 10 of this embodiment is constrained in the delivery tube before implantation, and is in a coiled state, as shown in fig. 3, the diameter is less than or equal to 1.0cm, and the device can be delivered smoothly into uterus by a delivery device, so that the operation is convenient; after the nickel-titanium alloy wire framework 12 is self-expanded, the membrane is placed between the front wall and the rear wall of the uterine cavity in a plane shape, and the nickel-titanium alloy wire framework 12 is extracted out along the current through a conveyor; the biological membrane does not bring obvious discomfort to patients (compared with other implanted stents and saccules), does not need to be taken out for the second time, is not connected with the outside and does not have the risk of reversely infecting the uterus.
It should be understood that the above-described embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. Not all embodiments are exhaustive. All obvious changes and modifications which are obvious to the technical scheme of the invention are covered by the protection scope of the invention.
Claims (7)
1. A degradable supporting diaphragm device for preventing and treating intrauterine adhesion comprises a bioabsorbable supporting device and a matched conveyor; the method is characterized in that:
the bio-absorbable support device comprises a biological membrane, a nickel-titanium alloy wire framework and a drug coating; the shape of the biological membrane is matched with the uterine cavity; the nickel-titanium alloy wire framework comprises an embedded section and an extension section, and the embedded section is embedded into the biological membrane and is used for supporting the biological membrane to be in an unfolded state; the extension section is convenient for the biological membrane to be drawn out immediately after being implanted into the uterine cavity; the drug coating is loaded on the outer surface and/or the inner surface of the biological membrane and is used for promoting the repair of endometrium and preventing adhesion;
the conveyor comprises a pushing rod and a conveying sleeve, the conveying sleeve can be sleeved outside the pushing rod in a matching mode, the bioabsorbable supporting device is arranged at the front end of the pushing rod, a finger buckle ring is arranged at the rear end of the pushing rod, and two finger buckle rings are arranged on the outer wall of the conveying sleeve;
the embedded section of the nickel-titanium alloy wire framework is embedded into the outer edge of the biological membrane and surrounds the biological membrane for a circle, and the distance from the embedded section to the membrane boundary is 3-5 mm; or the embedded sections of the nickel-titanium alloy wire framework are dispersed into 3-8 wires which are embedded into the biological membrane sheets; the diameter of the nickel-titanium alloy wire framework is 0.35mm-0.89 mm.
2. The degradable supporting diaphragm device for preventing and treating intrauterine adhesion of claim 1, wherein: the biological membrane is made of one or more of hyaluronic acid, collagen and polylactic acid.
3. The degradable supporting diaphragm device for preventing and treating intrauterine adhesion of claim 1, wherein: before implantation, the biological membrane is bound at the front end of the push rod in the conveying sleeve, and is in a winding tubular shape, and the diameter of the biological membrane is less than or equal to 0.8 cm.
4. The degradable supporting diaphragm device for preventing and treating intrauterine adhesion of claim 1, wherein: in an unfolded state after implantation, the biological membrane is in an inverted triangle shape, and the side length of the triangle is 20-70 mm; the three corners are replaced by arc corners, and the diameter of the arc is 5mm-20 mm; the thickness of the membrane is 1mm-5 mm.
5. The degradable supporting diaphragm device for preventing and treating intrauterine adhesion of claim 1, wherein: in the unfolded state after implantation, the width of the top of the biofilm sheet is 20-70 mm; the width of the bottom is 5-20 mm; the distance between the top and the bottom is 10-50 mm.
6. The degradable supporting diaphragm device for preventing and treating intrauterine adhesion of claim 1, wherein: the drug coating consists of soybean lecithin and effective drugs; the effective drug comprises one or two of PDGF (platelet derived growth factor) and GM-CSF (granulocyte-macrophage colony stimulating factor); the soybean lecithin: the mass ratio of the medicines is 1: 1.4-1.6;
the weight ratio of PDGF to GM-CSF is 10-30: 70-90;
the drug loading of the effective drug is between 50 and 100 mu g;
the thickness of the drug coating is between 5-30 μm.
7. The degradable supporting diaphragm device for preventing and treating intrauterine adhesion of claim 1, wherein: the length scales are arranged on the outer wall of the conveying sleeve of the conveyor, so that the position of the conveyor entering the uterus can be conveniently measured, and the position of the biological membrane implanted into the uterine cavity is more accurate;
the conveyor material comprises one of 304 stainless steel, 316 stainless steel, polycarbonate, acrylonitrile-butadiene-styrene copolymer; the outer diameter of the conveyor is 1.0cm-1.5 cm.
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| US20050171569A1 (en) * | 2000-04-25 | 2005-08-04 | Impres Medical, Inc. | Method and apparatus for creating intrauterine adhesions |
| CN103784244B (en) * | 2012-10-30 | 2016-03-23 | 吴江永元生物科技有限公司 | A kind of intrauterine implant |
| CN203074828U (en) * | 2013-02-01 | 2013-07-24 | 浙江大学医学院附属妇产科医院 | Anti-adhesion membrane for uterine cavity |
| CN203263510U (en) * | 2013-05-10 | 2013-11-06 | 广东省计划生育科学技术研究所 | Uterine cavity adhesion prevention and control apparatus |
| CA2965376A1 (en) * | 2014-10-22 | 2016-04-28 | Jmd Innovation Inc. | Anti-adhesion intrauterine balloon |
| CN105903092A (en) * | 2016-06-23 | 2016-08-31 | 刘芸 | Uterus implant and implanting system for same |
| CN206543197U (en) * | 2016-09-18 | 2017-10-10 | 郑朝宜 | In utero prevent adhesion support |
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Denomination of invention: A biodegradable support membrane device for preventing and treating uterine cavity adhesion Effective date of registration: 20230306 Granted publication date: 20201016 Pledgee: Industrial Bank Limited by Share Ltd. Wuhan branch Pledgor: BAIWEI (WUHAN) MEDICAL TECHNOLOGY CO.,LTD. Registration number: Y2023420000091 |
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