CN112494189A - Degradable metal uterine cavity stent and release system and use method - Google Patents
Degradable metal uterine cavity stent and release system and use method Download PDFInfo
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- CN112494189A CN112494189A CN202011212872.6A CN202011212872A CN112494189A CN 112494189 A CN112494189 A CN 112494189A CN 202011212872 A CN202011212872 A CN 202011212872A CN 112494189 A CN112494189 A CN 112494189A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- 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
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- 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
- A61F2/95—Instruments specially adapted for placement or removal of stents or stent-grafts
- A61F2/958—Inflatable balloons for placing stents or stent-grafts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00011—Metals or alloys
- A61F2310/00035—Other metals or alloys
- A61F2310/00041—Magnesium or Mg-based alloys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00011—Metals or alloys
- A61F2310/00035—Other metals or alloys
- A61F2310/00083—Zinc or Zn-based alloys
Abstract
A novel degradable metal uterine cavity stent, a release system and a use method. The stent mainly adopts zinc and alloy thereof, iron and alloy thereof, magnesium and alloy thereof, has good strength and plasticity, can provide stable mechanical support in service period, can be completely degraded after service period, and does not need to be taken out by secondary operation. The support is carved by laser, the thickness of the support is 50-150 mu m, and the coverage rate of the support is 10% -20%. The shape of the expanded uterine cavity support conforms to the uterine cavity, and the expanded uterine cavity support is 3-8 cm high, 2-5 cm wide and 0.2-1 cm thick. The slow-release medicine film on the surface of the stent contains epidermal growth factors, estrogen and antibiotic medicines, can accurately act on endometrium, reduces the toxic and side effects of the medicines, promotes the growth of the endometrium and avoids uterine cavity infection. The release system is made of nylon or polyethylene glycol terephthalate, has no biological toxicity, can be removed after the uterine stent is expanded, has no catheter residue, and avoids bacterial infection from the lower genital tract to the upper genital tract. The device of the invention can meet the use requirements of the human body uterine cavity bracket.
Description
Technical Field
The invention relates to a design and preparation method of a biodegradable medical device, in particular to a novel degradable metal uterine cavity stent and a release system and a use method thereof.
Technical Field
The intrauterine adhesion refers to the mutual adhesion of cervical canal and uterine wall after the tissue structure of endometrial basement is damaged and the intima loses the regeneration function due to radiotherapy, intrauterine operation, low estrogen state, infection and the like, and is a common reason for amenorrhea, infertility, menstrual flow reduction, periodic abdominal pain, premature birth, spontaneous abortion, abnormal embryo planting and the like of women of childbearing age, so that the fertility right of women of proper age is greatly damaged, and the current national population policy is not facilitated. The method for treating intrauterine adhesion, which is widely accepted by scholars at home and abroad, is hysteroscopic intrauterine adhesion decomposition (TCRA) combined with postoperative intrauterine physical barrier placement and oral estrogen complex therapy. In the early stage of endometrial scar repair of a patient within 1 month after an adhesion decomposition operation, the conditions of granulation hyperplasia, inflammatory exudation, membranous adhesion formation and the like generally exist. Statistics about 62.5% of patients after TCRA surgery develop intrauterine re-adhesion, and therefore prevention of intrauterine re-adhesion after surgery has been the focus of clinical studies.
The main current solution is to place an intrauterine device (IUD) in the uterus after surgery, water sac in the uterine cavity and administer oral estrogen artificial cycle therapy. In clinical application, the shape of the intrauterine device can not be completely matched with the shape of the uterine cavity, and the wound surfaces of the front wall and the rear wall of the uterus can not be completely separated, so that adhesion occurs again. Meanwhile, copper ions contained in the contraceptive ring have an inflammation-causing effect and are not beneficial to the growth of endometrium, so that the clinical application of the contraceptive ring has certain limitation. The mechanical barrier function can be realized by the implantation of the uterine cavity saccule, and the Foley's ureteral head water sac is generally selected to be used as the uterine cavity water sac, so that the cost is low, but the ellipsoidal water sac cannot be matched with the shape of the uterine cavity; the balloon of the imported Cook company is in a triangular shape which is basically equal to the physiological shape of the uterus of a patient, can ensure that the edge of the uterine cavity and the uterine horns at two sides of the uterine cavity of the patient can be effectively separated, but has higher cost. The intrauterine pressure of the implanted water sac is not well controlled, and the local pressure is too high, which can cause the ischemia necrosis of the intima. And the saccule is communicated with the outside by a catheter, in order to reduce infection, the placement of the saccule does not exceed 1 week generally, and the preventive anti-infection treatment is needed in the re-placement process. In addition, after the implant is implanted into a uterine cavity water sac or an intrauterine device, oral administration of high-dose estrogen is required to be matched, and the systemic application of high-dose estrogen has the risk of increasing venous thrombosis. In conclusion, the scheme adopted to reduce the recurrence possibility of the postoperative intrauterine adhesion of the patient is a key topic of current clinical attention.
Disclosure of Invention
In order to solve the problems of poor effect, postoperative re-adhesion and foreign technical monopoly of the existing medical instruments for preventing uterine adhesion, the invention aims to design a novel degradable metal uterine cavity stent, a release system and a use method so as to meet the requirements.
A novel degradable metal uterine cavity stent and release system is characterized in that: the degradable metal uterine cavity stent is attached with a release system, can be placed into a uterine cavity through toothless forceps in a contraction state, and then is expanded into an inverted triangle-shaped uterine-like shape through the release system. Can provide stable mechanical support for more than 30 days after being released in the uterine cavity, particularly form a physical barrier at the uterine horn and the edge and separate intrauterine adhesions intima. The release system comprises a uterine shaped air bag, a conduit and a one-way inflation valve. The uterus-shaped air bag is a hollow isosceles triangle structure, one end of the conduit is connected and communicated with the vertex angle end of the uterus-shaped air bag and is used for air in the inflation process or water in the water filling process to enter the uterus-shaped air bag from the conduit, and the other end of the conduit is connected with the one-way inflation valve; the one-way inflation valve comprises an inflation valve and a pressure gauge, the pressure gauge is arranged at one end, connected with the guide pipe, of the one-way inflation valve and used for monitoring the pressure of the uterine cavity-shaped air bag in real time, and the inflation valve is arranged at the other end of the one-way inflation valve and used for inflating and avoiding air leakage.
Furthermore, the height of the filled uterus-shaped air bag is 5-6 cm, the bottom edge of the uterus-shaped air bag is 3-5 cm, and the thickness of the uterus-shaped air bag is 1-2 cm.
Furthermore, the stent is an air bag expansion stent, is tightly attached to the endometrium when released, avoids sliding and falling off, only acts on the functional layer of the endometrium, and does not affect the basement layer of the endometrium. The uterine cavity stent is prepared by a laser cutting process, and then is subjected to grinding, welding and electrolytic polishing. The uterine cavity bracket is provided with a series of models according to the difference of the sizes of the human uterus, and the size of the uterine cavity is determined by the detection depth of the probe. The expanded uterine cavity support is in shape conforming to the uterine cavity, is pressed on the endometrium through the expansion of the air bag, and is better fixed in the uterine cavity through the compressive stress generated by plastic deformation, so as to avoid displacement or separation. Previous data show that the normal unobstructed uterine cavity pressure is less than 16kPa, the blocked uterine cavity pressure is between 16 and 25kPa, and therefore, the supporting force of the degradable metal uterine cavity support is between 10 and 26 kPa.
Further, the thickness of the uterine cavity stent is 50-150 μm, and the coverage rate of the stent is 10% -20%; the height of the whole expanded uterine cavity stent is 3-8 cm, the width is 2-5 cm, and the thickness is 0.2-1 cm.
Furthermore, the degradable metal materials needed for manufacturing the uterine cavity stent are respectively zinc and alloy thereof, iron and alloy thereof, and magnesium and alloy thereof, and the uterine cavity stent is characterized in that the zinc alloy comprises the following chemical components: at least one of Li, Mg, Ca, Sr, Mn, Fe, Ag, Co, Cr, Ti, Sn, Si, Se and Ge, 0.1-1.5 wt% of Li, 0.01-9.9 wt% of Mg, 0.01-5.8 wt% of Ca, 0.01-9.5 wt% of Sr, 0.01-8.5 wt% of Mn, 0.01-6.1 wt% of Fe, 0.01-10.5 wt% of Ag, 0.01-6.4 wt% of Co, 0.01-4.4 wt% of Cr, 0.01-4.8 wt% of Ti, 0.01-5 wt% of Sn, 0.01-5 wt% of Si, 0.01-5 wt% of Se, 0.01-5 wt% of Ge and the balance of Zn. The chemical components of the iron alloy are as follows: at least one of Mg, Ca, Sr, Mn, Zn, Ag, Co, Ti, Sn, Si, Se and Ge, and 0.01-5 wt% of Mg, Ca, Sr, Mn, Zn, Ag, Co, Ti, Sn, Si, Se and Ge, and the balance of Fe. The magnesium alloy comprises the following chemical components: at least one of Li, Ca, Sr, Mn, Zn, Ag, Co, Cr, Ti, Sn, Si, Se and Ge, 0.1-6 wt% of Li, 0.01-3 wt% of Ca, 0.01-1 wt% of Sr, 0.01-5 wt% of Mn, 0.01-3 wt% of Zn, 0.01-10 wt% of Ag, 0.01-5 wt% of Co, 0.01-2 wt% of Ti, 0.01-15 wt% of Sn, 0.01-36 wt% of Si, 0.01-10 wt% of Se, 0.01-5 wt% of Ge and the balance of Mg.
The metal material has good biocompatibility. Wherein, magnesium is a macroelement of human body, and zinc and iron are microelements necessary for human body, and participate in various life activities in human body. In addition, the zinc element can enhance the sperm activity and is beneficial to the postoperative pregnancy of patients. The degradable metal uterine cavity stent is mainly biologically safe Zn ions, Fe ions and Mg ions after being degraded in the uterine cavity environment, and a small amount of corrosion products can be discharged out of the body through metabolism and menstruation.
Furthermore, the mechanical support of the novel degradable metal uterine cavity stent is closely related to the structural design of the novel degradable metal uterine cavity stent. The invention provides a selection principle of a bracket material, which comprises the following steps: the yield strength of the degradable material is more than 200MPa, the tensile strength is higher than 300MPa, the elongation is more than 20%, and the yield strength after 1 month of degradation is higher than 150 MPa. The degradation rate of the degradable scaffold material is as follows: the degradation rate is lower than 0.02mm/y within 1 month before implantation, the degradation rate is between 0.02mm/y and 0.5mm/y after implantation for 1 to 3 months, and the degradation rate is higher than 0.5mm/y after implantation for 3 months and is gradually degraded. The in vitro cell biotoxicity of the degradable scaffold material is grade 1.
Furthermore, the novel degradable metal uterine cavity stent is characterized in that an estrogen slow-release drug film can be selectively coated on the surface of the stent according to the condition of a patient, the slow-release drug film is prepared by mixing a drug and a carrier and coating the mixture on the stent or using a porous coating for slow release, the carrier is mainly degradable polymers, including PLA, PGA, poly propyl acetate and the like, and the drug is epidermal growth factor, estrogen and antibiotic drug. The estrogen can promote rapid growth and recovery of endometrium, maintain integrity of endometrium, reduce factor denuded due to damaged endometrium basal layer, and protect myometrium tissue; meanwhile, the property of cervical mucus can be changed, the cervical mucus is reduced and sticky, bacteria can be prevented from ascending, and pelvic infection is prevented. Epidermal Growth Factor (EGF) is an autocrine and paracrine factor for regulating the growth and differentiation of endometrial cells, and has a stimulating effect on the proliferation of endometrial gland epithelial cells and interstitial cells. Antibiotics such as gentamicin, penicillin, streptomycin and the like are locally and slowly released, so that the effective drug concentration can be achieved in the uterine cavity with small dose, the antibiotics can be continuously released in the period of implantation, the infection is effectively prevented, the toxic and side effects of systemic medication are avoided, the occurrence of endometrium infectious inflammation is reduced, the postoperative infection can be effectively prevented, and the re-adhesion rate is reduced.
Furthermore, the material of the release system is nylon or polyethylene terephthalate, and the release system has no biotoxicity.
According to the novel degradable metal uterine cavity stent and the use method of the release system, air enters the uterine cavity-shaped air bag through the guide pipe by the aid of the release system through the inflation valve, the air injection speed is 4-8 ml/min, the pressure gauge senses the pressure of the uterine cavity-shaped air bag, the uterine cavity-shaped air bag is expanded, the stent is attached and fixed to the uterine cavity, inflation is carried out when the air pressure displayed by the pressure gauge is lower than 12-24 KPa, and the release system stops immediately when the air pressure is higher than 24 KPa. Subsequently, the balloon is deflated and the entire delivery system is removed.
The invention has the following beneficial effects:
1. the release process of the uterine cavity bracket after the device is inflated is one-time operation, the expanded shape conforms to the uterine cavity, effective support and isolation are formed on uterine horns and edges of the uterine cavities, sliding can be avoided, pressure is uniformly distributed, over-high pressure is not generated on local parts, and the occurrence of adhesion of the uterine cavities and uterine horn parts thereof is effectively prevented.
2. The pressure gauge on the inner side wall of the uterine type air bag can sense the pressure of the air bag, and researches show that 24KPa is an intermediate value of critical pressure of uterine rupture caused by pain, the pressure is adjusted to be less than 12-24 KPa according to individual difference, so that necrosis caused by embedding the bracket into endometrium under overhigh pressure is prevented, and the bracket in the uterine cavity is not fully expanded or even falls off caused by overlow pressure. The air bag belongs to a part of the release system and does not need to be placed in the uterus, so that the air bag does not need to be taken out in a secondary operation, and the burden of the patient on hospitalizing again can be reduced.
3. The novel degradable metal uterine cavity stent adopts biodegradable metal and has good strength and plasticity. The corrosion is uniform and slow within 1 month after the implantation, and the stable mechanical support property can be kept. After 3 months of implantation, the corrosion is accelerated until the corrosion is completely degraded, and corrosion products and metal ions formed in the period can be discharged out of the body along with metabolism and menstrual process and do not accumulate in the uterine cavity.
4. The slow-release medicine film on the periphery of the novel degradable metal uterine cavity stent is prepared by mixing medicines and carriers, coating the medicines and the carriers on the stent or using a porous coating for slow release, wherein the carriers mainly comprise degradable polymers, including PLA, PGA, poly propyl acetate and the like, and the medicines comprise epidermal growth factors, estrogen and antibiotic medicines. The medicine is not lost in the implantation process, the medicine slow release effect is obvious, the medicine absorption time is about 2-3 weeks, and enough medicine local support time is provided, so that the medicine concentration in the uterine cavity is kept constant, and the toxic and side effects of the medicine are reduced; and the biocompatibility is good, and the self-absorption can be completely realized.
5. The novel degradable metal uterine cavity stent peripheral slow-release drug completely and directly acts on the surface of a uterine cavity wound, avoids large-dose continuous administration of oral estrogen and long-time whole-body application of antibiotics, reduces damage to liver and kidney, reduces the risk of thrombosis, and increases the local action effect of the drug; reduces the physiological and economic burden of the patient and effectively reduces the occurrence of the re-adhesion of the endometrium. The novel degradable metal uterine cavity stent and the release system thereof have extremely high popularization value and wide application prospect in the field of treating uterine cavity adhesion, and are very favorable for promoting and ensuring the childbirth safety of women.
Drawings
Fig. 1(a) is a schematic view of a degradable uterine stent after expansion of a release system, and (b) is a sectional view of the view in fig. (a).
FIG. 2 is a schematic view of the delivery system of the device of the present invention: (a) before the system is released, and (b) after the system is released.
FIG. 3 is a schematic view of the implantation process of the device of the present invention: (a) a uterine cavity with uterine adhesions, (b) an implanted contracted uterine stent and balloon, (c) an expanded uterine stent and balloon, (d) a balloon-removed uterine stent.
Detailed Description
In order to make the technical solution of the present invention more apparent, the present invention is further described in detail with reference to the following examples. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1: the structural design of a novel degradable metal uterine cavity stent and a release system thereof.
As shown in figure 1, the device structure of the invention comprises a uterine cavity bracket and a release system, and is used for treating the uterine adhesion.
The novel degradable metal uterine cavity stent and the release system have the following structures: the thickness of the uterine cavity bracket is 50-100 mu m. (figure 1) according to the size of the uterus of a human body, the expanded uterine cavity support is 3-8 cm high, 2-5 cm wide and 0.2-1 cm thick, and the shape of the uterine cavity support conforms to the shape of the uterine cavity. The uterine cavity bracket is composed of two parts (1 and 2) (figure 1a) and respectively acts on the uterine cavity and the uterine horn part, and the part 2 is connected to the part 1 through welding. As can be seen from the cross-sectional view of the uterine cavity stent (fig. 1b), the thickness of the stent is thicker in the part away from the cervical part of the uterus, and the density of the support body is higher, so that higher stress can be borne when the stent is released, and larger deformation can be obtained at the same time.
The uterine cavity release system (figure 2) comprises a uterine shaped air bag, a catheter and a one-way inflation valve; the uterus-shaped air bag is a hollow isosceles triangle structure body, the height of the filled uterus-shaped air bag is 5-6 cm, the bottom edge of the uterus-shaped air bag is 3-5 cm, and the thickness of the uterus-shaped air bag is 1-2 cm; one end of the catheter is connected and communicated with the vertex angle end of the palace-shaped elastic balloon stent; the one-way inflation valve comprises an inflation valve and a pressure gauge and is used for sensing the pressure of the palace-shaped elastic saccule support, and the inflation valve is arranged at the other end of the one-way inflation valve and is used for inflating and avoiding air leakage (figure 2 b). When the uterus stent needs to be expanded, the inflation valve injects air into the uterus-shaped air bag through the catheter, so that the uterus-shaped air bag expands and drives the uterus cavity stent to expand, the pressure gauge controls the expansion of the air bag and controls the attachment of the uterus cavity stent and the uterus cavity (figure 2 b).
The implantation process of the uterine cavity stent comprises the following steps: when the stent and the air bag are in a contraction state, the air bag is positioned in the stent (figure 1b), is placed into a uterine cavity through a vagina, and is subjected to fine adjustment and correction on the positions of the branches and the main body part of the stent by using toothless forceps under the assistance of ultrasound so as to be positioned in the corresponding channels; the bracket is inflated in the uterine cavity through the air bag to expand into a uterine shape and is fixed in the uterine cavity; finally, the air sac is withdrawn, and only the uterine cavity stent is left in the uterine cavity.
The uterine cavity stent is coated with a slow-release medicine film, the slow-release medicine film is made of PLA, and epidermal growth factors, estrogen, chitosan and antibiotic medicines are contained in the slow-release medicine film and used for stimulating the growth of endometrium.
Example 2: preparation of novel degradable metal uterine cavity stent
The preparation method of the novel degradable metal uterine cavity branch comprises the following steps: selecting a medical degradable metal uterine cavity stent material → laser cutting → grinding → welding → electropolishing.
Firstly, selecting Mg-3 wt% Zn, Zn-0.8 wt% Li and pure Fe pipes as medical degradable metal uterine cavity stent materials, wherein the diameter of each pipe is 2-5 cm, and the thickness of each pipe is 50-150 mu m; the yield strength of the material is 220-400 MPa, the tensile strength is 350-600 MPa, and the elongation is 20-90%.
And secondly, performing laser cutting on the selected pipe to form a uterine cavity support, welding and assembling different parts after polishing, and finally performing electrolytic polishing to obtain the uterine cavity support with the height of 3-8 cm, the width of 2-5 cm and the thickness of 50-150 mu m. The measured radial supporting force of the degradable metal uterine cavity support is 15-26 kPa, and the support can be used for effectively and mechanically supporting the adhesion endometrium.
Example 3: degradable uterine cavity stent animal in-vivo implantation experiment
Adult mature female Shanghai white pigs suffering from uterine adhesion are selected as degradable uterine cavity stent implantation objects, and a degradable uterine cavity stent and a release system with proper sizes are designed and prepared according to the uterine body size (the length is 1-1.5 cm, and the width is 1.5-3 cm) of the adult female Shanghai white pigs, wherein the degradable stent is prepared from Zn-0.8Li alloy. The uterine cavity stent and the release system can be placed in the uterine cavity by the toothless forceps in a contraction state, then expanded into a uterus-like shape by the release system, and respectively implanted for 1, 2, 3 and 6 months and then taken out for observation.
After operation, the shape of the degradable uterine cavity stent is conformed to the uterine cavity after expansion, and effective support isolation is formed on uterine horn and uterine cavity edge. The degradable uterine cavity stent is uniformly and slowly corroded within 1 month after being implanted, and can keep stable mechanical support, and the degradation rate in the period is 0.01-0.02 mm/y; the degradation rate is 0.02-0.4 mm/y within 1-3 months after implantation; the corrosion is accelerated after the implant is implanted for 3 months, and the degradation rate is 0.6-0.8 mm/y. Until complete degradation after 6 months, no residual corrosion products were found in the uterine cavity during implantation.
The slow-release effect of the medicine is obvious during the implantation of the stent, the growth of endometrium is obviously accelerated, and meanwhile, the infection of uterine cavity is not seen. Pathological analysis is carried out on the liver and kidney of the implant, and no inflammatory reaction is seen. The degradable uterine cavity stent is proved to have good biocompatibility.
Claims (10)
1. A degradable metal uterine cavity stent and release system is characterized in that: the degradable metal uterine cavity stent is attached with a release system, the stent can be placed in a uterine cavity through toothless forceps in a contraction state, and then is expanded into an inverted triangle-shaped similar uterine shape through the release system; can provide stable mechanical support for more than 30 days after being released in the uterine cavity, particularly form a physical barrier at the uterine horn and the edge to separate intrauterine adhesion intima; the release system comprises a uterine shaped air bag, a conduit and a one-way inflation valve; the uterus-shaped air bag is a hollow isosceles triangle structure, one end of the conduit is connected and communicated with the vertex angle end of the uterus-shaped air bag and is used for air in the inflation process or water in the water filling process to enter the uterus-shaped air bag from the conduit, and the other end of the conduit is connected with the one-way inflation valve; the one-way inflation valve comprises an inflation valve and a pressure gauge, the pressure gauge is arranged at one end, connected with the guide pipe, of the one-way inflation valve and used for monitoring the pressure of the uterine cavity-shaped air bag in real time, and the inflation valve is arranged at the other end of the one-way inflation valve and used for inflating and avoiding air leakage.
2. The degradable metallic uterine stent and delivery system of claim 1, wherein: the height of the filled uterus-shaped air bag is 5-6 cm, the bottom edge of the uterus-shaped air bag is 3-5 cm, and the thickness of the uterus-shaped air bag is 1-2 cm.
3. The degradable metallic uterine stent and delivery system of claim 1, wherein: the uterine cavity stent is an air bag expansion stent, is tightly attached to the endometrium when released, avoids sliding and falling off, only acts on the functional layer of the endometrium, and does not influence the basement layer of the endometrium; the uterine cavity stent is prepared by a laser cutting process, and then is subjected to grinding, welding and electrolytic polishing; the uterine cavity bracket is provided with a series of models according to the difference of the sizes of the human uterus, and the size of the uterine cavity is determined by the detection depth of the probe; the expanded uterine cavity support conforms to the shape of the uterine cavity, is pressed on the endometrium through the expansion of the air bag, and is better fixed in the uterine cavity through the compressive stress generated by plastic deformation so as to avoid displacement or separation; previous data show that the normal unobstructed uterine cavity pressure is less than 16kPa, the blocked uterine cavity pressure is between 16 and 25kPa, and therefore, the supporting force of the degradable metal uterine cavity support is between 10 and 26 kPa.
4. The degradable metallic uterine stent and delivery system of claim 1 or 3, wherein: the thickness of the uterine cavity stent is 50-150 mu m, and the coverage rate of the stent is 10% -20%; the height of the whole expanded uterine cavity stent is 3-8 cm, the width is 2-5 cm, and the thickness is 0.2-1 cm.
5. The degradable metallic uterine stent and delivery system of claim 1 or 3, wherein: the degradable metal materials needed in the manufacturing of the uterine cavity stent are respectively zinc and alloy thereof, iron and alloy thereof, and magnesium and alloy thereof, wherein the zinc alloy comprises the following chemical components: at least one of Li, Mg, Ca, Sr, Mn, Fe, Ag, Co, Cr, Ti, Sn, Si, Se and Ge, wherein Li is 0.1-1.5 wt%, Mg is 0.01-9.9 wt%, Ca is 0.01-5.8 wt%, Sr is 0.01-9.5 wt%, Mn is 0.01-8.5 wt%, Fe is 0.01-6.1 wt%, Ag is 0.01-10.5 wt%, Co is 0.01-6.4 wt%, Cr is 0.01-4.4 wt%, Ti is 0.01-4.8 wt%, Sn is 0.01-5 wt%, Si is 0.01-5 wt%, Se is 0.01-5 wt%, Ge is 0.01-5 wt%, and Zn is the balance; the chemical components of the iron alloy are as follows: at least one of Mg, Ca, Sr, Mn, Zn, Ag, Co, Ti, Sn, Si, Se and Ge, and the content of Mg, Ca, Sr, Mn, Zn, Ag, Co, Ti, Sn, Si, Se and Ge is 0.01-5 wt%, and the balance is Fe; the magnesium alloy comprises the following chemical components: at least one of Li, Ca, Sr, Mn, Zn, Ag, Co, Cr, Ti, Sn, Si, Se and Ge, 0.1-6 wt% of Li, 0.01-3 wt% of Ca, 0.01-1 wt% of Sr, 0.01-5 wt% of Mn, 0.01-3 wt% of Zn, 0.01-10 wt% of Ag, 0.01-5 wt% of Co, 0.01-2 wt% of Ti, 0.01-15 wt% of Sn, 0.01-36 wt% of Si, 0.01-10 wt% of Se, 0.01-5 wt% of Ge and the balance of Mg.
6. The degradable metallic uterine stent and delivery system of claim 1 or 4, wherein: the mechanical support of the degradable metal uterine cavity stent is closely related to the structural design thereof; the selection principle of the bracket material is as follows: the yield strength of the degradable material is more than 200MPa, the tensile strength is higher than 300MPa, the elongation is more than 20%, and the yield strength after 1 month of degradation is higher than 150 MPa; the degradation rate of the degradable scaffold material is as follows: the degradation rate is lower than 0.02mm/y within 1 month before implantation, the degradation rate is between 0.02mm/y and 0.5mm/y after implantation for 1 to 3 months, and the degradation rate is higher than 0.5mm/y after implantation for 3 months and is gradually degraded; the in vitro cell biotoxicity of the degradable scaffold material is grade 1.
7. The degradable metallic uterine stent and delivery system of claim 1 or 5, wherein: the degradable metal uterine cavity stent can be selectively coated with an estrogen sustained-release drug film on the surface according to the condition of a patient, the sustained-release drug film is prepared by mixing a drug and a carrier and coating the drug on the stent or using a porous coating for sustained release, the carrier is mainly degradable polymers, and comprises PLA, PGA and poly propyl acetate, and the drug is epidermal growth factor, estrogen and antibiotic drug; the estrogen can promote rapid growth and recovery of endometrium, maintain integrity of endometrium, reduce factor denuded due to damaged endometrium basal layer, and protect myometrium tissue; meanwhile, the property of cervical mucus can be changed, the cervical mucus is reduced and sticky, bacteria can be prevented from ascending, and pelvic infection is prevented.
8. The degradable metallic uterine stent and delivery system of claim 1 or 5, wherein: the Epidermal Growth Factor (EGF) is an autocrine and paracrine factor for regulating the growth and differentiation of endometrial cells, and has a stimulating effect on the proliferation of endometrial gland epithelial cells and interstitial cells; the antibiotics comprise gentamicin, penicillin and streptomycin, can reach effective drug concentration in uterine cavity in small dose through local slow release, can be continuously released during implantation, effectively prevent infection, simultaneously avoid toxic and side effects of systemic medication, reduce occurrence of endometrium infectious inflammation, effectively prevent postoperative infection and reduce re-adhesion rate.
9. The degradable metallic uterine stent and delivery system of claim 1 or 5, wherein: the release system is made of nylon or polyethylene terephthalate and has no biotoxicity.
10. The use method of the degradable metal uterine cavity stent and the release system according to claim 1, wherein the release system uses an inflation valve to introduce air into the uterine cavity balloon through the conduit, the air injection speed is 4-8 ml/min, the pressure gauge senses the pressure of the uterine cavity balloon to expand the uterine cavity balloon and make the stent and the uterine cavity fit and fixed, when the air pressure displayed by the pressure gauge is lower than 12-24 KPa, the inflation is carried out, and when the air pressure is higher than 24KPa, the stop is immediately carried out; subsequently, the balloon is deflated and the entire delivery system is removed.
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