WO2020052136A1 - 一种可降解的可折叠生物羊膜复合修复支架 - Google Patents

一种可降解的可折叠生物羊膜复合修复支架 Download PDF

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Publication number
WO2020052136A1
WO2020052136A1 PCT/CN2018/121627 CN2018121627W WO2020052136A1 WO 2020052136 A1 WO2020052136 A1 WO 2020052136A1 CN 2018121627 W CN2018121627 W CN 2018121627W WO 2020052136 A1 WO2020052136 A1 WO 2020052136A1
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Prior art keywords
polylactic acid
amniotic membrane
foldable
stent
tubular
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PCT/CN2018/121627
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English (en)
French (fr)
Inventor
苗春云
吕虎
彭崇军
滕志强
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江西瑞济生物工程技术股份有限公司
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Priority to US17/043,876 priority Critical patent/US11426294B2/en
Priority to EP18933484.0A priority patent/EP3851079A4/en
Publication of WO2020052136A1 publication Critical patent/WO2020052136A1/zh

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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
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • 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
    • A61F2/844—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents folded prior to deployment
    • 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
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L31/125—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L31/129—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix containing macromolecular fillers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body
    • 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
    • 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
    • A61F2210/0071—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof thermoplastic
    • 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
    • A61F2210/0076—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof multilayered, e.g. laminated structures
    • 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
    • A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001—Designing or manufacturing processes
    • A61F2240/002—Designing or making customized prostheses
    • 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
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0014—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
    • A61F2250/0018—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in elasticity, stiffness or compressibility
    • 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
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0014—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
    • A61F2250/0023—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis differing in porosity
    • 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
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/00772—Apparatus for restoration of tear ducts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing

Definitions

  • the present invention relates to the field of biomedical technology, and in particular, to a multi-purpose degradable foldable biological amniotic membrane composite repair scaffold.
  • Lacrimal duct obstruction diseases refer to a class of diseases with lacrimal duct obstruction (lacrimal stricture or / and occlusion) as the pathological feature and tear leakage as the main clinical manifestations caused by various reasons. According to incomplete statistics, LDOD accounts for about 3% of the ophthalmic outpatients, which is a common and frequently-occurring disease in ophthalmology. Lacrimal duct obstruction may occur in any part of the lacrimal duct. Lacrimal ductal obstruction is a more common type of LDOD, and its incidence is about 16% to 25% of LDOD. The causes of lacrimal ductal obstruction are numerous, mainly including inflammation, trauma, congenital abnormalities, drug-induced, systemic diseases, iatrogenic damage, and degeneration.
  • Treatment methods for lacrimal ductal obstruction mainly include two categories of non-surgical treatment and surgical combined catheterization.
  • Non-surgical treatment methods mainly include lacrimal duct laser, lacrimal punctum expansion, lacrimal duct exploration, lacrimal duct irrigation, and the like.
  • Laser lacrimal duct dredging uses the thermal effect of laser and its blasting effect to carbonize the obstructed part, which is suitable for cases with shorter course, small obstruction range, and no lacrimal sac expansion or atrophy.
  • Non-surgical treatment methods such as dilation of the punctum, lacrimal passage, and lacrimal drainage are simple, but improper operation can easily cause lacrimal punctures, lacrimal mucosal damage, and pseudotract formation.
  • the above four treatment methods mainly use mechanical expansion or burning of the obstructed part of the inner wall of the lacrimal duct to effectively clear the lacrimal duct.
  • the mucous membrane wall of the lacrimal duct after dredging is damaged due to mechanical expansion or thermal burning, forming a certain range of internal wall wounds, and the mucosal layer has not been completely epithelialized.
  • the lacrimal duct The lumen is closed. With the progress of the healing process of the lacrimal canaliculus wound, the adhesion of the wound site or the scar contraction of the lacrimal duct wall in the later stage will cause secondary blockage.
  • lacrimal canaliculoplasty In order to improve the long-term effect after lacrimal canaliculi obstruction, combined treatment is usually used after lacrimal canaliculoplasty or laser shaping to reduce the recurrence rate of lacrimal canaliculi, that is, the lacrimal canaliculi after dredging.
  • the proper lacrimal support is placed in the cavity to mechanically expand and isolate the wound caused by probing. Prevent wound adhesion.
  • Some methods to reduce lacrimal ductal obstruction and re-obstruction after operation are mainly to implant various types of lacrimal stent or lacrimal stick in the lacrimal duct (surgery combined with catheterization treatment).
  • lacrimal canaliculus laser dredging combined with catheterization lacrimal canaliculus catheter combined with 0.02% MMC (mitomycin C) eye drops, lacrimal canaliculotomy combined with catheterization, surgery combined with drug treatment, etc.
  • MMC mitomycin C
  • Silicone tubing is of flexible material with poor conformability. Improper immobilization after placement in the lacrimal ducts causes slippage; lasting to the tube wall The expansion and compression are not only conducive to the regression of inflammation and edema of the inner wall and the repair of the mucosa of the tube wall, but also cause chronic inflammation of the lacrimal canaliculus tube wall.
  • the silicone tube stimulates the lacrimal mucosa to form granulation tissue and wrap the silicone tube, which leads to the pull Difficulty in tube management; long-term indwelling of silicone tubes can also easily cause eversion of the eyelids, which can affect the appearance of the eyelids and the siphonic and tear-guiding functions of the lacrimal duct.
  • Chinese Patent No. 99246881.7 discloses a lacrimal probing device, with metal probes at both ends, a soft silicone tube in the middle, and a smooth stainless steel tube with a metal tip, which is composed of a head end and a long handle.
  • the implantation of the silicone tube stent can support the stoma, and also drain the bleeding and secretions in the lacrimal sac, reduce inflammation and speed up the healing of the wound.
  • the silicone tube stent can be pulled by friction. Damage to the lacrimal duct tissue; adhesion between the catheter and the lacrimal duct wall, secondary damage during extubation, and easy to cause the lacrimal duct to be blocked again.
  • Chinese Patent No. 99246881.7 discloses a lacrimal probing device, with metal probes at both ends, a soft silicone tube in the middle, and a smooth stainless steel tube with a metal tip, which is composed of a head end and a long handle.
  • the implantation of the silicone tube stent can support the
  • 200720005808.4 discloses a lacrimal duct drainage tube, the design enables the product to support the lacrimal duct, and also has the functions of irrigation and drug administration, but the product itself does not It has the function of repair, and the tube needs to be pulled out, which is easy to cause secondary damage.
  • Chinese Patent Application No. 2017110803382 discloses an amniotic lacrimal stent repair stent, which adopts an amniotic stent body made of freeze-dried amniotic membrane, and the sheet-like amniotic membrane is made into a tube, rod or A strip, and a medical suture connected to two ends of the amniotic stent body respectively, and the length of the amniotic stent body between the two suture nodes is slightly larger than the length of the medical suture between the two suture nodes.
  • amniotic lacrimal duct repair stent is simple and time-saving, easy to adapt to the zigzag structure of the lacrimal duct, avoids damage to the lacrimal duct tissue due to pulling friction and secondary blockage caused by adhesion, and has good therapeutic effect on the diseased tissue. It is beneficial for the restoration of lacrimal epithelium function and prevents scar formation.
  • Amniotic membrane is a degradable material without extubation. The long-term effect is good and the recurrence rate is low. Since the amniotic stent body has a constant diameter along its length, it needs to be made into a variety of specifications according to the use site.
  • Intrauterine adhesions also known as Asherman syndrome, refers to the adhesion of the uterine cavity muscle wall and / or cervical canal to each other after damage to the endometrium of the uterine cavity or cervical basement membrane due to various factors, Its harm lies in affecting menstruation and reproductive function of women of childbearing age. Traumatic infections, infections, uterine malformations, and genetic predispositions in the uterine cavity during pregnancy and non-pregnancy are the main causes of uterine adhesions. The main pathological changes of uterine adhesions are endometrial fibrosis and scar formation.
  • intrauterine adhesions often manifest as amenorrhea or menstrual flow reduction, periodic abdominal pain, infertility and placenta implantation after pregnancy, fetal growth restriction, postpartum hemorrhage, etc., which seriously affect the reproductive health of women of childbearing age.
  • Hysteroscopic trans-cervical rescdon of adhesions is a standard procedure for the treatment of intrauterine adhesions.
  • TCRA trans-cervical rescdon of adhesions
  • the endometrial basement membrane is severely damaged. Almost no longer has a regeneration function.
  • the endometrium after the electrosurgical separation is difficult to regenerate.
  • the presence of electrothermal effects during the electrosurgical separation and electrocoagulation during hemostasis makes pathological repair and inflammation of the wounded tissue wounds.
  • Sexual granulation tissue and fibrous scars which in turn caused the adhesion of the exposed anterior and posterior walls of the uterine cavity without endometrium coverage.
  • Effectively promoting the repair of the endometrium and basement membrane is the key to preventing the formation of re-adhesion and treating uterine adhesions. It is also a difficult problem.
  • the main methods of postoperative re-adhesion are: 1 barrier medium method, including the use of intrauterine device and Foley balloon urine Tube.
  • the intrauterine device cannot effectively separate the front and back walls of the uterus, and may cause excessive inflammatory reactions, leading to a large number of inflammatory mediators, promoting the release of adhesion-forming cytokines, and accelerating the formation of re-adhesion after surgery.
  • Patients need to be hospitalized during Foley's balloon ureteral therapy, with the possibility of secondary infection or even cervical insufficiency; the endometrium is difficult to grow when the intrauterine balloon is compressed; this method has a short treatment period and the long-term effect of preventing re-adhesion is still not sure.
  • estrogen and progesterone are routinely administered for 2 to 3 months after IUA separation, or estrogen is used alone.
  • the above measures are effective in preventing re-adhesion after adhesion separation in patients with mild-to-moderate IUA. Menstrual recovery and reproductive prognosis are significantly improved, but the effect of patients with severe IUA is not optimistic, and the re-adhesion rate after surgery can reach more than 50%.
  • Amniotic membrane transplantation after TCR A, the ideal follow-up treatment is to be able to apply a biologically active mechanical barrier to inhibit uterine re-adhesion and promote epithelial regenerative repair.
  • Human fetal amniotic membrane is a natural polymer biological material, which is the most active part of cell growth and differentiation in the placenta. It contains collagen, glycoprotein, proteoglycan, integrin and laminar, and it expresses a variety of growth factors. Its mRNA-related proteins can provide abundant nutrients for cell proliferation and differentiation.
  • amniotic membrane into the uterine cavity can not only serve as a good biological barrier, but also inhibit the inflammatory response, and promote endometrial repair. And growth properties, this repair-promoting property, no better material has been found than amniotic membrane.
  • Intrauterine amniotic implantation and application of amnion tissue engineering materials will become a new method for treating intrauterine adhesions.
  • Patent No. 201110058056.9 discloses a drug-coated stent for preventing and preventing intrauterine adhesions.
  • the stent is woven from a nickel-titanium alloy wire into a palace net basket, and the net basket is coated with a layer of biocompatible film.
  • a slow-release drug-containing layer is sprayed on the outside, and the drug is estrogen plus progesterone.
  • the stent described in this patent is made of a non-degradable material. There is no description on how to remove it after it is sent into the uterine cavity. It is easy to see that the removal of the stent is difficult and may even cause secondary trauma.
  • amniotic cells into the uterine cavity as a kind of carrier barrier material that can be added, rather than adding intact amniotic membrane, so that the material does not have the biological function peculiar to intact amniotic membrane.
  • the technique is to modify the amniotic membrane and take its cells, the modified amnion tissue structure has undergone a fundamental change and no longer has the original regeneration and repair functions.
  • a large number of studies have shown that the amnion basement membrane and the amnion matrix layer contain a large number of differences.
  • Collagen mainly type I, III, IV, V, VII collagen, fibronectin, laminin and other components, and it is these components that make the amniotic membrane act as a "transplanted basement membrane" and play a new healthy fit
  • the matrix acts to promote epithelialization. Tseng believes that the thick basement membrane and avascular matrix that human amnion possesses are the key to successful transplantation. This patent does not have the ideal regeneration and repair function due to the destruction of the tissue structure of the amniotic membrane.
  • the injected barrier material fills the uterine cavity and is blocked with a sphere, poor ventilation in the uterine cavity may not be conducive to the skin's normal breathing, metabolism and wound healing.
  • amniotic membrane with regenerative repair function can be easily transplanted into the uterine cavity after TCRA surgery, and unfolded and attached, and the amniotic membrane support used will not take out the amniotic membrane when taken out. It will cause unnecessary damage to the newborn wounds or cervix, etc., and become the first problem to be solved urgently.
  • the non-degradable material stent as a foreign body, stimulates the lacrimal duct / uterine mucosa, and in severe cases even causes a rejection reaction; 3
  • the stent is improperly fixed after it is placed in the lacrimal duct / uterine cavity.
  • Cause slip 4 Implantation of the stent produces permanent expansion and compression of the tube wall, which is not conducive to the regression of inflammation and edema of the inner wall and repair of the mucosa of the tube wall, hinders normal repair of the tissue, and can cause chronic inflammation of the lacrimal canaliculus / intrauterine wall.
  • the present invention provides a degradable foldable biological amniotic membrane composite repair scaffold.
  • a degradable and foldable biological amniotic membrane composite repair stent comprising a tubular body having an axially extending through hole, a front end of the tubular body having an elastic balloon, said The end of the tubular body is connected to a one-way valve, where the one-way valve closes the through hole, the elastic balloon is disposed in a lumen of a foldable mesh tubular polylactic acid stent, and the foldable mesh tubular poly
  • the outer surface of the lactic acid stent is coated with a biological amniotic membrane, and the mesh of the foldable mesh tubular polylactic acid stent has a plurality of micropores, and the plurality of micropores are filled with a biological amniotic membrane; in an initial state, the elastic balloon The foldable mesh tubular polylactic acid scaffold and the biological amniotic membrane are compressed into a compact state; in the use state, the elastic balloon is injected with sterile gas or liquid to expand into the
  • the foldable mesh tubular polylactic acid scaffold is made of filamentous polylactic acid.
  • the foldable mesh tubular polylactic acid scaffold is made of a polylactic acid material by laser engraving.
  • the foldable mesh tubular polylactic acid scaffold is made of a polylactic acid material by 3D printing.
  • a degradable foldable biological amniotic membrane composite repair stent comprising a tubular body with an axially extending through hole, the front end of the tubular body has an elastic balloon, A check valve is connected to the end of the tubular body, and the check valve closes the through hole there.
  • a sheet-shaped polylactic acid and a sheet-shaped amniotic membrane are laminated and wound on the outer surface of the elastic balloon, and the sheet-shaped polylactic acid has a plurality of micropores, and the plurality of micropores are filled with a biological amniotic membrane; in an initial state, The elastic balloon, sheet-like polylactic acid, and sheet-like amniotic membrane are compressed into a compact state; in the use state, the elastic balloon is injected with sterile gas or liquid to expand into an affected body cavity to adapt to the shape (tubular, drop-like shape) , Or other body cavity characteristics), simultaneously spread the sheet-shaped polylactic acid and sheet-shaped amniotic membrane and attach it to the inner wall of the affected area, and then extract the sterile gas or liquid, and after the elastic balloon shrinks, exit the tubular body .
  • the sheet-shaped polylactic acid has a limit position after being stretched by the elastic balloon, and the sheet-shaped polylactic acid is provided with a locking mechanism for maintaining the limit position.
  • the sheet-shaped polylactic acid is a polylactic acid tablet having a mesh.
  • the present invention has the following beneficial effects:
  • the foldable mesh tubular polylactic acid stent covered with biological amniotic membrane is better adhered to the lacrimal duct wall or the inner wall of the uterine cavity after being stretched, so that the amniotic membrane is promoted.
  • Biological functions such as repairing, reducing scar formation, reducing inflammation, and preventing adhesions can be brought into full play;
  • the foldable mesh tubular polylactic acid scaffold has good strength and stiffness, and can be self-maintained after being stretched, and can be stable.
  • the degradation time of the foldable mesh tubular polylactic acid stent can be selected It can meet the clinical needs.
  • the biological amniotic membrane covering the outer surface of the foldable mesh tubular polylactic acid scaffold is completely degraded, the foldable mesh tubular polylactic acid scaffold is degraded, and the microcapsules filled in the foldable mesh tubular polylactic acid scaffold are filled.
  • the amniotic membrane powder in the hole can continue to slowly play the role of amniotic membrane repair, and continue to maintain a certain biologically active function of the amniotic membrane until the wound is completely healed.
  • the amniotic membrane structure is mainly divided into a basement membrane layer and an amniotic membrane stem cell (the epithelial cell layer is attached to the surface layer of the basement membrane, and the mesenchymal stem cells are dispersed in the basement membrane network structure).
  • the two major parts have a certain elasticity, and the thickness is 0.02 ⁇ 0. .5mm amniotic cells can secrete a large amount of bioactive substances to promote and regulate tissue growth and development.
  • Amniotic membrane can detect more than 150 cell growth regulators and a variety of active proteases, which form a complex network of regulatory mechanisms that work together to regulate cell growth, differentiation and activity, and can regulate local tissue cells at different phases Factor expression and secretion can promote repair and healing of damaged tissues from various aspects.
  • Matrix fibers (type I, III, IV, V, VII collagen) constituting the basement membrane of the amniotic membrane are interwoven into a net,
  • the pore gap is about 0.5 ⁇ 1.5pm ; there are a large number of fibronectin and laminin filling in the pore gap, which are closely combined with collagen fibers through hydrogen bonding, metal chelation, electrostatic attraction and other mechanisms to make the collagen fiber network better.
  • Geoelasticity and toughness and through these mechanisms, a large number of biologically active factors secreted by amniotic stem cells are fixed in the basement membrane network structure and continue to play a biological role.
  • the special biomechanical structure is conducive to cell attachment, growth, and delay, so that the amniotic membrane can act as a "transplanted basement membrane” and play a new healthy and suitable matrix role to promote cell growth.
  • the tubular body of the present invention includes a foldable mesh tubular polylactic acid scaffold and two parts of a complete amniotic membrane wrapped by an outer layer.
  • the polymerization process by adjusting the polymerization process, polymerization time, polymer molecular weight, glycolic acid addition and other key process factors, the degradation time, compliance, support strength characteristics, and integrity of the polylactic acid stent are maintained at 3 ⁇ 6 months can be adjusted to meet relevant needs.
  • the polylactic acid tube maintains good semi-permeability.
  • the pure polylactic acid material has no biological activity to promote tissue repair, and the effect is poor.
  • the amniotic membrane is pulverized into a powder, its particles have a microvilli-shaped morphological structure, which contains a skeleton system composed of collagen fibers, and a large amount of fibrin and laminin are attached between the villi ball fibers. These proteins are highly adhesive. Adherently, small molecule cytokines are firmly fixed in the spherical amniotic membrane powder. However, it is difficult to play an effective role in repairing the wound due to the integrity of the basement membrane.
  • the amniotic membrane powder is filled into the polylactic acid pipe mesh through mechanical pressure to form a composite film.
  • the amniotic membrane powder and the terminal fibers of the amniotic membrane are entangled with the structure of the polylactic acid pipe network.
  • the fibrin and laminin are highly adherent under the body fluid environment. Bonding is integrated with the polylactic acid tube holder. Make it complete Network Structure and Biological Activity of Amniotic Membrane.
  • the present invention wraps a layer of intact amniotic membrane on the outer surface of the foldable mesh tubular polylactic acid stent (in vivo degradation time is about 3 months).
  • the composite structure tubular stent is delivered into the body through a delivery system. Due to the good elasticity and certain rigidity of the tubular body of the stent, the fixation is very stable after implantation and will not slip off, and it is closely attached to the inner surface of the body cavity. According to the characteristics of the recovery process of injury wounds in the body, it is an acute inflammatory recovery process within 3 months. Inflammatory cells infiltrated the injured wounds, a large number of granulation tissues were formed and scars were formed. If there is no stent support, adhesions are extremely easy to occur; 3 months later The gradual inflammation was reduced, and the massive proliferation of granulation tissue was reduced until the tissue was completely repaired.
  • amniotic membrane powder in the micropores of the mesh-shaped polylactic acid scaffold continues to slowly play the role of amniotic membrane repair, and continues to maintain a certain The bioactive function of the amniotic membrane is until the wound is fully healed.
  • the present invention solves the following key problems in the treatment of lacrimal duct obstruction / uterine cavity adhesion: 1
  • Degradable, foldable biological amniotic membrane composite repair stent tubular body is implanted in the lacrimal duct / uterine cavity,
  • the wall / uterine wall has a supporting effect, which effectively prevents the lacrimal duct cavity / uterine wall from closing, avoiding the formation of granulation tissue at the later stage of the wound healing process and the adhesion of tissue caused by the scar contraction of the lacrimal duct / uterine wall;
  • the body is biodegradable, has good biocompatibility, has no stimulating effect on the lacrimal duct / uterine mucosa, and does not cause rejection.
  • the tubular body of the stent has good elasticity and certain rigidity, and it is very stable after implantation. No slippage will occur; 4The implanted stent will gradually degrade with tissue repair, the expansion and compression of the tube wall will be compatible with the tissue repair process, and the stent completely retains the amniotic membrane itself to promote tissue repair, anti-inflammatory, and down-regulate tissue TGF- (31 levels, a variety of biological activities such as anti-fibrosis and inhibition of scar formation, is conducive to reducing the inflammation of the inner wall, Repair of the mucosa of the tube / lumen wall. 5 The degradation time of the tubular body of the degradable stent can be controlled, and it will be completely degraded as the tissue repair is completed.
  • the composite tubular body has good Elasticity and certain rigidity (adjustable according to needs).
  • the pressure balloon can be inflated into different shapes according to needs. After the stent is expanded, it fully conforms to the shape of the lacrimal duct / uterine space and makes full contact with the cavity wall, which is beneficial to bioactive substances or drugs. Enter the organization to make a difference.
  • FIG. 1 is a schematic structural diagram of a degradable foldable biological amniotic membrane composite repair scaffold in an initial state according to the present invention
  • FIG. 2 is a schematic structural view of a degradable foldable biological amniotic membrane composite repair stent in use according to the present invention
  • FIG. 3 is a schematic structural view of a filling body of a degradable, foldable, biological amniotic membrane composite repair stent after it is implanted into an affected area.
  • a degradable foldable biological amniotic membrane composite repair stent comprising a tubular body 1 having an axially extending through hole, a front end of the tubular body 1 having an elastic balloon 2, and an end of the tubular body 1
  • a one-way valve 3 is connected, the one-way valve 3 closes the through hole, the elastic balloon 2 is arranged in the lumen of the foldable mesh tubular polylactic acid stent 4, and the foldable mesh tubular polycondensate
  • the lactic acid stent 4 is made of polylactic acid material by laser engraving.
  • the outer surface of the foldable mesh tubular polylactic acid stent 4 is covered with a biological amniotic membrane 5.
  • the mesh of the foldable mesh tubular polylactic acid stent 4 has several Micropores, several of which are filled with biological amniotic membrane powder; in the initial state, the elastic balloon 2, the foldable mesh tubular polylactic acid scaffold 4, and the biological amniotic membrane 5 are compressed into a compact state; in the use state, The elastic balloon 2 is infused with liquid to expand into an affected area to adapt to the shape. At the same time, the foldable mesh tubular polylactic acid stent 4 is spread out and attached to the inner wall of the affected area, and then the liquid is drawn out. After narrow elastic balloon 2, exits the tubular body 1.
  • a degradable foldable bio-amniotic membrane composite repair scaffold is made by the following method: a degradable polylactic acid material is used to make a foldable mesh tubular polylactic acid scaffold with a number of micropores on a mesh by a laser engraving process, and then The surface of the foldable mesh tubular polylactic acid stent 4 is evenly sprayed with biological amniotic membrane powder, and then the elastic balloon 2 is placed in the lumen of the foldable mesh tubular polylactic acid stent 4, and then a sheet is wrapped on the outer surface of the foldable mesh tubular polylactic acid stent 4.
  • the biological amniotic membrane 5 can be fixed with a medical glue to the foldable mesh tubular polylactic acid stent 4 and then put into the grip press for compression.
  • the compression process is divided into two stages. The first stage adjusts the pressure of the grip press 0.2MPa, holding pressure for 30 minutes, the second stage adjusts the holding press pressure to 0.5MPa, holding pressure for 10 minutes After the compression is completed, it is packed and sterilized to produce a degradable foldable biological amniotic membrane composite repair scaffold.
  • a degradable and foldable biological amniotic membrane composite repair stent comprising a tubular body 1 having an axially extending through hole, a front end of the tubular body 1 having an elastic balloon 2, and an end of the tubular body 1
  • a one-way valve 3 is connected, the one-way valve 3 closes the through hole, the elastic balloon 2 is arranged in the lumen of the foldable mesh tubular polylactic acid stent 4, and the foldable mesh tubular polycondensate
  • the lactic acid scaffold 4 is made of filamentous polylactic acid, and the outer surface of the foldable mesh tubular polylactic acid scaffold 4 is covered with a biological amniotic membrane 5, and the mesh of the foldable mesh tubular polylactic acid scaffold 4 has several micro
  • the elastic balloon 2, the foldable mesh tubular polylactic acid scaffold 4, and the biological amniotic membrane 5 are compressed into a compact state; in the use state, The elastic balloon 2 is injected with sterile gas or liquid to expand the affected area to adapt to the shape.
  • a degradable foldable biological amniotic membrane composite repair scaffold is made by the following method: a filamentous degradable polylactic acid material with several micropores is woven into a foldable mesh tubular polylactic acid scaffold 4, and then the foldable mesh tubular The surface of the polylactic acid stent 4 is evenly sprayed with composite amniotic membrane gel, and then the elastic balloon 2 is placed in the lumen of the foldable mesh tubular polylactic acid stent 4, and the sheet-shaped biological amniotic membrane is wrapped on the outer surface of the foldable mesh tubular polylactic acid stent 4. 5.
  • the bio-amniotic membrane 5 and the foldable mesh tubular polylactic acid stent 4 can be fixed with medical glue, and then put into the grip press for compression.
  • the compression process is divided into two stages.
  • the first stage adjusts the grip press pressure to 0.5MP a.
  • the grip pressure is 15 minutes
  • the grip pressure is adjusted to IMPa in the second stage
  • the grip pressure is 5 minutes.
  • a degradable foldable biological amniotic membrane composite repair stent comprising a tubular body 1 having an axially extending through hole, a front end of the tubular body 1 having an elastic balloon 2, and an end of the tubular body 1
  • a one-way valve 3 is connected, the one-way valve 3 closes the through hole, and a sheet of polylactic acid and a sheet of amniotic membrane are laminated and wound on the outer surface of the elastic balloon 2, and the sheet of polymer Lactic acid has several micropores, and several of the micropores are filled with biological amniotic membranes; in the initial state, the elastic balloon 2, sheet polylactic acid, and sheet amniotic membranes are compressed into a compact state; in the use state, all The elastic balloon 2 is injected with a sterile gas or liquid so that Swell into the affected area to adapt to the shape, at the same time stretch the sheet polylactic acid and sheet amniotic membrane and attach it to the inner wall of the affected area, and then extract the sterile gas or liquid
  • the sheet polylactic acid has an extreme position after being stretched by the elastic balloon 2.
  • the sheet polylactic acid is provided with a locking mechanism to maintain the extreme position.
  • the sheet polylactic acid is made of polylactic acid material through 3D Printed into a polylactic acid sheet with mesh.
  • a degradable foldable biological amniotic membrane composite repair scaffold is made by the following method: 3D printing of a degradable polylactic acid material into a polylactic acid sheet with meshes, and then laser engraving technology on the polylactic acid with meshes Carve several micro-holes on the sheet, and then spread a layer of amniotic membrane fragments evenly on the polylactic acid sheet with mesh, put it into a press, control the pressure, IMPa, and press for 10 minutes; then roll the polylactic acid sheet with mesh and sheet amniotic membrane in a roll Wrap around the outer surface of the elastic balloon, and then put it into the grip press for compression.
  • the compression process is divided into two stages.
  • the first stage adjusts the grip press pressure IMPa, the grip pressure is 10 minutes, and the second stage adjusts the grip pressure.
  • the machine pressure is 2 MPa, and the pressure is held for 3 minutes. After the compression is completed, it is packaged, sterilized, and a degradable foldable biological amniotic membrane composite repair scaffold is prepared.

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Abstract

一种可降解的可折叠生物羊膜复合修复支架，包括具有轴向延伸的贯穿孔的管状本体（1），所述管状本体（1）的前端具有一弹性球囊（2），所述管状本体（1）的末端连接一单向阀（3），所述单向阀（3）在该处封闭所述贯穿孔，所述弹性球囊（2）的外表面包覆有可折叠网管状聚乳酸支架（4），所述可折叠网管状聚乳酸支架（4）的外表面包覆有生物羊膜（5），所述可折叠网管状聚乳酸支架（4）的网丝上具有若干微孔，若干所述微孔中填充有生物羊膜粉；在初始状态下，所述弹性球囊（2）、可折叠网管状聚乳酸支架（4）、生物羊膜（5）被压缩呈紧密状态；在使用状态下，植入体内经加压膨胀后，可顺应泪道管/宫腔形成管状或类水滴状形态或其他体腔相适应空间形态。

Description

一种可降解的可折叠生物羊膜复合修复支架 技术领域
[0001] 本发明涉及生物医学技术领域， 尤其是涉及一种多用途可降解的可折叠生物羊 膜复合修复支架。
背景技术
[0002] 泪道阻塞性疾病 (lacrimal duct obstruction diseases , LDOD)指各种原因引起的以 泪道阻塞 (泪道狭窄或 /和闭塞)为病理特征、 溢泪为主要临床表现的一类疾病。 据 不完全统计， LDOD约占眼科门诊病人量的 3%， 是眼科常见病和多发病。 泪道 的任何部位都有可能发生泪道阻塞， 其中泪小管阻塞作为 LDOD中比较常见的一 种类型， 其发病率约占 LDOD的 16%~25%。 引起泪小管阻塞的病因众多， 主要 有炎症、 外伤、 先天性异常、 药物导致、 系统性疾病、 医源性损伤以及退变等
[0003] 针对泪小管阻塞的治疗方法主要包括非手术治疗和手术联合置管术两大类。
[0004] 非手术治疗方法主要包括泪道激光， 泪点扩张， 泪道探通、 泪道冲洗等。 激光 泪道疏通术采用激光的热效应以及其爆破效果将阻塞部位碳化打通， 适用于病 程较短， 阻塞范围小， 无泪囊扩张或萎缩的病例。 泪点扩张、 泪道探通及泪道 冲洗等非手术治疗方法虽然简便， 但操作不当易造成泪小点豁开、 泪道粘膜损 伤、 假道形成等医源性损伤。 以上四种治疗方式主要通过机械性扩张或烧灼泪 道内壁阻塞部位， 从而达到有效的疏通泪道的目的。 但是， 疏通后的泪道粘膜 壁由于机械扩张或热烧灼受到损伤， 形成一定范围的内壁创面， 粘膜层还未完 全上皮化， 此时如果没有支撑物对泪道管壁的支撑作用， 泪道管腔闭合， 随着 泪小管损伤创面愈合过程的进展， 创面部位会发生粘连或后期泪道管壁形成瘢 痕收缩而造成二次堵塞。
[0005] 为了提高泪小管阻塞术后远期效果， 在泪小管探通或激光成形术后通常采用联 合治疗的方法来降低泪小管阻塞疏通术后的复发率， 即在疏通后的泪小管管腔 内放置合适的泪道支撑物， 对探通造成的创面起到机械性扩张隔离作用， 从而 防止创面的黏连。 5见有的降低泪小管阻塞疏通术后再次阻塞的方法主要是在泪 道中植入各种类型的泪道支架或泪道棒 （手术联合置管术治疗） 。 如泪小管激 光疏通联合置管、 泪小管置管联合 0.02%MMC （丝裂霉素 C） 滴眼液滴眼、 泪小 管切开联合置管术、 手术结合药物治疗等。 这些方法在一定程度上提高了泪小 管阻塞术后的远期效果， 但是泪小管阻塞疏通术后发生再次阻塞的现状仍然存 在， 置管引起的各种并发症 （疏通泪小管阻塞部位的同时会引起泪小管管壁粘 膜不同程度的创面的形成， 以及创伤性炎症水肿的发生； 未完全修复的粘膜内 壁互相黏连以及损伤修复过程中产生瘢痕收缩导致术后再次阻塞； 植入小管与 腔壁粘连， 拔管造成新的创伤， 创面再次粘连而造成泪道管腔再次阻塞） 仍然 没有得到有效的解决， 术后极易发生再次阻塞或狭窄。
[0006] 根据支撑物所用材料不同， 分为丝线、 络肠线、 聚乙烯塑料导管、 金属管， 橡 胶管等， 目前应用最广泛的是硅胶管。 泪道硅胶支架种类较多， 主要有 Crawford 管、 自留式桂胶支架 （self-retaining stent, SRS） 、 双路桂胶导管等； 泪道桂胶 管具有超强弹性和韧性， 受强力牵拉可变成细条形而不断裂等优点。 置硅胶管 的同时也带来了众多弊端， 作为外来异物对皮肤、 眼部结膜及泪道粘膜产生刺 激， 严重者甚至引起排斥反应， 降低患者的依从性； 置入硅胶管操作过程中， 易形成假道或导致泪点劈裂或泪小管撕裂从而导致泪道冲洗不通畅， 导致手术 失败； 硅胶管材质柔韧， 随形性差， 置入泪道后固定不当引起滑脱； 对管壁产 生持久的扩张及压迫不但不利于内壁炎症水肿的消退以及管壁粘膜的修复， 而 且可引起泪小管管壁的慢性炎症反应， 严重者硅胶管刺激泪道粘膜形成肉芽组 织并包裹硅胶管， 进而导致拔管困难； 硅胶管长期留置还易引起眼睑外翻， 从 而影响眼睑外观和泪道的虹吸、 导泪功能。
[0007] 申请号为 99246881.7的中国专利， 公布了一种泪道探通装置， 两端是金属探子 ， 中间为软性硅胶管， 金属探子为光滑的不锈钢小管， 由头端和长柄构成。 硅 胶管支架的植入可以起到支撑造口作用， 同时也可引流泪囊中的渗血及分泌物 ， 减轻炎症， 加快创口的愈合， 但临床实践中发现， 硅胶管支架会因拉动摩擦 而对泪道组织造成损伤； 置管与泪道壁产生粘连， 拔管时形成二次损伤而易造 成泪道再次堵塞等。 [0008] 申请号为 200720005808.4的中国专利， 公布了一种泪道探通引流管， 该设计使 产品具有对泪道管的支撑作用， 同时还兼具冲洗和给药的功能， 但产品本身不 具备修复的功能， 而且管体需要拔出， 易造成二次损伤。
[0009] 申请号为 2017110803382的中国专利， 公布了一种羊膜泪道修复支架， 采用经 冷冻干燥处理的羊膜制成的羊膜支架本体， 片状的羊膜通过搓捻等方式制成管 状、 棒状或条状， 和一根分别连接于所述羊膜支架本体两端的医用缝合线， 两 个缝合线节点之间的羊膜支架本体的长度略大于两个缝合线节点之间的医用缝 合线的长度。 该羊膜泪道修复支架操作简便省时， 易于适应泪道的曲折结构， 避免因拉动摩擦而对泪道组织造成损伤以及粘连而造成二次堵塞， 同时对病变 组织具有较好的治疗功效， 有利于泪道上皮功能的恢复， 防止疤痕形成； 羊膜 为可降解材料而无需拔管， 远期效果好， 复发率低。 由于羊膜支架本体具有沿 其长度恒定的直径， 需要根据使用部位， 制成多种规格产品。
[0010] 宫腔粘连 ( intrauterine adhesions, IUA )又称 Asherman综合征， 是指由于各种因 素所致宫腔或颈管基底膜内膜损伤后， 宫腔肌壁和 /或颈管相互粘连， 其危害在 于影响育龄期女性月经及生育功能。 妊娠及非妊娠时宫腔受到创伤、 感染、 子 宫畸形以及遗传倾向等是形成宫腔粘连的主要原因； 宫腔粘连的主要病理组织 学变化为子宫内膜纤维化及瘢痕形成。 临床上， 宫腔粘连多表现为闭经或月经 量减少、 周期性腹痛、 不孕以及妊娠后胎盘植入、 胎儿生长受限、 产后出血等 ， 严重影响育龄妇女的生育健康。
[0011] 宫腔镜下宫腔粘连切除术 (trans-cervical rescdon of adhesions , TCRA)是宫腔粘 连治疗的标准术式， 然而， 重度宫腔粘连患者， 由于子宫内膜基底膜受到严重 破坏后几乎不再具有再生功能， TCRA中电刀分离后的削面子宫内膜再生困难， 加之术中电切分离及电凝止血时电热效应的存在， 使得受热损伤的组织创面进 行病理性修复并形成炎性肉芽组织及纤维瘢痕， 进而造成裸露的无内膜覆盖的 宫腔前后壁再次粘连。 有效促进子宫内膜基底膜的修复是预防再粘连形成， 治 疗宫腔粘连的重点， 也是难点问题。
[0012] 预防 IUA
术后再粘连的主要方法有： ①屏障介质法， 包括采用宫内节育器和 Foley球囊尿 管。 宫内节育器由于不能有效的分离子宫前后壁， 而且可能引起过度的炎症反 应， 导致大量炎症介质、 促进粘连形成细胞因子释放， 从面加速术后再粘连的 形成。 Foley球囊尿管治疗期间患者需要住院， 有继发感染甚至宫颈机能不全的 可能； 宫腔内球囊压迫的时， 子宫内膜很难生长； 该方法治疗期限短， 预防再 粘连长远疗效尚不肯定。 ②药物治疗， 在 IUA分离术后常规予以雌孕激素序贯 人工周期 2~ 3个月， 或单独应用雌激素。 以上措施在预防轻 -中度 IUA患者粘连 分离术后再粘连形成上效果肯定， 月经恢复及生殖预后均明显改善， 但重度 IUA 患者效果不乐观， 术后再粘连率可达到 50%以上。 近年研究发现， IUA患者血清 雌激素水平无差异的情况下， 粘连组织表面的雌激素受体 (ER) 和转化生长因 子 (31 (TGF-(31) 明显升高， 局部高雌激素水平可能通过提升 TGF -(31等促纤维 化细胞因子的水平， 参与了粘连的发生。 该研究提示， 重度 IUA患者内膜基底 膜破坏严重， 对雌激素缺乏反应的情况下， 一味强调高雌激素水平是否会导致 某些促粘连因子水平上升， 加重再粘连及内膜纤维化的发生。 因此， 雌激素在 重度
IUA患者粘连分离术后再粘连形成中的作用有待进一步探讨。 ③羊膜移植， TCR A后， 理想的后续治疗是能够应用一种有生物活性的机械屏障来抑制宫腔再粘连 和促进上皮再生性修复。 人胎羊膜是一种天然高分子生物材料， 是胎盘中细胞 生长、 分化最活跃的部分， 含胶原、 糖蛋白、 蛋白多糖、 整合素和板层体等多 种成分， 它表达多种生长因子及其 mRNA的相关蛋白， 能为细胞的增殖分化提 供丰富的营养成分， 将羊膜移植到宫腔内， 不仅可作为良好的生物屏障， 还有 抑制炎症反应的作用， 更有促进子宫内膜修复和生长的特性， 这一促进修复的 特性， 目前还没有发现有比羊膜更好的材料。 宫腔内羊膜植人及羊膜组织工程 材料的应用将成为治疗宫腔粘连的新方法。
[0013] 申请号为 201110058056.9 的专利公开了一种防治宫腔粘连的药物带膜支架， 该 支架由镍钛合金丝编织成宫形网篮， 网篮包被一层生物相容膜， 同时膜外喷涂 有缓释载药层， 药物为雌激素加孕酮。 该专利所述的支架是由不可降解的材料 制成， 送入宫腔后如何取出没有说明， 容易看出， 该支架取出困难甚至会造成 二次创伤。 [0014] Amer等 (2006) 尝试为 25例中 -重度 IUA患者行 TCRA术后， 借助 Foley球囊 尿管的支托作用行宫腔内羊膜移植， 试图通过羊膜上皮的再生替代子宫内膜基 底膜， 预防 TCRA术后再粘连形成， 促进月经及生育功能恢复， 取得了一定的 临床效果。 但是球囊在宫腔内呈球形膨大， 该膨大与宫腔内形状不一致， 只有 局部与腔壁接触， 而且羊膜是盲目放入宫腔内的， 放入时由于羊膜太薄， 遇液 体会粘作一团， 不能如愿地展开贴附到宫腔内壁上， 导致手术操作不方便， 羊 膜的作用也不能发挥出来。
[0015] 段华等人提出了关于“一种应用于防治宫腔粘连的载体屏障系统” (CN
102657913A) 的专利申请， 该申请提及将羊膜细胞作为可添加的载体屏障材料 的一种注入宫腔， 而非加入完整的羊膜， 因而导致该材料并不具有完整羊膜所 特有的生物学功能。 由于该技术是对羊膜进行改性， 取其细胞， 改性后的羊膜 组织结构发生了根本变化， 不具再有原来的再生修复等功能， 因为大量研究表 明羊膜基底膜和羊膜基质层含有大量不同的胶原， 主要为 I、 III、 IV、 V、 VII型 胶原和纤维粘连蛋白、 层粘连蛋白等成份， 而正是这些成份使羊膜可以充当“移 植的基底膜”而发挥一种新的健康合适的基质作用来促进上皮化。 tseng认为， 人 羊膜具有的这层较厚的基底膜及无血管的基质是决定移植成功的关键。 该专利 由于破坏了羊膜的组织结构使其并不具有理想的再生修复功能。 另外， 由于被 注入的屏障材料塞满了宫腔并用球体堵塞， 使宫腔内透气性差， 可能不利于皮 肤的正常呼吸、 代谢和创面的修复。
[0016] 由此可见， 将具有再生性修复功能的羊膜在 TCRA手术后较容易地移植到宫腔 内， 并展开、 贴附， 并且采用的羊膜支撑物取出时不会把羊膜带出， 不会对新 生创面或宫颈等造成不必要的损伤成为当前亟待解决的首要问题。
[0017] 综上所述， 目前针对泪道阻塞、 宫腔黏连及相关疾病治疗主要存在以下共性问 题： ①泪道阻塞单纯非手术疏通治疗或宫腔黏连施行宫腔粘连切除术后， 由于没 有支撑物对泪道管壁 /宫腔壁的支撑作用， 泪道管腔 /宫腔壁闭合， 损伤创面愈合 过程中， 创面部位会发生病理性修复， 后期形成肉芽组织或泪道管 /宫腔壁形成 瘢痕收缩而造成黏连； ②不可降解材料支架， 作为外来异物对泪道 /宫腔粘膜产 生刺激， 严重者甚至引起排斥反应； ③支架置入泪道管 /宫腔后固定不当引起滑 脱； ④植入支架对管壁产生持久的扩张及压迫， 不利于内壁炎症水肿的消退以 及管壁粘膜的修复， 阻碍组织正常修复， 可引起泪小管管壁 /宫腔内壁的慢性炎 症反应， 严重者可刺激粘膜形成肉芽组织并包裹植入支架， 进而导致支架取出 困难， 甚至会造成二次创伤； ⑤支架膨大与泪道管 /宫腔内空间形状不一致， 仅 局部与腔壁接触， 不利于生物活性物质或药物进入组织发挥作用。
发明概述
技术问题
问题的解决方案
技术解决方案
[0018] 为解决上述现有技术中所存在的问题， 本发明提供一种可降解的可折叠生物羊 膜复合修复支架。
[0019] 本发明采用如下技术方案实现： 一种可降解的可折叠生物羊膜复合修复支架， 包括具有轴向延伸的贯穿孔的管状本体， 所述管状本体的前端具有一弹性球囊 ， 所述管状本体的末端连接一单向阀， 所述单向阀在该处封闭所述贯穿孔， 所 述弹性球囊设置在可折叠网管状聚乳酸支架的管腔内， 所述可折叠网管状聚乳 酸支架的外表面包覆有生物羊膜， 所述可折叠网管状聚乳酸支架的网丝上具有 若干微孔， 若干所述微孔中填充有生物羊膜； 在初始状态下， 所述弹性球囊、 可折叠网管状聚乳酸支架、 生物羊膜被压缩呈紧密状态； 在使用状态下， 所述 弹性球囊被注入无菌气体或液体从而膨胀成患处体腔适应形状 （管状、 类水滴 状、 或其他体腔性状） ， 同时将所述可折叠网管状聚乳酸支架撑开并贴附于患 处内壁， 然后将无菌气体或液体抽出， 所述弹性球囊缩小后， 退出所述管状本 体。
[0020] 优选的， 所述可折叠网管状聚乳酸支架是由丝状聚乳酸编制而成。
[0021] 优选的， 所述可折叠网管状聚乳酸支架是由聚乳酸材料通过激光雕刻制成。
[0022] 优选的， 所述可折叠网管状聚乳酸支架是由聚乳酸材料通过 3D打印制成。
[0023] 本发明还提供一种替代技术方案： 一种可降解的可折叠生物羊膜复合修复支架 ， 包括具有轴向延伸的贯穿孔的管状本体， 所述管状本体的前端具有一弹性球 囊， 所述管状本体的末端连接一单向阀， 所述单向阀在该处封闭所述贯穿孔， 片状聚乳酸与片状羊膜叠层卷绕在所述弹性球囊的外表面， 所述片状聚乳酸上 具有若干微孔， 若干所述微孔中填充有生物羊膜； 在初始状态下， 所述弹性球 囊、 片状聚乳酸、 片状羊膜被压缩呈紧密状态； 在使用状态下， 所述弹性球囊 被注入无菌气体或液体从而膨胀成患处体腔适应形状 （管状、 类水滴状、 或其 他体腔性状） ， 同时将所述片状聚乳酸与片状羊膜撑开并贴附于患处内壁， 然 后将无菌气体或液体抽出， 所述弹性球囊缩小后， 退出所述管状本体。
[0024] 优选的， 所述片状聚乳酸被所述弹性球囊撑开后具有一极限位置， 所述片状聚 乳酸上设置有保持极限位置的锁定机构。
[0025] 优选的， 所述片状聚乳酸为具有网眼的聚乳酸片。
发明的有益效果
有益效果
[0026] 与现在技术相比， 本发明具有如下有益效果： 包覆有生物羊膜的可折叠网管状 聚乳酸支架被撑开后与泪道壁或宫腔内壁贴合更好， 使羊膜的促进修复、 减轻 疤痕形成、 减轻炎症、 防止粘连等生物学功能得以充分发挥； 可折叠网管状聚 乳酸支架具有很好的强度和硬度， 被撑开后可以自保持撑开后的形状， 可以稳 定的支撑在泪道或宫腔中， 而又不会堵死泪道或宫腔， 从而使泪道或宫腔内保 持畅通， 引流效果更佳； 可折叠网管状聚乳酸支架的降解时间具有可选择性， 可满足临床需求， 当包覆在可折叠网管状聚乳酸支架外表面的生物羊膜被完全 降解后， 可折叠网管状聚乳酸支架降解的同时， 填充在可折叠网管状聚乳酸支 架的微孔内的羊膜粉可以继续缓慢的发挥羊膜的修复作用， 继续保持一定的羊 膜的生物活性功能， 直到创面完全愈合。
[0027] 羊膜结构主要分为基底膜层和羊膜干细胞 （上皮细胞层附于基底膜表层， 间充 质干细胞分散存在于基底膜网状结构中） 两大部分， 具有一定弹性， 厚度 0.02~0 .5mm 羊膜细胞可分泌产生大量的生物活性物质促进和调节组织生长发育。 羊 膜可检测到 150多种细胞生长调节因子和多种活性蛋白酶， 它们形成一套复杂的 网络状调节机制， 协同发挥作用， 调节细胞生长、 分化与活性， 并可在不同时 相调节局部组织细胞因子表达分泌量， 从多方面促进损伤组织修复愈合。 构成 羊膜基底膜的基质层胶原纤维 （I、 III、 IV、 V、 VII型胶原蛋白） 交织成网， 网 孔间隙约 0.5~1.5pm; 网孔间隙中有大量纤维粘连蛋白、 层粘连蛋白填充， 通过 氢键、 金属螯合、 静电吸引等机制与胶原纤维紧密结合在一起， 使胶原纤维网 具有更好地弹性和韧性； 并且通过这些机制， 将羊膜干细胞分泌的大量生物活 性因子固定于基底膜网状结构内持续发挥生物学作用。 特殊的生物力学结构有 利于细胞附着、 生长与迁延， 使羊膜可以充当“移植的基底膜”而发挥一种新的健 康合适的基质作用来促进细胞生长。
[0028] 本公司通过大量研究发现， 羊膜发挥良好的促进组织创面修复、 抑制局部炎症 反应、 机械隔离和防止受伤创面的粘连、 减少和抑制瘢痕形成等效应主要取决 于： ①羊膜基底膜基质结构的完整性是决定羊膜发挥其促组织修复作用的关键； ②大量各种细胞活性因子的存在是发挥作用必不可少的因素； ③在体内保持完整 结构的时限与组织修复过程保持一致 （即在 1~3个月之内的炎性增生期间 （组织 极易发生粘连） 保持有良好的隔离效果） ； ④羊膜支架本体必需与植入的体腔性 状相适应， 羊膜与组织创面保持良好的贴附状态； ⑤支架系统具有良好的半透过 性， 允许气体、 小分子物质通过， 以利于组织呼吸、 代谢产物排出。
[0029] 根据上述研究结果和现有技术存在的问题， 本发明管状本体包括可折叠网管状 聚乳酸支架和外层包裹的完整羊膜两部分。 根据不同病症治疗需要， 通过调节 聚合过程中聚合温度、 时间、 聚合物分子量、 羟基乙酸添加量等关键工艺因素 ， 聚乳酸材料支架降解时间、 顺应性、 支撑强度特性、 支架完整性维持在 3~6个 月时间可进行调控， 满足相关需要。 通过激光雕刻等技术， 加工成含有大量纳 米尺寸的微孔纤维， 聚乳酸管保持良好的半透过性。 但是， 单纯聚乳酸材料不 具备促进组织修复的生物学活性， 效果较差。 羊膜粉碎呈粉末状后， 其颗粒成 微绒毛球状的形态结构， 其含有胶原纤维构成的骨架系统， 并在绒球纤维之间 附着有大量的纤维蛋白、 层粘连蛋白， 这些蛋白有高度的粘附性， 将小分子细 胞因子牢牢固定于球状羊膜粉内。 但是由于基底膜完整性破坏而难以发挥对创 面的有效修复作用。 本发明通过机械压力， 将羊膜粉填充于聚乳酸管网孔内， 形成一个复合膜。 该复合膜在未使用状态， 羊膜粉绒球末端纤维与聚乳酸管网 结构缠绕而牢固结合； 植入体内后， 在体液环境下， 纤维蛋白、 层粘连蛋白的 高度粘附性， 通过多种键合作用与聚乳酸管支架结合为一体。 使之具有完整的 网络结构和羊膜的生物学活性。 但是， 由于所含活性物质低于完整羊膜， 其促 组织修复效应较完整羊膜弱。 为了解决这一问题， 本发明在可折叠网管状聚乳 酸支架外表面在包裹一层完整羊膜 （体内降解时间 3个月左右） 。 该复合结构管 状支架经输送系统送入体内， 由于支架管状本体具有良好的弹性和一定的刚性 ， 植入体内后固定非常稳定不会滑脱， 并与体腔内面紧密贴附。 根据体内损伤 创面恢复过程特点， 3个月内为急性炎性恢复过程， 炎性细胞浸入受损创面， 发 生肉芽组织大量增生和形成瘢痕， 如果没有支架支撑则极易发生粘连； 3个月后 炎症逐渐症减轻， 肉芽组织大量增生减少， 直至组织完全修复， 这一阶段也需 要支架支撑隔离， 不然部分患者也会发生组织粘连。 在支架植入后的 3个月内， 主要由完整羊膜发挥促修复作用， 3个月后则由网管状聚乳酸支架微孔内的羊膜 粉继续缓慢的发挥羊膜的修复作用， 继续保持一定的羊膜的生物活性功能， 直 到创面完全愈合。
[0030] 总之， 本发明解决了泪道阻塞 /宫腔粘连的治疗中的以下关键问题： ①泪道 /宫 腔内植入可降解的可折叠生物羊膜复合修复支架管状本体， 对泪道管壁 /宫腔壁 产生支撑作用， 有效防止泪道管腔 /宫腔壁闭合， 避免了损伤创面愈合过程后期 形成肉芽组织和泪道管 /宫腔壁形成瘢痕收缩造成的组织粘连； ②支架管状本体 为可降解材料， 生物相容性良好， 对泪道 /宫腔粘膜无刺激作用， 不会引起排斥 反应； ③支架管状本体具有良好的弹性和一定的刚性， 植入体内后固定非常稳定 ， 不会出现滑脱； ④植入支架随着组织修复会逐渐降解， 管壁产生扩张及压迫 与组织修复过程相适应， 且支架完全保留了羊膜本身具有的促进组织修复、 抗 炎、 下调组织 TGF -（31水平、 抗纤维化和抑制瘢痕形成等多种生物学活性， 有利 于减轻内壁炎症反应， 促进管 /腔壁粘膜的修复。 ⑤可降解支架管状本体降解时 间可控， 随着组织修复完成而全部降解， 无需取出支架， 避免了支架取出造成 的二次创伤； ⑥复合管状本体具有良好的弹性和一定的刚性 （根据需要可调） ， 压力气囊可根据需要膨胀成不同形状， 支架膨大后完全顺应泪道管 /宫腔内空间 形状， 与腔壁接触全面， 有利于生物活性物质或药物进入组织发挥作用。
对附图的简要说明
附图说明 [0031] 图 1为本发明一种可降解的可折叠生物羊膜复合修复支架初始状态下的结构示 意图；
[0032] 图 2为本发明一种可降解的可折叠生物羊膜复合修复支架使用状态下的结构示 意图；
[0033] 图 3为本发明一种可降解的可折叠生物羊膜复合修复支架植入患处后退出的灌 装本体的结构示意图。
发明实施例
本发明的实施方式
[0034] 下面结合具体实施例对本发明一种可降解的可折叠生物羊膜复合修复支架作进 一步的详细说明。
[0035] 实施例 1
[0036] 一种可降解的可折叠生物羊膜复合修复支架， 包括具有轴向延伸的贯穿孔的管 状本体 1， 所述管状本体 1的前端具有一弹性球囊 2， 所述管状本体 1的末端连接 一单向阀 3 , 所述单向阀 3在该处封闭所述贯穿孔， 所述弹性球囊 2设置在可折叠 网管状聚乳酸支架 4的管腔内， 所述可折叠网管状聚乳酸支架 4是由聚乳酸材料 通过激光雕刻制成， 所述可折叠网管状聚乳酸支架 4的外表面包覆有生物羊膜 5 ， 所述可折叠网管状聚乳酸支架 4的网丝上具有若干微孔， 若干所述微孔中填充 有生物羊膜粉； 在初始状态下， 所述弹性球囊 2、 可折叠网管状聚乳酸支架 4、 生物羊膜 5被压缩呈紧密状态； 在使用状态下， 所述弹性球囊 2被注入液体从而 膨胀成患处适应形状， 同时将所述可折叠网管状聚乳酸支架 4撑开并贴附于患处 内壁， 然后将液体抽出， 所述弹性球囊 2缩小后， 退出所述管状本体 1。
[0037] 可降解的可折叠生物羊膜复合修复支架是通过如下方法制作的： 将可降解聚乳 酸材料通过激光雕刻工艺制作网丝上具有若干微孔的可折叠网管状聚乳酸支架 4 ， 然后在可折叠网管状聚乳酸支架 4表面均匀喷涂生物羊膜粉， 再将弹性球囊 2 放置在可折叠网管状聚乳酸支架 4的管腔内， 再在可折叠网管状聚乳酸支架 4外 表面包裹片状生物羊膜 5 , 可以用医用胶将生物羊膜 5与可折叠网管状聚乳酸支 架 4固定， 再整体放入握压机进行压缩， 压缩过程分为两个阶段， 第一阶段调节 握压机压力 0.2MPa， 握压 30分钟， 第二阶段调节握压机压力 0.5MPa， 握压 10分 钟； 压缩完成后， 包装， 灭菌， 制得可降解的可折叠生物羊膜复合修复支架。
[0038] 实施例 2
[0039] 一种可降解的可折叠生物羊膜复合修复支架， 包括具有轴向延伸的贯穿孔的管 状本体 1， 所述管状本体 1的前端具有一弹性球囊 2， 所述管状本体 1的末端连接 一单向阀 3 , 所述单向阀 3在该处封闭所述贯穿孔， 所述弹性球囊 2设置在可折叠 网管状聚乳酸支架 4的管腔内， 所述可折叠网管状聚乳酸支架 4是由丝状聚乳酸 编制而成， 所述可折叠网管状聚乳酸支架 4的外表面包覆有生物羊膜 5 , 所述可 折叠网管状聚乳酸支架 4的网丝上具有若干微孔， 若干所述微孔中填充有复合羊 膜凝胶； 在初始状态下， 所述弹性球囊 2、 可折叠网管状聚乳酸支架 4、 生物羊 膜 5被压缩呈紧密状态； 在使用状态下， 所述弹性球囊 2被注入无菌气体或液体 从而膨胀成患处适应形状， 同时将所述可折叠网管状聚乳酸支架 4撑开并贴附于 患处内壁， 然后将无菌气体或液体抽出， 所述弹性球囊 2缩小后， 退出所述管状 本体 1。
[0040] 可降解的可折叠生物羊膜复合修复支架是通过如下方法制作的： 将具有若干微 孔的丝状可降解聚乳酸材料编织成可折叠网管状聚乳酸支架 4, 然后在可折叠网 管状聚乳酸支架 4表面均匀喷涂复合羊膜凝胶， 再将弹性球囊 2放置在可折叠网 管状聚乳酸支架 4的管腔内， 再在可折叠网管状聚乳酸支架 4外表面包裹片状生 物羊膜 5 , 可以用医用胶将生物羊膜 5与可折叠网管状聚乳酸支架 4固定， 再整体 放入握压机进行压缩， 压缩过程分为两个阶段， 第一阶段调节握压机压力 0.5MP a, 握压 15分钟， 第二阶段调节握压机压力 IMPa， 握压 5分钟； 压缩完成后， 包 装， 灭菌， 制得可降解的可折叠生物羊膜复合修复支架。
[0041] 实施例 3
[0042] 一种可降解的可折叠生物羊膜复合修复支架， 包括具有轴向延伸的贯穿孔的管 状本体 1， 所述管状本体 1的前端具有一弹性球囊 2， 所述管状本体 1的末端连接 一单向阀 3 , 所述单向阀 3在该处封闭所述贯穿孔， 片状聚乳酸与片状羊膜叠层 卷绕在所述弹性球囊 2的外表面， 所述片状聚乳酸上具有若干微孔， 若干所述微 孔中填充有生物羊膜； 在初始状态下， 所述弹性球囊 2、 片状聚乳酸、 片状羊膜 被压缩呈紧密状态； 在使用状态下， 所述弹性球囊 2被注入无菌气体或液体从而 膨胀成患处适应形状， 同时将所述片状聚乳酸与片状羊膜撑开并贴附于患处内 壁， 然后将无菌气体或液体抽出， 所述弹性球囊 2缩小后， 退出所述管状本体 1 。 所述片状聚乳酸被所述弹性球囊 2撑开后具有一极限位置， 所述片状聚乳酸上 设置有保持极限位置的锁定机构， 所述片状聚乳酸是由聚乳酸材料通过 3D打印 制成具有网眼的聚乳酸片。
[0043] 可降解的可折叠生物羊膜复合修复支架是通过如下方法制作的： 将可降解聚乳 酸材料通过 3D打印制成具有网眼的聚乳酸片， 然后再通过激光雕刻技术在具有 网眼的聚乳酸片上雕刻若干微孔， 再在具有网眼的聚乳酸片上均匀铺一层羊膜 碎片， 放入压力机， 控制压力， IMPa， 压 10分钟； 再将具有网眼的聚乳酸片与 片状羊膜叠层卷绕在所述弹性球囊的外表面， 再整体放入握压机进行压缩， 压 缩过程分为两个阶段， 第一阶段调节握压机压力 IMPa， 握压 10分钟， 第二阶段 调节握压机压力 2MPa， 握压 3分钟； 压缩完成后， 包装， 灭菌， 制得可降解的可 折叠生物羊膜复合修复支架。
[0044] 以上所述仅为本发明的较佳实施例而已， 并不用以限制本发明， 任何熟悉本技 术领域的技术人员在本发明揭露的技术范围内， 可轻易想到的变化或替换， 都 应涵盖在本发明的保护范围的内。 因此， 本发明的保护范围应该以权利要求所 界定的保护范围为准。

Claims

权利要求书
[权利要求 1] 一种可降解的可折叠生物羊膜复合修复支架， 包括具有轴向延伸的贯 穿孔的管状本体， 所述管状本体的前端具有一弹性球囊， 所述管状本 体的末端连接一单向阀， 所述单向阀在该处封闭所述贯穿孔， 其特征 在于， 所述弹性球囊设置在可折叠网管状聚乳酸支架的管腔内， 所述 可折叠网管状聚乳酸支架的外表面包覆有生物羊膜， 所述可折叠网管 状聚乳酸支架的网丝上具有若干微孔， 若干所述微孔中填充有生物羊 膜； 在初始状态下， 所述弹性球囊、 可折叠网管状聚乳酸支架、 生物 羊膜被压缩呈紧密状态； 在使用状态下， 所述弹性球囊被注入无菌气 体或液体从而膨胀成适应患处体腔形状， 同时将所述可折叠网管状聚 乳酸支架撑开并贴附于患处内壁， 然后将无菌气体或液体抽出， 所述 弹性球囊缩小后， 退出所述管状本体。
[权利要求 2] 根据权利要求 1所述的一种可降解的可折叠生物羊膜复合修复支架， 其特征在于， 所述可折叠网管状聚乳酸支架是由丝状聚乳酸编制而成
[权利要求 3] 根据权利要求 1所述的一种可降解的可折叠生物羊膜复合修复支架， 其特征在于， 所述可折叠网管状聚乳酸支架是由聚乳酸材料通过激光 雕刻制成。
[权利要求 4] 根据权利要求 1所述的一种可降解的可折叠生物羊膜复合修复支架， 其特征在于， 所述可折叠网管状聚乳酸支架是由聚乳酸材料通过 3D 打印制成。
[权利要求 5] 一种可降解的可折叠生物羊膜复合修复支架， 包括具有轴向延伸的贯 穿孔的管状本体， 所述管状本体的前端具有一弹性球囊， 所述管状本 体的末端连接一单向阀， 所述单向阀在该处封闭所述贯穿孔， 其特征 在于， 片状聚乳酸与片状羊膜叠层卷绕在所述弹性球囊的外表面， 所 述片状聚乳酸上具有若干微孔， 若干所述微孔中填充有生物羊膜； 在 初始状态下， 所述弹性球囊、 片状聚乳酸、 片状羊膜被压缩呈紧密状 态； 在使用状态下， 所述弹性球囊被注入无菌气体或液体从而膨胀成 患处体腔适应形状， 同时将所述片状聚乳酸与片状羊膜撑开并贴附于 患处内壁， 然后将无菌气体或液体抽出， 所述弹性球囊缩小后， 退出 所述管状本体。
[权利要求 6] 根据权利要求 5所述的一种可降解的可折叠生物羊膜复合修复支架， 其特征在于， 所述片状聚乳酸被所述弹性球囊撑开后具有一极限位置 ， 所述片状聚乳酸上设置有保持极限位置的锁定机构。
[权利要求 7] 根据权利要求 5所述的一种可降解的可折叠生物羊膜复合修复支架， 其特征在于， 所述片状聚乳酸为具有网眼的聚乳酸片。
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