WO2010022640A1

WO2010022640A1 - Integrative urethra sling

Info

Publication number: WO2010022640A1
Application number: PCT/CN2009/073459
Authority: WO
Inventors: 徐国风; 徐斌; 童晓文
Original assignee: 广东冠昊生物科技股份有限公司
Priority date: 2008-08-27
Filing date: 2009-08-24
Publication date: 2010-03-04
Also published as: CN101396292B; CN101396292A

Abstract

An integrative urethra sling is comprised of a sling (1) and two punctured fixing heads (2) respectively fixed to two ends of the sling. The sling (1) is a porous membrane belt or a braided belt with the width of 5-20 mm and the length of 40-120 mm. The punctured fixed head (2) is a warhead body with barbs, which only can move forward and can not back up. A method for making the integrative urethra sling includes the following steps: animal tissues are taken as raw material, treated by epoxy cross-linking fixation, antigen on multi-aspect, mechanics modification, and inducement activity modifying and the like, and then the sling (1) or the punctured fixing heads (2) are made.

Description

Integrated urethral sling

The invention relates to a medical device for treating stress urinary incontinence in women, belonging to an implanted medical device. Background technique

Women's stress urinary incontinence is a common disease among middle-aged and elderly women. The incidence rate is more than 30% among women over 50 years old. The current surgical treatment methods are urethra and bladder neck suspension, and there are many applications for suspension surgery. A urethral sling. These urethral slings are mostly made of synthetic materials, which are complicated in structure and cumbersome to operate. It is made into a rucksack type, and it is made into a long belt type, and some are fixed by surgical sutures. Some that do not need to be sutured have to be fixed by the side sling of the sling. To do this, the side sling of the sling is made hard and sharp, and it is easy to break into the vagina or bladder. It must be pulled by a curved needle that is 15~18cm long, and the sling is pulled to the abdominal wall. The path of the sputum is too long and the damage is large. If it is improperly operated, the bladder may be injured. Based on years of clinical practice and research experience, we have designed a simpler surgical procedure and a more advanced urethral sling to effectively overcome the above drawbacks. Summary of the invention

SUMMARY OF THE INVENTION The object of the present invention is to overcome the deficiencies in the prior art described above and to provide an integrated urethral sling which is safe, reliable, reasonable in structure and convenient to use.

In order to achieve the above object, the integrated urethral sling of the present invention has the following structure: consisting of a suspension strap and two piercing fixing heads respectively fixed at both ends of the suspension strap; any one of the piercing fixed heads is sharp at the front end and has a front half The warhead body of the crucible, the direction of the collapse is directed to the tail of the piercing fixed head, and the suspension strap is connected to the tail of the piercing fixed head.

The integrated urethral sling of the present invention is made entirely of natural biological materials, and comprises a sling made of a porous film tape or a woven tape having a length of 4 to 10 cm and a width of 0.5 to 2.0 cm and two slings fixed at both ends of the sling. Wear a fixed head. The wearing head is similar to a warhead with a squatting head. It is hard before application and can be worn by soft tissues such as fascia, muscles, ligaments, etc. Due to the effect of the squatting, it can only advance, can not be reversed, and can be fixed where it is pushed. After it enters the human body, it absorbs body fluids. After 2 hours, the warhead body and the inverted sputum soften and swell, no longer smash through the tissue, only act like a fixing screw, and quickly close together with the surrounding tissue, it can be firmly Secure the sling. The end of the piercing head is a smooth cylinder, about 2 to 5 mm long, which is used to connect with the surgical operator for operation by a matching operator.

The film sling and the piercing and fixing head are made of animal tendon and membrane tissue, and are prepared by biochemical treatment and processing such as epoxy cross-linking fixation, multi-directional antigen removal, mechanical modification and induction activity modification. It has high stability, is not easy to degrade, has good biocompatibility, and is immune to immune rejection. It can induce the acceptor fiber tissue to grow into it and eventually become Its own fibrous tissue. The preparation steps are as follows: animal fascia, tendon pretreatment, defatting, decellularization, epoxy fixation, multi-directional addition, antigen mechanical modification, processing, induction, activity modification

The pretreatment described in the preparation step herein refers to immersing the raw material for 30 minutes with a broad-spectrum sterilizing agent, washing, and removing impurities such as attached muscles and fat.

The degreasing described in the preparation step refers to extracting the fat remaining in the raw material with an organic solvent. Usable organic solvents are anhydrous ethanol, ethyl acetate, chloroform, acetone, diethyl ether and the like.

Decellularization as described in the preparation step refers to removal of cells in the raw material tissue by enzymatic hydrolysis and detergent method. The enzyme used in the enzymatic hydrolysis method is pepsin or trypsin; the detergent used in the detergent method is Triton xl00, Tris. Hydrochloric acid buffer ten EDTA, OP-10, Tween and so on.

The epoxy fixation treatment described in the preparation step refers to crosslinking and fixing the protein molecules which are basic compositions of the material by epoxide crosslinking, so as to be stable and not easily decomposed or degraded by microorganisms, and the epoxide used is as shown in the following formula:

R—CH——CH,

o , where R = C _n H _2n+1 - or is, n = 0, 1, 2, 3-12.

The multi-directional antigen removal described in the preparation step refers to the application of various organic reagents, blocking specific active groups which cause immunogenicity and changing specific isoforms which cause immunogenicity. The organic reagents which block specific active groups are mainly nucleophiles which are easily reacted with a H ₂ , -OH, and a SH in a protein molecule, such as a carboxylic acid anhydride, an acid chloride, an amide, an epoxide or the like. The reagents that change the specific isomer are mainly strong hydrogen bond forming agents such as terpenoids.

The mechanical modification described in the preparation step refers to a method of chemically modifying or physically modifying a material to have the physical characteristics required for the article. Here, chemical modification is to improve the mechanical strength and rigidity and flexibility by means of crosslinking or grafting; physical modification is to obtain the required treatment by high pressure, vacuum, cryogenic, freeze drying, sonication, etc. Physical characteristics.

The processing described in the preparation step refers to cutting the above-mentioned processed film into a shape of "1" as shown in FIG. 1 and punching it to form a harness assembly; and the hardened and shaped tendon as shown in FIG. In the shape of 2", the cutting is trimmed into a warhead body with a collapsed head, that is, it is necessary to wear a fixed head. Then, the two ends of the sling are wrapped around the tail of the piercing fixed head. A 2 to 4 mm cylinder is placed at the end for connection to the surgical operator. The article shown in Fig. 2 was processed in this manner.

The induction activity modification described in the preparation step is directed to the introduction of an adherent (enriched) growth factor and cell activity into the preparation. Sexual substance. These active substances are some specific polypeptides or glycosaminoglycan complexes. These specific polypeptides are mainly lysine-containing oligopeptides (polypeptides composed of only one amino acid are called oligopeptides) and peptides containing arginine-glycine aspartate peptides, such as Lai (16). Gan Yi Jing Yi Gan is a polypeptide composed of half cysts in one day. Glycosaminoglycans are a class of mucopolysaccharides including hyaluronic acid, chondroitin sulfate, cortisol sulfate, keratan sulfate, heparin, heparan sulfate. The introduced methods include coupling, chemical adsorption, physical adsorption, coating, and collagen membrane coating.

The packaging and sterilization described in the preparation step is a conventional blister pack and sterilized by conventional sterilization to make it a ready-to-use sterile product.

Compared with other existing urethral slings, the "integrated urethral sling" of the invention has the advantages of: it integrates the current urethral sling through the sling, traction, fixation and suspension, and has the function of wearing and fixing. The perforating fixation head is directly inserted into the obturator muscle and the obturator fascia, and does not need to be worn to the abdominal wall, which greatly shortens the path of the perforation and reduces the wound. The sputum fixation head is specially treated, and it is hard to be inserted as a sputum needle. It can be inserted into any tissue other than the bone. After 1 to 2 hours after implantation, it can be softened and swelled by the shackle and the sputum is softened and expanded. The tissue is pierced and only acts like a suture screw, and it is quickly brought together with the surrounding tissue to securely hold the strap in place. More importantly, the entire urethral sling including the sacral fixation head is made of natural biomaterials mainly composed of collagen fibers. It is highly effective and antigen-removing, has high biocompatibility and high stability. Slowly induce the growth of the fibrous tissue of the host, and fix the suspension state of the urethra with its own fibrous tissue. Another specific aspect of the product of the present invention is that it is simple in operation and high in safety.

Of course, the suspension strap and the piercing and fixation head can also be made of existing medical synthetic materials. DRAWINGS

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic view showing the assembly split structure of the urethral sling of the present invention.

Fig. 2 is a schematic view showing the structure of a urethral sling in which the suspension belt is a porous membrane.

Figure 3 is a schematic view showing the structure of a urethral sling in which the sling is a woven mesh. detailed description

The invention will now be further described with reference to the accompanying drawings and embodiments. Embodiment 1:

Take fresh membrane tissue (including lipid net membrane, aponeurosis, pericardium) and tendon of pig or cattle, immerse in 0.1% benzalkonium solution for 30 minutes, remove, remove impurities such as attached fat muscles, wash; Into the degreasing device, extract the fat present in the membrane and the sputum tissue with isoamyl isobutyrate as the organic solvent, take it out, wash it; In the cell reactor, add pepsin and trypsin at a concentration of 120 mg / liter, digest the solution for 4 to 16 hours, remove and wash; put in an epoxy fixed reactor, put in epoxy t-hexane, the concentration is 0.1 N~1.0N, make the reaction for 24~96 hours, take out, wash; put into the antigen reactor, first add the concentration of 1%-10% of the t-valeryl chloride nucleophile, and let the reaction for 4~12 hours, medium And excess acid chloride, washed, and then added with a concentration of 2% ~ 8% of guanidine hydrochloride, the reaction for 8 ~ 24 hours, removed, washed; placed in the mechanical toughening reactor, added to the concentration of 2.5 12.8% of iso-di The acid anhydride is allowed to react at 5 to 10 ° C for 12 to 24 hours to carry out reasonable crosslinking and toughening. It is taken out, washed, dried, and pressurized to form a film made of a membrane structure and a rod made of tendon tissue.

The film is cut into the shape of the sling according to the specification and punched to obtain the sling 1 . Suspension belt 1 is in the form of a film strip, the length is in the range of 40~120mm, and the width is in the range of 5~20mm; there are many holes 11 on the suspension belt, and both ends of the suspension belt are straps 12 perpendicular to the main body of the suspension belt, and are used for Wear the fixed head 2 to connect. The bar is then cut and trimmed in the shape of the piercing head 2 shown in Fig. 1. The piercing fixed head 2 is in the shape of a bullet head, the front end of which is sharp, the front half has a inverted shackle 23, and the direction of the squat is directed to the tail of the piercing fixed head; the tail is a cylinder, and the front half of the cylinder is machined with a circular concave The groove 22 is for connecting with the suspension belt 1. The rear end of the cylinder is a smooth section 21 of about 2 to 5 mm long for easy operation of the surgical operator. The strap 12 is wrapped around the recess 22 of the fixed cylinder, and the fixing method may be bonding, ligating or stitching, so that the suspension strap 1 and the piercing fixed head 2 are integrally connected, as shown in FIG. Show.

The product obtained in Figure 2 was washed and placed in an inductively active modified reactor, and added with 16 lysine and glycine-arginine-glycine-aspartate-serine-valine-cysteine. The polypeptide active material and the carbodiimide coupling agent are allowed to react for 8 to 24 hours, taken out, washed, freeze-dried, packaged, and sterilized. Embodiment 2:

As shown in FIG. 3, this embodiment differs from the first embodiment in that the medical polypropylene material is manufactured by the following method: processing into a film or a woven mesh by medical polypropylene, and cutting into a width of 10 mm, long A sling 1 with a T-shaped lacing of 100 mm at both ends, for which the film strip is to be perforated. By inserting or molding into the piercing and fixing head 2 as described in Embodiment 1, the suspension tape is wrapped around the tail groove of the piercing fixing head 2, and is welded and fixed by ultrasonic welding to obtain as shown in FIG. Products, packaging, sterilization, that is.

The above-mentioned embodiments are preferred embodiments of the present invention, and the claims of the present invention are not limited, and any other modifications or other equivalent substitutions that do not depart from the technical solutions of the present invention are included in the present invention. Within the scope of protection.

Claims

Claim

1. An integrated urethral sling, characterized in that: it is composed of a suspension strap and two piercing fixed heads respectively fixed at two ends of the suspension strap; any one of the piercing fixed heads has a sharp front end and a front half with a reverse The warhead body of the crucible, the direction of the collapse is directed to the tail of the piercing fixed head, and the suspension strap is connected to the tail of the piercing fixed head.

The integrated urethral sling according to claim 1, wherein the sling or/and the shackle fixing head are made of a natural biomaterial mainly composed of collagen fibers.

3. The integrated urethral sling of claim 1 or 2, wherein the method of preparing comprises the steps of:

A. The animal's membrane tissue and tendon are used as raw materials to disinfect and remove impurities;

B. extracting the fat remaining in the raw material with an organic solvent;

C, removing cells in the raw material tissue;

D. The epoxide is cross-linked with the collagen molecules in the raw material to make it stable and not easily decomposed or degraded by microorganisms;

E. Applying an antigen-removing agent to react with a raw material after cross-linking fixation, blocking a specific active group that causes immunogenicity, and changing a specific isoform that causes immunogenicity;

F. The method of chemically modifying or physically modifying the membrane tissue material and the tendon tissue material obtained in the E step, respectively, so as to have the required strength, hardness and flexibility;

G. The sling tape is made of the film structure material processed as described above, and the tendon tissue material processed by the above is mechanically processed to form a piercing fixed head, and the piercing fixed head is fixed at both ends of the sling band;

H, introducing an active substance capable of adhering growth factors and cells to the shaped product;

I. Sterilization, packaging.

The integrated urethral sling according to claim 3, wherein in the step B, degreasing is carried out using anhydrous ethanol, ethyl acetate, chloroform, acetone or diethyl ether as an organic solvent; in the step C, Decellularization is achieved by enzymatic hydrolysis and elution of cells in the membrane tissue and tendon tissue with pepsin or trypsin; in the step D, the epoxide used is selected from the epoxy reagents represented by the following formula: ² , R = C _n H _2n+1 - or 2, η = 0, 1, 2, 3 - 12; in the step Ε, the reagent used to block the specific group is an acid anhydride, an acid chloride, an amide or an epoxide The reagent for changing the specific isomer is a terpenoid.

The integrated urethral sling according to claim 3, wherein: the mechanical modification described in the step F refers to improving the toughness and hardness of the material by chemical modification and physical modification; The modification mainly uses a crosslinking agent to crosslink the linear molecules of the material into a network structure; the physical modification is mainly deep cooling, vacuum and high pressure treatment to make it hard and shaped; the chemically modified crosslinking agent is mainly a dianhydride. Diacid chloride, diacid diamine, diepoxide difunctional reagent.

The integrated urethral sling according to claim 3, wherein: in the step H, the adhesion-promoting growth factor and the active substance of the cell are mainly lysine-containing oligopeptides and arginine-containing ones. A complex of a polypeptide or glycosaminoglycan of a glycine aspartate peptide; the method of introduction is chemical adsorption, physical adsorption, spraying or coupling with a coupling agent.

7. The integrated urethral sling according to claim 1, wherein: the sling or/and the shackle fixing head are made of a medical synthetic material.

8. The integrated urethral sling according to claim 1, wherein: said sling is a film strip or woven tape having a plurality of small holes.

9. The integrated urethral sling according to claim 1, wherein: the sling has a width of 5 to 20 mm and a length of 40 to 120 mm.

10 . The integrated urethral sling according to claim 1 , wherein: the tail of the piercing fixed head is a cylinder, and the outer circumference of the first half of the cylinder has an annular groove; the rear half of the cylinder is a smooth column. Segment, the length of the smooth section is

2~5mm; both ends of the suspension strap have a strap perpendicular to the main body of the suspension strap, and the strap is wrapped around the annular groove of the cylinder to realize the connection between the suspension strap and the piercing fixed head.