CN103239265B - Anastomat for gastrointestinal tract anastomosis surgery and production method thereof - Google Patents
Anastomat for gastrointestinal tract anastomosis surgery and production method thereof Download PDFInfo
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- CN103239265B CN103239265B CN201310175656.2A CN201310175656A CN103239265B CN 103239265 B CN103239265 B CN 103239265B CN 201310175656 A CN201310175656 A CN 201310175656A CN 103239265 B CN103239265 B CN 103239265B
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Abstract
The invention provides an anastomat for gastrointestinal tract anastomosis surgery and a production method thereof. The anastomat comprises an anastomosis nail and a base and is divided into two types, namely a combined type and an independent type. The anastomat is composed of degradable materials and medical barium sulfate and can be finally disintegrated to be powder to be removed from the body after being used up. An envelope is formed on the outer surface of the anastomat through polyacrylic resin and contains medicines such as sulfonamides and quinolones antisepsis and anti-inflammation medicines and adrenobazonum, dicynone and other hemostasis medicines, and the envelope can selectively perform medicine slow release and controlled release according to different pH physiological environments of gastrointestinal tracts.
Description
Technical field
The present invention relates to a kind of medical apparatus and instruments, particularly a kind of gastrointestinal tract stapler, be mainly used in the gastral end to end anastomosis such as the stomach of human body, small intestinal, large intestine, end-to-side anastomosis and side to side anastomosis operation.
Background technology
Operation stitching is the conventional surgery operating technology tissue cut or wound ruptures, organ being carried out involutory or rebuild its passage, recover its function, ensure good healing.1881, Billroth for successfully completing first case manual suture operation, and manual suture technology is progressively full-fledged subsequently, is seamed to one of important basic operative techniques technology.The histoorgan of different parts needs in different ways or method is sewed up, and simple stitching is usually used in the stitching of skin, subcutaneous tissue, muscle, aponeurosis (aponeuroses); Everting suture keeps edge of wound inner face level and smooth, is usually used in the stitching of blood vessel, peritoneum, lax skin; Inverting suture keeps level and smooth outside edge of wound, is usually used in the stitching of intestinal, bladder.1908, Hungary doctor Hultl and Fisher invented stiching instrument.Surgery company of the U.S. (Auto Suture) founder Leon Hirsh invention titanium nail anastomat in 1967, and make titanium nail anastomat realize commercially producing, mechanical stitch technograph has landmark meaning.Current commercial product has: EEA surgical stapler, anastomosis ring applicator, linear anastomat, line style Endo-GIA, arc incision anastomat, hemorrhoid anastomat, purse-string suture device, skin fascia stiching instrument.1892, Murphy doctor invented identical button (Murphy button).1976, Hardy doctor invented anastomosis ring.(see reference document 1).
The gastrointestinal tract of Clinical practice method of coincideing has manual suture, the stitching of metal anastomotic device, anastomosis ring to fasten this three kinds of methods.Manual suture is with a long history, is a kind of suturing skill using suture to repair wound.This technical operation is more loaded down with trivial details, and suture time is depending on surgical experience, and general needs 30 minutes, in addition, the repeated localised puncture of suture is comparatively large to gastrointestinal tissue damage, adds the probability that the generation of postoperative enteritis and granuloma etc. occur.Along with the appearance of Titanium nail anastomat, be born a kind of Sutureless anastomosis of novel utilization operating theater instruments.This anastomat operates more convenient, and sewing up mouth more can standardization control.But after operation recovery from illness, leaving over of Titanium nail can affect the inspection such as postoperative X ray, CT, MRI.Meanwhile, titanium nail remains in the periphery of suture site, reduces gastrointestinal elasticity, is unfavorable for the wriggling of intestinal, add anastomotic stoma cicatrix, probability that stenosis of bowel blocks.Anastomosis ring is then that utilization two annulus developing out on Sutureless anastomosis interlock the anastomat that principle makes.
The medical treatment consumptive materials made with degradable high polymer materials such as the homopolymer of Acetic acid, hydroxy-, bimol. cyclic ester, lactide, caprolactone, trimethylene carbonate, Lanthanum Isopropoxide or copolymers at present or apparatus (stitching thread, hemostatic clamp, bone anchor etc.) show huge application and economic potential.In order to meet the specific demand of medical field, various macromolecular material product that is blended or copolymerization development constantly occurs.The medical application of PGA (PGA) or polylactide (PLA), includes but are not limited to these:
(1) for pure PGA or pure PLA.
Solid articles: nail, bone screw, hone lamella, bone substitute (such as: mandibular prostheses), operation needle, impermanent implantable intrauterine device, interim drainage tube or test conduit, Vascular implant or support, stitching thread etc.
Fibre: burn dressing, hernia patch, Absorbable rod paster, wound surface gauze or fabric, sthptic sponge, tourniquet bandage, anti-adhesion membrane, dental care bag etc.
Other: burn or wound thin slice or powder, Absorbable rod foam, thin film coatings prosthetic appliance etc.
(2) for the blended goods of PGA, PLA and other material.
Solid articles: the ion exchange resin of slowly degraded, reinforced nail, bone rod etc.
Fibre: arterial graft or substitute, skin surface binder, burn dressing (using in conjunction with other thin polymer films).
The advantage of set of the present invention stitching method and the method for fastening, designs a kind of novel Sutureless anastomat, and this anastomat adopts manual or mechanical manner operation, anastomat two parts are combined, two parts connect in the mode of anastomosis staple, operate easier, connect more firm.
The present invention has selected widely used medical degradable material PGA, polylactide to be raw material, then to coordinate with medical development agent, makes anastomat, is applied to gastrointestinal tract and coincide.The function that this anastomat has easy, can develop.Here it should be noted that, the size of this anastomat can be improved according to the size of body lumen, is designed to the gastrointestinal anastomosis device being not only applicable to stomach, small intestinal, large intestine, can also be applicable to the tube chamber anastomat that esophagus, tremulous pulse, vein etc. coincide, early stage supports.
This anastomat loads various anti-inflammation haemostatic medicament by coated medicine-carried system, slow release and the controlled release of medicine is carried out in the physiological environment (stomach pH1-3.5, small intestinal pH5-7, large intestine pH8.3-8.4) of the different pH of human body, make the anastomat only with gastrointestinal tract anastomosis bracket function, develop into the multi-functional anastomats be integrated in one such as there is postoperative anti-inflammation, hemostasis, give full play to its potential, realize " a tractor serves several purposes, a device multipotency ".
Prior art document
List of references 1: publication number is the United States Patent (USP) of US3974835A.
Summary of the invention
the problem that invention will solve
The invention provides a kind of gastrointestinal tract stapler of novel structure, this anastomat set advantage of multiple anastomosis, comprise the base of anastomosis staple assembly and the flat annular bodily form in hollow.Anastomat is divided into combination type and stand alone type two kinds.Anastomat can be made up of degradation material and medicinal barium sulfate.
The invention provides a kind of gastrointestinal tract stapler of disintegratable, disintegration time can be controlled in certain limit, by through time disintegrate become broken powder, eliminate fragment corner angle damage intestinal and remain in the possibility of intestinal corner.
The invention provides a kind of gastrointestinal tract stapler with anti-inflammation anastalsis, it can be combined the medicines such as sulfonamides, quinolones, carbazochrome salicylate, etamsylate.Sulfonamides, quinolones have broad-spectrum antiseptic, weaken or alleviate the effect of gastrointestinal tract post-operation inflammatory.The haemostatic medicament such as carbazochrome salicylate, etamsylate has the effect reducing platelet counts in capillary permeability and fragility, promotion impaired blood capillary pipe end retraction hemostasis and increase blood, accelerate blood coagulation.
The invention provides a kind of gastrointestinal tract stapler with medicine sustained and controlled release function, this anastomat can carry out slow release and the controlled release of medicine in the physiological environment (stomach pH1 ~ 3.5, small intestinal pH5 ~ 7, large intestine pH8.3 ~ 8.4) of the different pH of human body, realizes continuing medication.
for the scheme of dealing with problems
The invention provides a kind of gastrointestinal tract stapler, it is characterized in that, comprising:
Anastomosis staple assembly, comprises anastomosis staple;
Base, described base is the flat annular body of hollow, has ringwise main part substantially, and the main part of described base has multiple through hole running through main part from top to bottom, and described through hole coordinates with described anastomosis staple;
Described anastomosis staple assembly and described base are made up of degradation material and medicinal barium sulfate.
According to gastrointestinal tract stapler of the present invention, it is characterized in that, the cross section of the nail bar part of described anastomosis staple is circle, rhombus, triangle, tetragon, polygon or other regular shapes, and described shape of through holes is consistent with the nail bar shape of cross section of described anastomosis staple.
According to gastrointestinal tract stapler of the present invention, it is characterized in that, described anastomosis staple assembly also comprises at least one ring component, and one at least one ring component described is anastomosis staple connecting ring, and described anastomosis staple connecting ring is connected with many described anastomosis staples.
According to gastrointestinal tract stapler of the present invention, it is characterized in that, described anastomosis staple and described lead to the hole site one_to_one corresponding.
According to gastrointestinal tract stapler of the present invention, it is characterized in that, the internal ring of described base body part is provided with intilted annular slope.
According to gastrointestinal tract stapler of the present invention, it is characterized in that, described anastomosis staple nail bar is provided with latch, is provided with the draw-in groove coordinated with described latch in described through hole.
According to gastrointestinal tract stapler of the present invention, it is characterized in that, described anastomosis staple tip is provided with pawl, and described anastomosis staple enters described through hole, and fixes through described base.
According to gastrointestinal tract stapler of the present invention, it is characterized in that, described through hole is a more than row, and each exhausting hole is evenly distributed on the circle of the axle center of the base same diameter that is the center of circle circumferentially.
According to gastrointestinal tract stapler of the present invention, it is characterized in that, described anastomat has freestanding structure, is made up of anastomosis staple and the head of a nail, and anastomosis staple is made up of nail catcher, nail bar, ailhead, structure that the head of a nail has " inverted gun thorn ".
According to gastrointestinal tract stapler of the present invention, it is characterized in that, described degradation material be selected from PGA, polylactide one or both.
According to gastrointestinal tract stapler of the present invention, it is characterized in that, described degradation material is 100:0-70:30 with the ingredients by weight ratio of medicinal barium sulfate; The disintegration time of described anastomat is 1-3 week.
According to gastrointestinal tract stapler of the present invention, it is characterized in that, described degradation material PGA is 95:5 ~ 85:15 with the ingredients by weight ratio of medicinal barium sulfate.
According to gastrointestinal tract stapler of the present invention, it is characterized in that, described degradation material PGA is 90:10 with the ingredients by weight ratio of medicinal barium sulfate.
According to the preparation method of gastrointestinal tract stapler of the present invention, it is characterized in that, described anastomat carries out melting injection moulding with following condition and is prepared from: mold preheating temperature is 35 ~ 65 DEG C, injection temperature is 215 ~ 235 DEG C, the pressure that shoots material is 800 ~ 1200 bar, briquetting pressure remains 500 ~ 900 bar, and the dwell time is 2 ~ 8 seconds.
The present invention also provides a kind of by the method for gastrointestinal tract stapler medicine carrying of the present invention, it is characterized in that, art for coating is adopted by medicine-carried system to be evenly coated on gastrointestinal tract stapler periphery, drying obtains the gastrointestinal tract stapler of medicine carrying, described anastomat is packed, ethane via epoxyethane or irradiation sterilization.
According to method of the present invention, it is characterized in that, described art for coating condition is: preheating 2-5 minute, coating 100-130 minute, dry 3-5 minute; Inlet temperature 30-40 DEG C; Anastomat temperature 30-37 DEG C; Whiff pressure 0.1-0.5MPa; Hydrojet speed: 3-30g/min.
According to method of the present invention, it is characterized in that, described medicine-carried system comprises polyacrylic resin.
According to method of the present invention, it is characterized in that, described medicine-carried system uses the medicine of at least one being selected from sulfonamides, quinolones, carbazochrome salicylate, etamsylate.
the effect of invention
The present invention has following outstanding effect and feature:
1, compared with manual suture, decrease the puncture time of needlework, thus reduce operating difficulty, improve success rate of operation.The postoperative occurrence probability that can reduce the complication such as coelenteron tissue edema, hemorrhage, inflammation.
2, compared with following closely formula anastomat with titanium, the quantity of anastomosis staple is decreased, and without apparatus legacy.
3, with biodegradable anastomosis ring (English name: Biofragmentable anastomosis ring, be called for short BAR) compare, after anastomosis staple and base coincide, tube chamber broken ends of fractured bone nail is fixed between two rings, decrease purse string suture knotting to reinforce, simplify operating procedure.And the laminating of the tube chamber broken ends of fractured bone is more firm, the locking structure that anastomosis staple ailhead and base " inverted gun thorn " are formed has stronger " stitching power ".
The advantage that stitching power is large is, can ensure that the intestinal tube after stitching bears larger colonic pressure, prevents the broken ends of fractured bone intestinal tube two ends just coincide from again disconnecting.Colonic pressure refer to the food that patients after surgery is taken food or gas flow in bowel lumen formed pressure.This pressure is fatal for the broken ends of fractured bone intestinal tube two ends just coincide, and the intestinal tube just coincide also does not grow intact, once anastomotic stoma bears incessantly this pressure, just there is the possibility again disconnected, cause intestinal contents to flow out from breach, pollute abdominal cavity, threaten patients ' lives.
4, design feature:
(1) base ring there is annular slope to guide intestinal, and isolate intestinal tissue and intestinal contents, be beneficial to intestinal tissue growth and repair and intestinal contents passes through anastomat with annular slope.
(2) there is gap in the middle of anastomosis staple connecting ring and base ring, be convenient to intestinal tube and fill.
(3) easy disintegrating becomes broken end.Compared to fragment, broken end is when intestinal excretes, can not to swipe intestinal tissue, the narrow positions of the intestinals such as the corner of ileocecal valve (valve of ileum and caecum), ascending colon and transverse colon, transverse colon and colon descendens corner, descending colon and Sigmoidocolic corner can not be remained in.Get rid of the very long absorption process of absorbable material, in enteric cavity, realize that macromolecular material is first degraded, this process of disintegrate after anastomat, after gastrointestinal tract healing, discharge anastomat disintegrate thing in time, make the dietary normalization of sufferer, as early as possible rehabilitation.
(4) medicinal barium sulfate with developing function is added.In anastomat disintegrating procedue, barium sulfate discharges gradually with disintegrate thing, and the disintegrating procedue of anastomat is obtained by X Imaging Study, realizes the visual control that anastomat disintegrate is discharged.
5, medicine feature:
(1) although medicinal preparation for oral administration absorbs rapidly but not exclusively, is about 30% ~ 40% of dosage usually; Adopt anastomat medicine carrying with strong points, medicine directly acts on operative site, reduces medicine in gastral loss.
(2) reduce the quantity of postoperative oral, the mode such as intravenous injection anti-inflammation drugs, haemostatic medicament, simplify therapeutic process, alleviate the treatment cost of sufferer.Reduce postoperative patient wound infection, hemorrhage equivalent risk.For the healing in early stage of gastrointestinal tissue provides better repairing environment.
6, peplos feature: as the polyacrylic resin of coated fertilizer for the different pH environment of gastrointestinal tract, discharge ingredient gradually, realize slow release and the controlled release of medicine, plays and postoperatively to continue medication, reach effect of anti-inflammation hemostasis.
Accompanying drawing explanation
Fig. 1 is the structural representation of combination type anastomat.Combination type anastomat adopts free-hand firmly closed or apparatus percussion, by anastomosis staple (2) puncture through intestinal tissue, by anastomosis staple connecting ring (4) and base (1), intestinal tissue folder is closed between the two, cause intestinal tissue placenta percreta to the tissue adhesion of placenta percreta, thus reach anastomotic healing.
Fig. 2 is the structural representation of free-standing anastomat.Stand alone type anastomat adopts apparatus percussion, anastomosis staple bar (2.1) and ailhead (2.2) are punctured through far-end intestinal tissue (8) and near-end intestinal tissue (9), by nail catcher (2.3) and the head of a nail (7), intestinal tissue folder is closed between the two, cause intestinal tissue placenta percreta to the tissue adhesion of placenta percreta, thus reach anastomotic healing.
description of reference numerals
1 base, 2 anastomosis staples, 3 nail, 4 anastomosis staple connecting rings, 5 base annular slopes.
2.1 nail bars, 2.2 ailheads, 2.3 nail catchers, 6 inverted gun thorns, 7 containing the head of a nail of " inverted gun thorn ", 8 far-end intestinal tissues, 9 near-end intestinal tissues.
It will be understood to those of skill in the art that anastomat of the present invention presents in clear and simple mode, and need not draw in proportion.Therefore, dimension of picture amplifies to some extent relative to true material object, to help the understanding to embodiments of the present invention.
Detailed description of the invention
As mentioned above, the invention provides a kind of gastrointestinal tract stapler.
Present invention also offers a kind of gastrointestinal tract to coincide method, the method comprises the following steps: 1. prepare anastomat, and 2. anastomat is assemblied in respectively broken ends of fractured bone intestinal tube two ends, 3. stapled anastomosis device, 4. closure procedure wound, completes operation.
In practical situations both, at the end of anastomosis, broken ends of fractured bone intestinal tube two ends are fixed in the gap between two rings by anastomosis staple, if the tissue carrying out coincideing is intestinal tissue, then adopt intestinal tube inverting suture, anastomat is enclosed within the inside of tube chamber.The anastomat that non-degradable material obtains is after the growth of broken ends of fractured bone intestinal tube two ends is intact, and the tissue necrosis be sandwiched in two circumferential weld gaps comes off, and anastomat entirety excretes with feces.The anastomat that degradation material obtains is in the growth course of broken ends of fractured bone intestinal tube two ends, and lose mechanical property gradually, disintegrate in about 1 ~ 3 week becomes broken end to excrete with feces.
If what carry out is that esophagus, blood vessel etc. coincide, because esophagus, blood vessel are smooth, general employing everting suture technology, anastomat is enclosed within the outside of tube chamber, the anastomat that non-degradable material obtains forever will stay in the body as implantation class medical apparatus and instruments, and the anastomat that degradation material obtains will be degraded into CO gradually
2, H
2the small-molecule substances such as O are absorbed by the body, and degradation cycle at least ensures more than 6 months according to the size of tube chamber.
And the invention provides a kind of gastrointestinal tract stapler of disintegratable, disintegration time can be controlled in certain limit, and it disintegrate can become broken powder, eliminates fragment corner angle damage intestinal, remains in the possibility of intestinal corner.And select medical degradable material PGA as primary raw material, then coordinate with medical development agent barium sulfate.PGA is 100:0-70:30 with the ingredients by weight ratio of medicinal barium sulfate, is preferably 95:5-85:15, is preferably 90:10.When described weight ratio is 95:5-85:15, the disintegration time (1-3 week) of anastomat and stitching pulling force (at least 30N) meet gastrointestinal physiological environment more, after ensure that gastrointestinal tract heals completely, anastomat just loses mechanical property, disintegrate becomes broken end to excrete with feces, completes identical mission.
Present invention also offers a kind of preparation method of described anastomat, be characterised in that described anastomat is carrying out melting injection moulding with following condition: mold preheating temperature is 35-65 DEG C, preferred 40-60 DEG C, more preferably 45-55 DEG C; Injection temperature is 215-235 DEG C, preferred 220-230 DEG C; The pressure that shoots material is 800-1200 bar, preferred 900-1100 bar; Briquetting pressure remains 500-900 bar, preferred 650-800 bar; Dwell time is 2-8 second, preferred 3-6 second.
Gastrointestinal tract stapler provided by the invention has anti-inflammation anastalsis, and it is applicable to the medicines such as sulfonamides, quinolones, carbazochrome salicylate, etamsylate.The medicine such as sulfonamides, quinolones has broad-spectrum antiseptic, slackens or alleviate the effect of gastrointestinal tract post-operation inflammatory.The haemostatic medicament such as carbazochrome salicylate, etamsylate has reduction capillary permeability and fragility, promotes that impaired blood capillary pipe end bounces back and stops blooding; And platelet counts in increase blood, accelerate the effect of blood coagulation.Below these medicines are described further.
Sulfa drugs is as sulfapyridine silver, mafenide, sulfasalazine etc.Sulfapyridine silver, mafenide are used for traumatic infection, antibacterial activity is all had to escherichia coli, clostridium tetani, bacillus subtilis, staphylococcus aureus, Hemolytic streptococcus, streptococcus pneumoniae etc., and sulfapyridine silver is except infection control, wound surface drying, incrustation and Promotive union also can be impelled.Sulfasalazine, at distal small bowel and colon, resolves into 5-aminosalicylic acid and sulfapyridine under enteric microorganism effect.After 5-aminosalicylic acid and the complexation of intestinal wall connective tissue, the long period rests in intestinal tissue and plays anti-inflammation and immunosuppressive action, as reduced escherichia coli and clostridium, suppress the synthesis of prostaglandin and the synthesis of other inflammatory mediator leukotrienes simultaneously.
Quinolones is as enoxacin (ENOXACIN), norfloxacin (norfloxacin), ciprofloxacin, ofloxacin (ofloxacin) etc.Antimicrobial spectrum is large, and especially to aerobic gram negative bacilli, comprising Pseudomonas aeruginosa has powerful bactericidal action, also has good antibacterial action to S. aureus L-forms and product enzyme S. aureus L-forms.Good therapeutical effect is had to the gastrointestinal infection caused by Shigella, Salmonella, enterotoxigenic escherichia coli, aeromonas hydrophila, vibrio parahaemolytious etc.
Haemostatic medicament is as carbazochrome salicylate, etamsylate, tranamic acid, rutosids etc.Carbazochrome salicylate, can reduce the permeability of blood capillary, promotes that impaired blood capillary pipe end bounces back and stops blooding.Be mainly used in capillary permeability increase caused by hemorrhage, as hemorrhage in chronic pulmonary, gastrointestinal hemorrhage, epistaxis, spitting of blood etc.Etamsylate, can increase platelet counts in blood, strengthens its aggregation and adhesiveness, promotes the release of blood coagulation substance, to accelerate blood coagulation.Tranamic acid is antifibrinolytic medicine, can make that established blood clot is unlikely to be dissolved and destroy, and reaches that to prevent caused by fibrinolysis strengthens hemorrhage, hemorrhage etc. for upper gastrointestinal hemorrhage, oozing of blood, surgical operation.Rutosids, is mainly used in the capillary hemorrhage disease for the treatment of fragility increase.
Gastrointestinal tract stapler provided by the invention has medicine sustained and controlled release function, and this anastomat can carry out slow release and the controlled release of medicine in the physiological environment (stomach pH1-3.5, small intestinal pH5-7, large intestine pH8.3-8.4) of the different pH of human body, realizes continuing medication.Described anastomat selects pharmaceutic adjuvant-acrylic resin in Pharmacopoeia of People's Republic of China (2010 editions) as coated fertilizer.This acrylic resin is divided into a kind of stomach dissolution type coating material of polyacrylic resin I type, polyacrylic resin Ⅱ type, polyacrylic resin Ⅲ type three kinds of enteric solubility coating materials and polyacrylic resin Ⅳ type.This acrylic resin also has corresponding external product, now the title of domestic and international corresponding product is listed in the following table.
The domestic and international corresponding product of table 1 acrylic resin
Polyacrylic resin Ⅱ type, this product is that methacrylic acid and methyl methacrylate are with 50:50(weight ratio) ratio copolymerization obtain.Polyacrylic resin Ⅲ type, this product is that methacrylic acid and methyl methacrylate are with 35:65(weight ratio) ratio copolymerization obtain.Polyacrylic resin Ⅳ type, this product is the copolymer of dimethylaminoethyl methacrylate and methyl acrylic ester.Can see Chinese Pharmacopoeia (2010 editions) text kind Part II 1247-1248 page.
The invention provides a kind of by the method for described anastomat medicine carrying, adopt art for coating medicine-carried system to be evenly coated on the periphery of anastomat, described art for coating condition is: preheating 2-5 minute, coating 100-130 minute, dry 3-5 minute; Inlet temperature 30-40 DEG C; Anastomat temperature 30-37 DEG C; Whiff pressure 0.1-0.5Mpa; Hydrojet speed: 3-30g/min.Final drying obtains medicine carrying anastomat, is packed by this anastomat, ethane via epoxyethane or irradiation sterilization.
Below, illustrate that embodiment and comparative example are specifically described embodiments of the present invention.But the present invention is not limited to following embodiment.
Prepared by preparation example 1, raw material
PGA prepare: Acetic acid, hydroxy-, bimol. cyclic ester 500g is added in reactor, in reactor, adds 0.005%(part by weight) stannous octoate catalyst.Sealed reaction system, passes into nitrogen protection reaction.Controlling response system temperature is 120 DEG C, reacts 30 hours.Reactant chopping is made the pellet of 1-8mm particle diameter, weigh and obtain pellet 491g, yield 98.2%.By above-mentioned pellet dissolution in hexafluoroisopropanol solution, the intrinsic viscosity recording polymer with Ubbelohde viscometer in 25 DEG C of waters bath with thermostatic control is 3.28dL/g.
Prepared by injection raw material: encapsulate stand-by by PGA 491g.
Prepared by preparation example 2, raw material
Prepared by PGA: according to the method for preparation example 1, except the response time becomes 25 hours, prepare PGA 495g, yield 99%.Its intrinsic viscosity recording polymer according to the method for preparation example 1 is 3.15dL/g.
Prepared by injection raw material: PGA 495g is mixed (ratio 95:5) with medical grade barium sulfate 26g even, encapsulate stand-by.
Prepared by preparation example 3, raw material
Prepared by PGA: according to the method for preparation example 1, except the response time becomes 32 hours, prepare PGA 498g, yield 99.6%.Its intrinsic viscosity recording polymer according to the method for preparation example 1 is 3.33dL/g.
Prepared by injection raw material: PGA 498g is mixed (ratio 90:10) with medical grade barium sulfate 55g even, encapsulate stand-by.
Prepared by preparation example 4, raw material
Prepared by PGA: according to the method for preparation example 1, except response system temperature becomes 125 DEG C, the response time becomes 32 hours, prepares PGA 490g, yield 98%.Its intrinsic viscosity recording polymer according to the method for preparation example 1 is 3.42dL/g.
Prepared by injection raw material: PGA 490g is mixed (ratio 85:15) with medical grade barium sulfate 86g even, encapsulate stand-by.
Prepared by preparation example 5, raw material
Prepared by PGA: according to the method for preparation example 1, except response system temperature becomes 118 DEG C, prepare PGA 496g, yield 99.2%.Its intrinsic viscosity recording polymer according to the method for preparation example 1 is 3.21dL/g.
Prepared by injection raw material: PGA 496g is mixed (ratio 80:20) with medical grade barium sulfate 124g even, encapsulate stand-by.
Prepared by preparation example 6, raw material
Prepared by PGA: according to the method for preparation example 1, except response system temperature becomes 115 DEG C, prepare PGA 495g, yield 99%.Its intrinsic viscosity recording polymer according to the method for preparation example 1 is 3.17dL/g.
Prepared by injection raw material: PGA 495g is mixed (ratio 70:30) with medical grade barium sulfate 212g even, encapsulate stand-by.
Prepared by preparation example 7, raw material
Prepared by PGA: according to the method for preparation example 1, except the response time becomes 34 hours, prepare PGA 498g, yield 99.6%.Its intrinsic viscosity recording polymer according to the method for preparation example 1 is 3.36dL/g.
Prepared by injection raw material: PGA 498g is mixed (ratio 60:40) with medical grade barium sulfate 332g even, encapsulate stand-by.
Prepared by preparation example 8, raw material
Prepared by PGA: according to the method for preparation example 1, except the response time becomes 28 hours, prepare PGA 490g, yield 98%.Its intrinsic viscosity recording polymer according to the method for preparation example 1 is 3.22dL/g.
Prepared by injection raw material: PGA 490g is mixed (ratio 50:50) with medical grade barium sulfate 490g even, encapsulate stand-by.
Below preparation example 9-16.
Prepared by preparation example 9, raw material
Polylactide prepare: lactide 500g is added in reactor, in reactor, adds 0.004%(part by weight) stannous octoate catalyst.Sealed reaction system, passes into argon shield reaction.Controlling response system temperature is 130 DEG C, reacts 24 hours.Reactant chopping is made the pellet of 1-6mm particle diameter, weigh and obtain pellet 493g, yield 98.4%.By above-mentioned pellet dissolution in phenol/sym-tetrachloroethane (2:3/V:V) mixed solution, the intrinsic viscosity recording polymer with Ubbelohde viscometer in 25 DEG C of waters bath with thermostatic control is 3.31dL/g.
Prepared by injection raw material: encapsulate stand-by by polylactide 493g.
Prepared by preparation example 10, raw material
Prepared by polylactide: according to the method for preparation example 9, except the response time becomes 20 hours, prepare polylactide 498g, yield 99.6%.Its intrinsic viscosity recording polymer according to the method for preparation example 9 is 3.26dL/g.
Prepared by injection raw material: polylactide 498g is mixed (ratio 95:5) with medical grade barium sulfate 26.2g even, encapsulate stand-by.
Prepared by preparation example 11, raw material
Prepared by polylactide: according to the method for preparation example 9, except response system temperature becomes 115 DEG C, prepare polylactide 496g, yield 99.2%.Its intrinsic viscosity recording polymer according to the method for preparation example 9 is 3.04dL/g.
Prepared by injection raw material: polylactide 496g is mixed (ratio 90:10) with medical grade barium sulfate 55.1g even, encapsulate stand-by.
Prepared by preparation example 12, raw material
Prepared by polylactide: according to the method for preparation example 9, except response system temperature becomes 120 DEG C, prepare polylactide 490g, yield 98%.Its intrinsic viscosity recording polymer according to the method for preparation example 9 is 3.18dL/g.
Prepared by injection raw material: polylactide 490g is mixed (ratio 85:15) with medical grade barium sulfate 86.4g even, encapsulate stand-by.
Prepared by preparation example 13, raw material
Prepared by polylactide: according to the method for preparation example 9, except the response time becomes 36 hours, prepare polylactide 492g, yield 98.4%.Its intrinsic viscosity recording polymer according to the method for preparation example 9 is 3.42dL/g.
Prepared by injection raw material: polylactide 492g is mixed (ratio 80:20) with medical grade barium sulfate 123g even, encapsulate stand-by.
Prepared by preparation example 14, raw material
Prepared by polylactide: according to the method for preparation example 9, except the response time becomes 28 hours, prepare polylactide 495g, yield 99%.Its intrinsic viscosity recording polymer according to the method for preparation example 9 is 3.37dL/g.
Prepared by injection raw material: polylactide 495g is mixed (ratio 70:30) with medical grade barium sulfate 212.1g even, encapsulate stand-by.
Prepared by preparation example 15, raw material
Prepared by polylactide: according to the method for preparation example 9, except response system temperature becomes 125 DEG C, the response time becomes 20 hours, prepares polylactide 491g, yield 98.2%.Its intrinsic viscosity recording polymer according to the method for preparation example 9 is 3.21dL/g.
Prepared by injection raw material: polylactide 491g is mixed (ratio 60:40) with medical grade barium sulfate 327.3g even, encapsulate stand-by.
Prepared by preparation example 16, raw material
Prepared by polylactide: according to the method for preparation example 9, except response system temperature becomes 115 DEG C, the response time becomes 26 hours, prepares polylactide 497g, yield 99.4%.Its intrinsic viscosity recording polymer according to the method for preparation example 9 is 3.08dL/g.
Prepared by injection raw material: polylactide 497g is mixed (ratio 50:50) with medical grade barium sulfate 497g even, encapsulate stand-by.
(injection mo(u)lding of anastomat)
According to melting Shooting Technique of the present invention, injection mo(u)lding is carried out to the injection raw material of preparation example 1-16.Concrete process conditions are listed in the table below in 2-5.The mould used in injection mo(u)lding meets following requirement: the structure shown in anastomosis apparatus drawings attached 1 that injection mo(u)lding is obtained.
(the stitching tensile test of anastomat)
Test with ergometer.After the base of anastomat and anastomosis staple stitching, do not get loose under 30N External Force Acting.Experimental results is listed in in following table 2-5.
(test of anastomat degradation time)
Acid-base value: anastomat is soaked completely the external phosphate buffered solution (pH7.2 ± 0.1) being placed in 200mL simulation application environment, glass container headspace is tried one's best little and is ensured safety, under temperature 37 DEG C ± 1 DEG C condition, vibration (40 revs/min) in ZWY-211B type electric heating constant temperature shaking table (Shanghai ZHICHENG Anaiytical Instrument Manufacturing Co., Ltd.), takes out the pH that glass container measures solution every day.Experimental results is listed in in following table 2 to 7.
(anastomat degraded Mechanics Performance Testing)
Compression resistance: after having measured the pH of solution according to the method for " test of anastomat degradation time ", takes out anastomat radial direction and applies pressure, the fragment after feel range estimation size degradation.With piezometer test, apply pressure with the speed of 5mm/min.Anastomat soaks 11 days in the external buffer solution of simulation application environment, answers free from flaw after taking-up under radial direction slowly applies 10N pressure, without damaged.Anastomat soaks 21 days in the external buffer solution of simulation application environment.After taking-up, under radial direction slowly applies 5N pressure, palpus disintegrate or inner and outer ring depart from, and there is no sharp corner angle.Experimental results is listed in in following table 2 to 7.
Table 2 injection mo(u)lding is tested
An explanation is done in disintegrate here in his-and-hers watches 2-4, and disintegrate refers to that the anastomat overall structure be made up of PGA or these macromolecular compounds of polylactide is broken, loses a kind of change procedure of mechanical property.Here disintegrate can be understood as the descending change of of macro object, and being different from degraded change, namely PGA or these macromolecular compounds of polylactide resolve into the change procedure of this microcosmic of micromolecular compound.
Table 3 injection mo(u)lding is tested
Because preparation example 7 and preparation example 8 injection moulding can not prepare molding anastomat, so just do not have the test data of the projects such as stitching pulling force, disintegration time, the corresponding test data in form just represents with " // // // ".
As can be seen from above-described embodiment, when PGA (PGA) is 100:0-70:30 with the ingredients by weight ratio of medicinal barium sulfate, molding anastomat can be obtained.Obtained anastomat has higher stitching pulling force (more than 30N) and mechanical property of degrading preferably, especially when the ingredients by weight of PGA and medicinal barium sulfate is than 95:5-70:30, during preferred 95:5-85:15.And obtained anastomat can disintegrate within the short period in 1-3 week.
Table 4 injection mo(u)lding is tested
The melting molding proces s parameters of polylactide (PLA) and barium sulfate mixture: mold preheating temperature is 40-70 DEG C, preferred 55-65 DEG C; Injection temperature is 220-255 DEG C, preferred 230-240 DEG C; The pressure that shoots material is 1000-1400 bar, preferred 1100-1200 bar; Briquetting pressure remains 700-1000 bar, preferred 800-900 bar; Dwell time is 3-6 second, preferred 4-5 second.
Table 5 injection mo(u)lding is tested
Because preparation example 14, preparation example 15 and preparation example 16 injection moulding can not prepare molding anastomat, so just do not have the test data of the projects such as stitching pulling force, disintegration time, the corresponding test data in form just represents with " // // // ".
When polylactide (PLA) and the ingredients by weight ratio of medicinal barium sulfate are 100:0-80:20, molding anastomat can be prepared.Can select polylactide with medicinal barium sulfate ingredients by weight than the anastomat prepared for 90:10-85:15, this anastomat stitching pulling force is greater than 30N, and disintegration time is within 2.5 weeks.But, with select compared with PGA prepares anastomat with medicinal barium sulfate proportioning, the anastomat disintegration time that the batching of polylactide and medicinal barium sulfate prepares longer (2-3.5 week), and degraded all creates a lot of fragment when applying 5N pressure last day, when pressure will be applied to 10N, fragment just likely disintegrate become broken end.By contrast, the proportioning of PGA and medicinal barium sulfate becomes preferred formula.
Table 6 anastomat degradation process acid-base value changes
Anastomat 6 is degraded 7 days in buffer solution, during the 7th day applying pressure, anastomat overall structure starts disintegrate, loses mechanical property, whole anastomat does not possess cradling function, so just without the test of follow-up pH value, the corresponding test data in form just represents with " // // // ".Anastomat 5, anastomat 4, anastomat 3, anastomat 2 are all based on identical reason, just do not carry out follow-up pH test again.When the pH value of buffer solution is down to about 5.5 or more than 5.5, anastomat 1, anastomat 2, anastomat 3, anastomat 4 degrade 11 days time still can bear the pressure of 10N, at this pressure anastomat free from flaw, without damaged.When the pH value of buffer solution is down to about 4.5 or less than 4.5, anastomat 1 is degraded and is fragmentated at 5N ruptures at pressures for 21 days, and fragment is without corner angle.Anastomat 2 degrade 18 days, anastomat 3 degrade 14 days, anastomat 4 degrade 14 days, anastomat 5 degrade 11 days, anastomat 6 degrades and within 7 days, all can not bear the pressure of 5N, anastomat is ground into broken end at this pressure.
Table 7 anastomat degradation process acid-base value changes
Anastomat 13 is degraded 14 days in buffer solution, during the 14th day applying pressure, anastomat overall structure starts disintegrate, loses mechanical property, whole anastomat does not possess cradling function, so just without the test of follow-up pH value, the corresponding test data in form just represents with " // // // ".Anastomat 12, anastomat 11, anastomat 10 are all based on identical reason, just do not carry out follow-up pH test again.When the pH value of buffer solution is down to about 6.0 or more than 6.0, anastomat 9, anastomat 10, anastomat 11, anastomat 12 degrade 11 days time all can bear the pressure of 10N, at this pressure anastomat free from flaw, without damaged.Anastomat 13 is degraded and is occurred crack, breakage in 11 days.When the pH value of buffer solution be down to about 5.0 and lower time, anastomat 9 is degraded still has larger fragment in 24 days under 5N even 10N pressure, and fragment has corner angle; Anastomat 10 is degraded still has larger fragment in 21 days under 5N even 10N pressure, and fragment has corner angle; Anastomat 11 is degraded and is become fractionlet at 5N ruptures at pressures in 18 days, is ground into broken end under 10N pressure; Anastomat 12 is degraded and is become fractionlet at 5N ruptures at pressures in 18 days, under 10N pressure, be ground into broken end; Anastomat 13 is degraded and is ground into broken end at 5N pressure in 14 days.
Preparation example 17: the preparation of polyacrylic resin I type medicine-carried system
The medicine-carried system of coated 200g anastomat (4g/): in a glass container, add Eudragit L30-55(polyacrylic resin I type) 166.7g, triethyl citrate 5.0g, Pulvis Talci 12.5g, water 215.8g, amount to 400g, and silver sulfadiazine 1g and carbazochrome salicylate 1g, micro-heating, abundant dissolving mix homogeneously, lets cool.Adopt ordinary coating pot that drug solution is evenly coated to anastomat periphery, normal-temperature vacuum is dry.
Preparation example 18: the preparation of polyacrylic resin I type medicine-carried system
According to the method for preparation example 17, except medicine replaces with mafenide 1g and etamsylate 1g.
Preparation example 19: the preparation of polyacrylic resin I type medicine-carried system
According to the method for preparation example 17, except medicine replaces with mafenide 1g and rutosids 1g.
Preparation example 20: the preparation of polyacrylic resin I type medicine-carried system
According to the method for preparation example 17, except medicine replaces with sulfasalazine 1g and carbazochrome salicylate 1g.
(the coated anastomat test of polyacrylic resin I type)
Coating process parameters: preheating 2 minutes, coating 130 minutes, dry 5 minutes; Inlet temperature 32 DEG C; Anastomat temperature 30 DEG C; Whiff pressure 0.15Mpa; Hydrojet speed: 3g/min.
Final drying: be placed in tray, is placed in 30 DEG C of baking ovens 2 hours, obtains medicine carrying anastomat.
According to the different pharmaceutical formula of preparation example 17, preparation example 18, preparation example 19, preparation example 20, prepare the anastomat (anastomat 17, anastomat 18, anastomat 19, anastomat 20) of different medicine carrying composition, this anastomat medicine when pH is greater than in the solution system of more than 5.5 starts stripping, can realize enterally continuing medication.This anastomat is packed, ethane via epoxyethane or irradiation sterilization.
Preparation example 21: the preparation of polyacrylic resin Ⅱ type medicine-carried system
The medicine-carried system of coated 1000g anastomat (4g/): in a glass container, add EudragitL100(polyacrylic resin Ⅱ type) 94g, triethyl citrate 10g, Pulvis Talci 20g, 95% ethanol 1400g, amount to 1524g, and enoxacin 5g and carbazochrome salicylate 5g, micro-heating, abundant dissolving mix homogeneously, lets cool.Adopt ordinary coating pot that drug solution is evenly coated to anastomat periphery, normal-temperature vacuum is dry.
Preparation example 22: the preparation of polyacrylic resin Ⅱ type medicine-carried system
According to the method for preparation example 21, except medicine replaces with norfloxacin 5g and etamsylate 5g.
Preparation example 23: the preparation of polyacrylic resin Ⅱ type medicine-carried system
According to the method for preparation example 21, except medicine replaces with ciprofloxacin 5g and tranamic acid 5g.
Preparation example 24: the preparation of polyacrylic resin Ⅱ type medicine-carried system
According to the method for preparation example 21, except medicine replaces with ofloxacin 5g and rutosids 5g.
(the coated anastomat test of polyacrylic resin Ⅱ type)
Coating process parameters: preheating 3 minutes, coating 120 minutes, dry 5 minutes; Inlet temperature 40 DEG C; Anastomat temperature 30 DEG C; Whiff pressure 0.5Mpa; Hydrojet speed: 25g/min.
Final drying: be placed in tray, is placed in 30 DEG C of baking ovens 2 hours, obtains medicine carrying anastomat.
According to the different pharmaceutical formula of preparation example 21, preparation example 22, preparation example 23, preparation example 24, prepare the anastomat (anastomat 21, anastomat 22, anastomat 23, anastomat 24) of different medicine carrying composition, this anastomat medicine when pH is greater than in the solution system of more than 6.0 starts stripping, can realize enterally continuing medication.This anastomat is packed, ethane via epoxyethane or irradiation sterilization.
Preparation example 25: the preparation of polyacrylic resin Ⅲ type medicine-carried system
The medicine-carried system of coated 1000g anastomat (4g/): in a glass container, add EudragitS100(polyacrylic resin Ⅲ type) 34g, dibutyl sebacate 3g, Pulvis Talci 9g, microcrystalline Cellulose 3g, 95% ethanol 571g, amount to 620g, and silver sulfadiazine 5g and tranamic acid 5g, micro-heating, abundant dissolving mix homogeneously, lets cool.Adopt ordinary coating pot that drug solution is evenly coated to anastomat periphery, normal-temperature vacuum is dry.
Preparation example 26: the preparation of polyacrylic resin Ⅲ type medicine-carried system
According to the method for preparation example 25, except medicine replaces with mafenide 5g and etamsylate 5g.
Preparation example 27: the preparation of polyacrylic resin Ⅲ type medicine-carried system
According to the method for preparation example 25, except medicine replaces with mafenide 5g and rutosids 5g.
Preparation example 28: the preparation of polyacrylic resin Ⅲ type medicine-carried system
According to the method for preparation example 25, except medicine replaces with sulfasalazine 5g and carbazochrome salicylate 5g.
(the coated anastomat test of polyacrylic resin Ⅲ type)
Coating process parameters: preheating 4 minutes, coating 130 minutes, dry 3 minutes; Inlet temperature 35 DEG C; Anastomat temperature 30 DEG C; Whiff pressure 0.25Mpa; Hydrojet speed: 5g/min.
Final drying: be placed in tray, is placed in 30 DEG C of baking ovens 2 hours, obtains medicine carrying anastomat.
According to the different pharmaceutical formula of preparation example 25, preparation example 26, preparation example 27, preparation example 28, prepare the anastomat (anastomat 25, anastomat 26, anastomat 27, anastomat 28) of different medicine carrying composition, this anastomat medicine when pH is greater than in the solution system of more than 7.0 starts stripping, can realize continuing medication of small intestinal, greatly enteral.This anastomat is packed, ethane via epoxyethane or irradiation sterilization.
Preparation example 29: the preparation of polyacrylic resin Ⅳ type medicine-carried system
The medicine-carried system of coated 1000g anastomat (4g/): in a glass container, add Eudragit E100(polyacrylic resin Ⅳ type) 20g, sodium lauryl sulphate 2g, stearic acid 3g, magnesium stearate 7g, distilled water 168g, amount to 200g, and enoxacin 5g and carbazochrome salicylate 5g, micro-heating, abundant dissolving mix homogeneously, lets cool.Adopt ordinary coating pot that drug solution is evenly coated to anastomat periphery, normal-temperature vacuum is dry.
Preparation example 30: the preparation of polyacrylic resin Ⅳ type medicine-carried system
According to the method for preparation example 29, except medicine replaces with norfloxacin 5g and etamsylate 5g.
Preparation example 31: the preparation of polyacrylic resin Ⅳ type medicine-carried system
According to the method for preparation example 29, except medicine replaces with ciprofloxacin 5g and tranamic acid 5g.
Preparation example 32: the preparation of polyacrylic resin Ⅳ type medicine-carried system
According to the method for preparation example 29, except medicine replaces with ofloxacin 5g and rutosids 5g.
(the coated anastomat test of polyacrylic resin Ⅳ type)
Coating process parameters: preheating 2 minutes, coating 60 minutes, dry 3 minutes; Inlet temperature 35 DEG C; Anastomat temperature 30 DEG C; Whiff pressure 0.2Mpa; Hydrojet speed: 4g/min.
Final drying: be placed in tray, is placed in 30 DEG C of baking ovens 2 hours, obtains medicine carrying anastomat.
According to the different pharmaceutical formula of preparation example 29, preparation example 30, preparation example 31, preparation example 32, prepare the anastomat (anastomat 29, anastomat 30, anastomat 31, anastomat 32) of different medicine carrying composition, this anastomat medicine when pH is less than in the solution system of 5.0 starts stripping, can realize continuing medication of stomach.This anastomat is packed, ethane via epoxyethane or irradiation sterilization.
Claims (10)
1. a gastrointestinal tract stapler, is characterized in that, comprising:
Anastomosis staple assembly, comprises anastomosis staple;
Base, described base is the flat annular body of hollow, there is ringwise main part substantially, the main part of described base has multiple through hole running through main part from top to bottom, described through hole coordinates with described anastomosis staple, and the internal ring of described base body part is provided with intilted annular slope;
Described anastomosis staple assembly and described base are made up of degradation material and medicinal barium sulfate.
2. gastrointestinal tract stapler according to claim 1, is characterized in that, the cross section of the nail bar part of described anastomosis staple is circular or polygon, and described shape of through holes is consistent with the nail bar shape of cross section of described anastomosis staple.
3. gastrointestinal tract stapler according to claim 1 and 2, it is characterized in that, described anastomosis staple assembly also comprises at least one ring component, one at least one ring component described is anastomosis staple connecting ring, described anastomosis staple connecting ring is connected with many described anastomosis staples, described anastomosis staple and described lead to the hole site one_to_one corresponding.
4. gastrointestinal tract stapler according to claim 1 and 2, is characterized in that, described anastomosis staple nail bar is provided with latch, is provided with the draw-in groove coordinated with described latch in described through hole.
5. gastrointestinal tract stapler according to claim 1 and 2, is characterized in that, described anastomosis staple tip is provided with pawl, and described anastomosis staple enters described through hole, and fixes through described base.
6. gastrointestinal tract stapler according to claim 1 and 2, is characterized in that, described through hole is a more than row, and each exhausting hole is evenly distributed on the circle of the axle center of the base same diameter that is the center of circle circumferentially.
7. gastrointestinal tract stapler according to claim 1 and 2, is characterized in that, described degradation material be selected from PGA, polylactide one or both.
8. gastrointestinal tract stapler according to claim 1 and 2, is characterized in that, described degradation material is 100:0 ~ 70:30 with the ingredients by weight ratio of medicinal barium sulfate, and the disintegration time of described anastomat is 1 ~ 3 week.
9. gastrointestinal tract stapler according to claim 7, is characterized in that, described degradation material PGA is 95:5 ~ 85:15 with the ingredients by weight ratio of medicinal barium sulfate.
10. gastrointestinal tract stapler according to claim 9, is characterized in that, described degradation material PGA is 90:10 with the ingredients by weight ratio of medicinal barium sulfate.
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| CN103610483B (en) * | 2013-11-14 | 2015-10-28 | 西安交通大学 | A kind of degradable magnetic anastomat of medicine carrying |
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| CN107185053A (en) * | 2017-05-22 | 2017-09-22 | 湖北中创医疗用品有限公司 | Controllable stomach anastomosis bracket of a kind of degradation rate and preparation method thereof |
| CN108577916B (en) * | 2018-03-08 | 2020-10-23 | 戴庆涛 | Preparation method of anastomat for gastrointestinal surgery |
| RU2682487C1 (en) * | 2018-04-03 | 2019-03-19 | федеральное государственное бюджетное образовательное учреждение высшего образования "Ульяновский государственный университет" | Method of prevention of bleeding and spreading of metastases |
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| CN112190772B (en) * | 2020-10-12 | 2021-10-29 | 淮阴工学院 | Anastomosis nail with anti-inflammation function and preparation method thereof |
| CN113616304A (en) * | 2021-06-28 | 2021-11-09 | 南京普立蒙医疗科技有限公司 | Absorbable skull lock for fixing bone flap and manufacturing method thereof |
| CN114870098A (en) * | 2022-05-09 | 2022-08-09 | 许昌市中心医院 | Gastrointestinal anastomat and degradable anastomosis material |
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