CN100558318C - Resorbable thin membranes - Google Patents

Abstract

Disclosed absorbable lactide polymer thin film.Described thin film is made by the polyactide absorbable polymer, and it is manufactured into and can be absorbed in the body with certain hour more lentamente, so that alleviate potential side effect.Described thin film made have extremely thin thickness, for example, thickness is the about 0.300mm of about 0.010mm-.Described thin film can form with having higher viscosity characteristics polylactide polymer extruding, can be preformed into to have thicker part, and can preserve in aseptic packaging.

Description

Resorbable thin membranes

Background of invention

1. related application

The application is to be the U. S. application number 10/385 on March 10th, 2003 applying date, 399 part subsequent application, the latter is to be the U. S. application number 09/805,411 in March 12 calendar year 2001 the applying date, present U.S. Patent number 6,531, it is 11 days U.S. Provisional Application of JIUYUE in 2002 number 60/231,800 that 146 subsequent application, this patent require applying date, with the applying date be the priority of the U.S. Provisional Application number 60/196,869 on March 10th, 2000.It is 4 days the U.S. Provisional Application of JIUYUE in 2002 number 60/408,393 and the applying date to be the priority of the U.S. Provisional Application number 60/399/792 on July 31st, 2002 that the application also requires the applying date.More than application is commonly assigned, and the content of all applications is all done this paper reference by special the receipts.

2. invention field

Present invention relates in general to the medical science graft, more particularly, relate to the method for absorbable film and the described film of use.

3. the explanation of correlation technique

The main clinical problem relevant with surgical repair or inflammation disease is the adhesion that the initial period of agglutination occurs after operation or morbidity.Adhesion is to be connected to form relevant symptom with unusual tissue.For example, described connection may weaken body function, produces sterility, stops up other parts of intestinal and gastrointestinal tract (intestinal obstruction), and produce general uncomfortable, pelvic pain for example.Described symptom may life-threatening under some occasion.The modal form of the adhesion that the operation back occurs takes place because of surgical intervention after operation, but, also may adhesion occur because of other processes or incident, as the pelvis inflammatory diseases, and mechanical damage, the existence of radiotherapy and exogenous material.

In order to prevent postoperative intestinal adhesion, various trials had been carried out already.For example, attempted peritoneal lavage already, heparinization solution, the use of Procoagulants, the improvement of surgical technic, as use microscope or laparoscopic surgical techniques, eliminate the Talcum on the surgical glove, use littler stitching thread, and use physical barriers (thin film, gel or solution), purpose is to reduce adhering to of serosa surface.Unfortunately, adopt the said method industry only to obtain very limited success.Various forms of expanding materials, as the thin film and the stickiness intraperitoneal solution that are designed to limit tissue apposition have been obtained limited success equally.Described barrier material can comprise cellulosic barriers, polytetrafluoroethylmaterial material, and dextran solution.

Thin film or film that disclosed the U.S. Patent number 5,795,584 of authorizing Tokahura etc. tissue adhesion or scar tissue reduce, and the U.S. Patent number 6,136,333 of authorizing Cohn etc. has disclosed similar structure.In the patent of Tokahura etc., biological absorbable polymer and suitable carbonic ester copolymerization are made the single layer adhesion barrier of atresia, then as thin film.In the patent of Cohn etc., made the polyalcohol hydrogel that is used for tissue adhesion, and not by using the carbamate chemical product to carry out crosslinked.But these patents all relate to complicated chemical formula and/or reaction, have produced the special construction that is used for the surgical adhesions barrier.Still there are needs to improved thin film.

Summary of the invention

The invention provides improved Resorbable thin membranes, this thin film can be applicable to various operation occasions, for example, is used for postponing or stoping the tissue adhesion, and reduces cicatrix.In addition, polymer of the present invention and copolymer need better simply chemical reaction and prescription.

According to a feature of the present invention, Resorbable thin membranes is provided, it comprises the uniform substantially composition of amorphous polylactides, for example, 70: 30 poly-(L-lactide-be total to-D the L-lactide).

Described amorphous polylactide membrane can be with initial, higher viscosity characteristics extrusion modling, and described viscosity is equal to or greater than about 5.5g/dL.Described initial viscosity characteristics can promote the reliable formation of described thin film, comprises the appearance that minimizing is ruptured or torn such as thin film in extrusion process.After processing and sterilization, the viscosity characteristics of described thin film can reduce usually.According to other aspects of the invention, can use other higher viscosity characteristicses, as be higher than the viscosity characteristics of 4g/dL, so that in described extrusion process, improve the intensity of described amorphous polylactides material.Described pressing method provides the thin film of the molecularly oriented with biasing.

According to another feature of the present invention, thin film with first surface that glazing is sliding substantially and second surface that glazing is sliding substantially is an atresia, and the thickness of measuring between first surface that glazing is sliding substantially, surface and second that glazing is sliding substantially is the about 0.300mm of about 0.01mm-.Described thin film comprises the part that at least one is thicker, and it can constitute at least a portion of described film edge.Therefore, described thin film has the section thickness of variation.

Disclosed any feature or the combination of features of this paper all is included in the scope of the present invention, as long as described feature is included in any such combination, and can be not conflicting, as passing through textbook, this description, and those of ordinary skills' knowledge is understandable that.By following detailed description and claims, can understand other advantages of the present invention and aspect.

Resorbable thin membranes, comprise uniform component, this component comprises polymer, described polymer is after implanting described thin film in the mammalian body at first, can absorb in the mammalian body being less than in time of 24 months, in described thin film, described polymer has the molecularly oriented of biasing, it is at least one axis bias, and have the viscosity characteristics greater than 1g/dL, described thin film has the first slick surface and the second slick surface, and, described thin film is an atresia, and the thickness of the described thin film of measuring between the described first slick surface and the second slick surface is 0.001mm-0.300mm.

Described polymer comprises amorphous polymer.

Described polymer comprises polyactide.

Described polyactide comprises L-lactide and D, the copolymer of L-lactide.

Described polymer comprises the copolymer of lactide and ε caprolactone.

The molecularly oriented of described polymer is to an axis bias.

The molecularly oriented of described polymer is to two axis bias.

Its thickness is 0.010mm-0.100mm.

Its thickness is 0.015mm-0.025mm.

Its thickness is 0.020mm.

Described thin film has glass transformation temperature, and when this thin film was heated to its glass transformation temperature, the thickness of this thin film had increased at least 5 times.

Described thin film has glass transformation temperature, and when this thin film was heated to its glass transformation temperature, the thickness of this thin film had increased at least 10 times.

It is to soak with a kind of additive that is selected from following group: the chemotaxis material that is used to influence cell migration, be used to influence the inhibiting substances of cell migration, be used to influence the mitogenesis somatomedin of cell proliferation, and the somatomedin that is used to influence cell differentiation.

It is installed in the aseptic packaging of sealing.

Also have at least one thick part, the length of the part that each is thick equals or is shorter than the greatest length of described thin film, and width is greater than 0.5mm, and thickness is greater than 2 times of described thin film central thickness.

Described thick part is outstanding from described two slick surfaces, and forms at least a portion of described film edge.

The first thick part has formed at least a portion at first edge of described thin film, and the second thick part has formed at least a portion at second edge of described thin film.

When described thin film was heated to its glass transformation temperature, the thickness of described thin film had increased more than 2 times.

Also comprise a plurality of holes that distribute along described thick part.

Also comprise along a plurality of holes of the marginal distribution of described thin film.

Its viscosity characteristics is greater than 2g/dL.

Its viscosity characteristics is 3g/dL.

It has shrinkage characteristics heterogeneous.

It has the directional retraction characteristic.

Resorbable thin membranes, the uniform component that comprises a kind of polymer, described polymer is squeezed into such thin film: after implanting in the mammalian body first, can absorb in 24 months in the described mammalian body being less than, has viscosity characteristics greater than 1g/dL, and have the first slick surface and the second slick surface, and the thickness of measuring between the first slick surface and the second slick surface is 0.010mm-0.030mm.

Described polymer comprises amorphous polymer.

Also comprise the part that at least one is thick, the length of described at least one thick part equals or is shorter than the greatest length of described thin film, width is greater than 0.5mm, and compares with the thickness at the position except described at least one thick part of described thin film, and its thickness is big 2 times.

Described thick part is outstanding from described two slick surfaces, and forms at least a portion of described film edge.

The first thick part has formed at least a portion at first edge of described thin film, and the second thick part has formed at least a portion at second edge of described thin film.

Described thick part can effectively provide the rigidity of described thin film.

Also comprise a plurality of holes that distribute along described thick part.

Described thin film is an atresia, and comprises polyactide.

Resorbable thin membranes comprises:

The first slick surface and the second slick surface, wherein, the thickness between the first and second slick surfaces is 0.01mm-0.300mm; With

The part that at least one is thick, the length of described at least one thick part equals or is shorter than the greatest length of described thin film, width is greater than 0.5mm, and compare with the thickness at the position except described at least one thick part of described thin film, its thickness is big 2 times, and the viscosity characteristics that has is equivalent to pre-extruding and pre-sterilization viscosity properties greater than 4g/dL.

Described thick part is outstanding from described two slick surfaces, and forms at least a portion of described film edge.

Comprise first edge that forms described thin film at least a portion the first thick part and form the second thick part of at least a portion at second edge of described thin film.

Also comprise a plurality of holes that distribute along described thick part.

Described at least one thick part comprises a plurality of thick parts, and described thin film is made with amorphous polymer.

Described polymer comprises polyactide.

Described polymer comprises L-lactide and D, the copolymer of L-lactide.

Described polymer comprises caprolactone.

Described polymer has the molecularly oriented towards the biasing of an axis.

Described polymer has the molecularly oriented towards the biasing of two axis.

Thickness between the first and second slick surfaces is 0.015mm-0.025mm.

Described thin film has glass transformation temperature, and when described thin film is heated to its glass transformation temperature, at least 5 times of the thickness increases of this thin film.

Described thin film has glass transformation temperature, and when described thin film is heated to its glass transformation temperature, at least 10 times of the thickness increases of this thin film.

Described thin film is that liquid is impermeable.

Also comprise the additive that is immersed in the described thin film, described additive is selected from a kind of in following group: the chemotaxis material that is used to influence cell migration, be used to influence the inhibiting substances of cell migration, being used to influences the mitogenesis somatomedin that cell increases, and the somatomedin that is used to influence cell differentiation.

It is installed in the aseptic packaging of sealing.

Its viscosity characteristics is greater than 1g/dL.

Its viscosity characteristics is greater than 2g/dL.

Description of drawings

Fig. 1 a represents thin film, and wherein, the molecularly oriented of amorphous polylactides is at an axis upper offset;

Fig. 1 b represents thin film, and wherein, the molecularly oriented of described amorphous polylactides is to two axis bias;

Fig. 2 a represents to have the thin film of thick part;

Fig. 2 b represents to have the thin film of thick part, and this thick part has constituted the part of described film edge;

Fig. 2 c represents to have the thin film of thick part, and this thick part has constituted the edge of described thin film;

Fig. 2 d and 2e are illustrated in the thin film that has part thick more than above it.

Fig. 2 f represents to have the thin film of thick part with holes;

Fig. 3 a represents the laminotomy process, wherein, and the part that vertebra cantle (thin layer) taken out in operation;

Fig. 3 b is the enlarged diagram of Fig. 3 a;

Fig. 3 c represents according to the thin film on the terminal point nerve root that is applied in notochord of first kind of preformed embodiment of the present invention;

Fig. 4 represents according to the thin film on two terminal point nerve rooies that are applied to described notochord of second kind of preformed embodiment of the present invention; With

Fig. 5 represents according to the thin film on four terminal point nerve rooies that are applied to notochord of the third preformed embodiment of the present invention.

The explanation of the preferred embodiment of the invention

Below in detail referring to the preferred embodiments of the invention, the example of these embodiments shown in the drawings.As possible, same or analogous Reference numeral is used for drawing and description, so that represent same or analogous parts.Should be pointed out that accompanying drawing is a reduced form, and do not become accurate ratio.About the description of this paper, only be for convenience and clear, the direction title, as the top, bottom, left side, the right side, upwards, downwards, the top, above, below, under, the back is that relative accompanying drawing uses with the front, these direction nouns should be understood as and limit scope of the present invention by any way.

Although the description of this paper is represented some illustrative embodiment, should be understood that these embodiments provide with the form of giving an example, rather than provide with finite form.Although typical embodiments has been discussed, being intended that of below describing in detail is understood as that and comprises and contained all improvement, substitute, and evolutionary approach, these schemes belong to design of the present invention and the scope that appended claims limits.

According to the Resorbable thin membranes of a kind of embodiment of the present invention, comprise the uniform substantially component that contains polyactide.In illustrated embodiment, described polyactide is molecularly oriented amorphism and/or that have deflection.In this article, amorphous polylactides is that those can not produce the material of X-ray diffractogram clearly.This polymer may comprise that seldom (if any) construction unit is with the tactic zone of three-dimensional regular (crystallization); And their structure may present with the chaotic form of long molecule, wherein, may exist parallel substantially, but the group of orderly inadequately chain part.In one embodiment, it is amorphous that phrase " amorphous substantially " can replace term in this article, and in another embodiment, it is amorphous that phrase " amorphous in a way " or " amorphous slightly " can replace term in this article.

Barrier film of the present invention can be with various biodegradable materials, as absorbable polymer.According to a kind of embodiment of the present invention, the indefiniteness polymer that can be used for producing barrier film of the present invention comprises lactide (L, D, DL, or their combination), Acetic acid, hydroxy-, bimol. cyclic ester, the trimethylene carbonic ester, the polymer of caprolactone (for example, copolymer) and/or their physics and chemical combination.In one embodiment, described barrier film comprises polyactide, and they can be L-lactide and D, the copolymer of L-lactide.For example, described copolymer can comprise the L-lactide of about 60-80% and the D of about 20-40%, the L-lactide, and in preferred embodiments, described copolymer comprises 70: 30 poly-(L-lactide-be total to-D the L-lactide).In one embodiment, described barrier film is by coming from one or more cyclic esters, and as lactide (that is, L, D, DL, or their combination), the polymer of 6-caprolactone and Acetic acid, hydroxy-, bimol. cyclic ester (for example, homopolymer and/or copolymer) is made.For example, in one embodiment, described barrier film can comprise about 1-99% 6-caprolactone, or in another embodiment, can comprise the 20-40% 6-caprolactone.In a kind of example, barrier film comprises 65: 35 poly-(L-lactide-be total to-6-caprolactone).In other embodiments, butyrolactone, valerolactone, or the dimethyl propylene lactone can use or is used to replace 6-caprolactone with 6-caprolactone.In another embodiment, described barrier film can comprise copolymer, and this copolymer comprises lactide and Acetic acid, hydroxy-, bimol. cyclic ester, and it can absorb in the body quickly than above-mentioned poly-(L-lactide-be total to-D the L-lactide).

In this preferred embodiment, described thin film can be used pressing method production, for example, and method known in the field.Described pressing method is preferred for effectively producing described thin film.In addition, the thin film by this extrusion technique production may not have the residual of solvent in thin film, and, molecular bias can also be provided, comprise predetermined molecular bias.In a preferred embodiment of the invention, the single shaft extruding can be used to produce thin film of the present invention.In improving embodiment, the twin shaft pressing method can be used to produce described thin film.In one embodiment, can push the combination mixture that contains the amorphism absorbable polymer, so that produce thin film of the present invention, as the amorphism lactide polymer, for example, it can be poly-L-lactide or more preferably poly-(L-lactide-be total to-D the L-lactide).In one embodiment, poly-(L-lactide-altogether-D, L-lactide) 70: 30Resomer LR708 (produced and provided by the Boehringer Ingelheim KG of Germany) pushes, so that produce thin film of the present invention.

According to an aspect of the present invention, described thin film has the viscosity characteristics of particular range.In this article, " viscosity characteristics " is the viscosity index of polymer dilute solution, and the natural logrithm that is expressed as relative viscosity is the ratio of the concentration of unit with weight in grams with per 100 milliliters of solvent polymeric things.Those skilled in the art can be interpreted as viscosity characteristics the intrinsic viscosity as in this area being the solution used always.In one embodiment, thin film of the present invention has molecular bias, shows that they are produced by extrusion technique, and has higher viscosity characteristics.

According to an aspect of the present invention, discovery can be pushed the amorphous polylactides compositions of pre-extruding viscosity characteristics greater than about 5g/dL, so that produce thin thin film of the present invention.According to other aspects of the invention, can use other higher viscosity characteristicses, as surpassing the viscosity characteristics of 4g/dL, so that improve intensity at amorphous polylactides material described in the process of extrusion process.

Initial high (promptly pre-extruding) viscosity characteristics of described amorphous polylactides has the reliable molding that is beneficial to described thin film, for example, is included in the weakening that reduces described thin film in the described extrusion process, the appearance of rupturing or tearing.Although after processing and sterilization, the viscosity characteristics of described thin film is lower, the initial higher viscosity characteristics of described thin film has the low thickness to the part millimeter of the extruding of being beneficial to.For example, have found that, initial (pre-extruding) viscosity characteristics amorphous polylactides extruded polymer in being approximately the about 7g/dL scope of 5g/dL-can be become thickness is the thin film of about 0.02mm, and the viscosity characteristics that obtains is approximately the about 3.5g/dL of 2.5g/dL-, has adopted the disinfection technology that can significantly not change the viscosity characteristics of described material simultaneously.In one embodiment, ethylene oxide,1,2-epoxyethane is used for to described thin film sterilization.It is believed that ethylene oxide,1,2-epoxyethane can not cause significantly the weakening of viscosity characteristics of described thin film.In other embodiments of using such as other disinfection technologies of electron beam, resulting viscosity characteristics may be about 1.75 for about 1.25g/dL-, rather than the about about 3.5g/dL of 2.5g/dL-.In such as other embodiments of use electron beam disinfectant, the viscosity characteristics of the thin film of extruding is greater than about 1g/dL.In one embodiment, the viscosity characteristics of described thin film is greater than about 2g/dL.Preferably, the viscosity characteristics of thin film of the present invention is approximately the about 3.5g/dL of 2.7g/dL-.

According to an aspect of the present invention, the molecularly oriented of described amorphous polylactides is setovered.Above-mentioned extrusion process can provide the molecularly oriented of this biasing.The molecularly oriented of described biasing can be scheduled to, so that suitable technology can be used to produce the disclosed thin film of this paper as suitable extrusion process.In one embodiment, the polymer chain of described thin film is arranged along an axis substantially, as shown in Figure 1a.For example, it is about 65% that the fragment of described polymer chain or polymer chain surpasses, and preferably surpassing about 80% is to arrange along the axis 101 of thin film 100.

In one embodiment, described polymer chain is arranged along two axis substantially.Fig. 1 b represents to have the thin film 102 of the first axle 103 and second axis 104.Described polymer is arranged along described axis.In this embodiment, it is about 50% that the fragment of described polymer chain or polymer chain surpasses, and preferably surpasses approximately 90%, arranges along one of these two axis substantially.In one embodiment, the polymer of described arrangement is an equal proportion between the first axle 103 and second axis 104.In another embodiment, the polymer that is arranged on the first axle 103 is more than the polymer that is arranged on second axis 104.For example, about 45% polymer is arranged on the first axle, and 55% polymer is arranged in second axis.In one embodiment, described axis has constituted the angle 106 that is lower than 80 degree.Preferably, described axis constituted be lower than about 45 the degree, more preferably less than 30 the degree, more preferably less than 20 the degree angles 106.

The molecularly oriented of described amorphous polylactides can give described thin film various physical characteristics.For example, when described thin film being enough to described thin film is heated to its heat treatment of glass transformation temperature, the thin film with molecularly oriented of biasing may shrink along the direction perpendicular to axis substantially.As shown in Figure 1a, when the thin film 100 of the molecularly oriented with biasing was accepted heat treatment, the direction of contraction 105 may be substantially perpendicular to axis 101.In addition, when described thin film was heated, the molecularly oriented of described deflection allowed the direction of shrinking is controlled or optionally control.Need under the occasion of special construction and size when implanting described thin film, this feature may be favourable.

In one embodiment, in extrusion process, by having the hole output film of first thickness, then, to second thickness, wherein, first thickness is greater than second thickness with described film stretching.First thickness may be bigger two times than second thickness, and is more preferably big five times than second thickness.More preferably than big ten times of second thickness.Therefore, will handle subsequently be heated to its glass transformation temperature with the disinfectant thin film time, its thickness will maybe may return to first thickness.

In one embodiment, thin film of the present invention can not shrink equably along all directions when accepting heat treatment.Preferably, when described thin film was heated to glass transformation temperature, thin film of the present invention obviously shrank along the direction perpendicular to described molecular orientation axis, and can obviously not shrink along the direction that is parallel to described molecular orientation axis.For example, thin film of the present invention can be about 30% along shrink about 5%-perpendicular to the direction of described molecular orientation axis, and can shrink about 1%-about 5% along being parallel to molecular orientation axis.In a kind of example, when subsequently described processing and the thin film handled being heated to its glass transformation temperature, its can be along substantially perpendicular to described arrangement axis (for example 101) or some axis (for example 103,104) direction is shunk, and amount of contraction is directly proportional with amount of tension in initial extrusion process.As what present embodiment embodied, along can last till perpendicular to the contraction of described arrangement axis direction always described thin film from second caliper recovery to first thickness.

Thin film of the present invention can have at least one slick substantially surface.Preferably, thin film of the present invention has two (opposite) slick substantially surface.The thickness of the thin film of measuring between described opposite surfaces of the present invention is the about 0.3mm of about 0.01mm-, more preferably about about 0.1mm of 0.01mm-.In preferred embodiments, the thickness of thin film of the present invention is the about 0.025mm of about 0.015mm-.In another kind of preferred embodiment, the thickness of thin film of the present invention is about 0.02mm.

Thin film of the present invention can also comprise at least one at least one the outstanding thick part from described two slick substantially surfaces.In preferred embodiments, described at least one thick part is outstanding from described two slick substantially surfaces.In other words, described thin film can comprise a plurality of positions or the part with different-thickness.In one embodiment, described thin film comprises the first with first thickness and has the second portion of second thickness that wherein, first thickness is greater than second thickness.First may be positioned at the place away from described film edge, or first may be positioned at the edge of described thin film.In addition, first has the length that is no more than described thin film or the length of width.In certain embodiments, described length is less than the length and the width of described thin film.

The delivery outlet of described pressurizing unit can have the shape suitable with the cross section of described thin film.For example, in order to produce two thin film that opposed edges has thicker part at described thin film, the delivery outlet of described pressurizing unit can comprise the orthogonal shape that is substantially with width and height, wherein, the height of described shape by described delivery outlet changes at the opposed edges of the described delivery outlet height greater than the position between two opposite edges of this delivery outlet.In this structure, the profile that is distributed in the height on the described delivery outlet width substantially be distributed in described thin-film width on the profile of thickness consistent.In other embodiments, for example, the thin film that has thick part on its opposed edges can use the extrusion device with rectangle delivery outlet.In other embodiments, described thick part can form by the mode such as machining, and described machining can be carried out separately, perhaps carries out with extrusion process combination discussed above.Except above-mentioned technology, this technology can be arranged by the manufacture order axial element, wherein, for example, about 80% or above thin film molecules align along a direction, can also produce the thin film of twin shaft by using, wherein, pressure-air be blowed in the tubular film of exporting by described circular delivery outlet such as circular delivery outlet to molecularly oriented.

Preferably, described thick part can effectively provide the combined function with described thin film.In improved embodiment, described thick part can effectively provide rigidity at least a portion of described thin film.In one embodiment, the length of the part that each is thick is equal to or less than the length of described thin film, and width is the about 25mm of about 0.5mm-(and width is not more than the width of described thin film in one embodiment), and thickness is than the thickness of described thin film larger about 2-about 10 times.For example, Fig. 2 a represents thick part 115.In this accompanying drawing, the length 113 of described thick part 115 equals the length of thin film 112, and the width of described thick part 111 is less than the width of thin film 114, and the thickness of described thick part 116 is approximately three times of thickness of thin film 117.With regard to the description of this paper, thick part 115 is equivalent to have the first of first thickness, and the remainder of shown thin film 112 is equivalent to have the second portion of second thickness, and described second thickness is less than first thickness.

In one embodiment, the length of described thick part is less than the length of described thin film.For example, Fig. 2 b represents to comprise the thin film 120 of thick part 121.Described thick part 122 length are less than the length of thin film 123.Thick part 122 same width less than thin film 123.In one embodiment, described thick part has formed the part of described film edge, or has formed the whole edge of described thin film.For example, Fig. 2 b has represented to form the thick part of a part at the edge of thin film 124.Fig. 2 c represents to have the edge 130 at four edges 132, and one of them edge is to form by thick part 131.In one embodiment, thin film comprises part thick more than.For example, Fig. 2 d has represented to form the thin film 140 of the first thick part 141 of the part at first edge 143, and the second thick part 142 that has formed the part at second edge 144.

Preferred film of the present invention comprises amorphous polylactides, for example the uniform substantially component of PLLA.In addition, described amorphous polylactides has the molecularly oriented of biasing because of extruding in described thin film.In addition, described thin film comprises the first and second thick parts, and the width of the part that each is thick is approximately the about 25mm of 5mm-, the about 0.070mm of thickness.The thickness of the described thin film of measuring between two surfaces is about 0.02mm.The viscosity characteristics of described thin film is equivalent to greater than the approximately pre-extruding and pre-sterilization viscosity properties of 4g/dL greater than about 2g/dL.Preferably, the viscosity characteristics of thin film of the present invention is equivalent to greater than the approximately pre-extruding and pre-sterilization viscosity properties of 5.5g/dL greater than about 2.75g/dL.Fig. 2 e represents a kind of embodiment of thin film 150, and it has the first thick part 151 that forms first edge 153 and forms the second thick part 152 at second edge 154.In other improved embodiments, can form other thick parts at other edges or the position of thin film 124.For example, can on four respective edges of rectangular film, form four thick parts.

Thin film of the present invention can also comprise a plurality of holes along at least one marginal distribution of described thin film.Preferably, thin film is passed through in these holes.In one embodiment, described edge has the hole that is formed by at least one thick part.For example, Fig. 2 f represents that thin film 160 has the first thick part 161 and the second thick part 162.Described thick part has along the hole of its length direction.For example, described hole has to be beneficial to described thin film is sewed up organizationally.

With regard in conjunction with regard to, comprise being used for described thin film is combined in such as muscular tissue other soft tissues, or the structural various devices of skeleton, and these devices can use being with or without under the situation in hole.But, according to preferred embodiment, described coupling apparatus is implemented on the actual thick part of described thin film, and it not is to be necessary that even now is done.Except stitching thread, also nail can be used for described thin film is connected juxtaspinal muscle.As another kind of example, can described thin film be fixed on the vertebra with absorbable cortex screw or stud.With described thin-film material hand or folding entering in the anatomical crevices, may just be enough under some occasion, fix its position.Also can be with such as fibrin sealant, or the binding agent of absorbable cyanoacrylate adhesive is used for fixing described thin film separately or with above-mentioned connecting device combination.In preferred embodiments, above-mentioned method of attachment is applied to described thick part.

For example, each the thick part on the described thin film can have the width of the about 25mm of about 0.5mm-.In one embodiment, described thick part is approximately the width of the about 25mm of 5-, it can be used to sew up purpose.In another embodiment, the width of described thick part is about 0.5mm, can use it for caking as mentioned below.According to an aspect of the present invention, thick part can caking, as using bipolar electro-cautery device, and ultrasonic bonding, or similarly method directly seals organizationally, (Fig. 3 is a) as the cerebral dura mater of notochord 30 and terminal point nerve root 32.Heat at each position that this device can be used for described thin film except described thick part, for example not thick edge and at the point at middle part, be heated to the glass transformation temperature that is higher than described thin film at least, and, preferably be higher than its softening point temperature.For example, the glass transformation temperature of PLLA is about 55 ℃, and its softening point temperature is higher than 110 ℃, and described material is and near organizing together it heated, so that these two kinds of compositions bonding together at the interface at them.In another embodiment, can cakings or directly are sealed in two vertebras 20 and 22 one or two (Fig. 3 a), or be sealed on muscle or other soft tissues in the thick part of described thin film or other positions.In another embodiment, can cakings or directly are sealed on the itself in the thick part of described thin film or other positions when using, and for example, wherein, at structure periphery, heating self engages with it then with described winding film.In addition, the described thin film of heated sealant to from one's body or systemic technology can with the another kind of associated methods combination that is used to strengthen grappling.For example, can use electro-cautery device with two or more heated sealant points (that is, thermal weld) that described thin-film material is temporary fixed, add stitching thread then, nail or glue are so that fixing described thin film puts in place.

Thin film of the present invention may be more effective than other thin film, because it is non-normal slick and atresia.For example, the shortage of hole plays a part to form barrier, and it does not allow the interaction of described tissue.The imporosity of described thin film and smoothness can reduce the disorder of tissue, and enhancing guides, and reduce cicatrization.In addition, described thin film slick, discontinuous surface has and is beneficial to described cerebral dura mater and local organization by the motion of described position, therefore, has weakened the friction and wear that may induce scar tissue to form.

In this article, term " atresia " expression material is material impervious to water substantially, and, according to preferred embodiment, be fluid impermeable.But, in improvement embodiment of the present invention, can have micropore on the thin film of the present invention to a certain extent (is fluid penetrable, but cell is impermeable), for example, these Kong Buhui significantly destroy the smoothness on described Resorbable thin membranes surface, down to the cicatrix that causes organizing.In the significantly improved embodiment of limited use, can produce and use cell permeable, but the impermeable hole of blood vessel.

As what the present invention embodied, even under the situation that is not heated to glass transformation temperature, a lot of thin film thicknesses also enough form profile.In one embodiment, thin film of the present invention begins to count about 18-and can be absorbed in the described mammalian body in about 24 months from first this thin film being implanted in mammalian body.Described thin film can be applied to multiple surgery purpose; comprise: the surgical repair of orbital floor fracture; the surgical repair of the ear drum membrane thin film of nasal septum and perforation; covering as protectiveness; so that the promotion osteogenesis, the surgical repair of urethral anatomy, and the reparation of urethral stricture; in the corrective procedure of skull fusion of finishing and forearm fracture, prevent synosteosis; alleviate soft tissue fibrosis or bone tissue growth, in interim repair process, as the interim covering of the umbilical hernia that in utero breaks; at tooth and gum edge guide tissue regeneration; tympanum is repaired, and cerebral dura mater covers and neural reparation, the cardiovascular reparation; hernia repair; tendon coincide, temporary joint partition, wound dressing; cicatrix covering, and the covering that splits as abdomen.Thin film of the present invention is specially adapted to prevent to organize undesired ground fibrosis to combine after operation, and this might cause unusual cicatrization, and disturbs normal physiologic function.Under some occasion, described cicatrization may force and/or disturb reinforcement, correct, or other surgical operations.

For example, evidence suggests that glutinous company of epidural is the possible factor that causes the back operative failure.Epidural fibrosis may occur in spinal cord injury or as operation back surgery complication.The intensive cicatrix that forms on cerebral dura mater and peripheral nerve root was described to " laminotomy thin film " in the past already, and had hinted already that the spinal operation that makes subsequently said more difficultly technically.For example, in the laminectomy for decompression process, preferably after laminotomy, thin film of the present invention is inserted between cerebral dura mater sleeve pipe and the juxtaspinal muscular tissue, and distortion easily, so that the bone marrow factor of the thin plate that sealing exposes.It is believed that described thin-film material is placed on as barrier and can reduce cell transfer between juxtaspinal muscular tissue and the epidural space and invade epidural space from the spongy bone blood vessel of the muscle that covers and adjacent exposure.In addition, test showed already that thin film of the present invention can not disturb wound healing in normal late period, meanwhile, can suppress undesirable adhesion and cicatrization.

Compare with the infiltration rate than the thick film implant of same material, the extremely thin structure of described thin film is considered to significantly to accelerate the infiltration rate of described thin film.But, it is believed that described thin film is absorbed in the body too quickly, can cause undesirable decline of local pH levels, therefore cause/increase the weight of, for example, local inflammation, uncomfortable and/or exogenous antibodies reaction.In addition, uneven (for example fragmentation, the fracture of resulting thin film, coarse or agglomerate is surperficial), degraded may cause the tissue turbulence between the described tissue undesirably prematurely, for example, before finishing suitable healing, cause potential tissue inflammation and cicatrization.It is believed that thickness is that about 0.200mm or littler thin film of the present invention can keep its structural intergrity to surpass for 3 weeks before degraded, and more preferably at least 7 time-of-weeks are so that can realize and optimize described anti-cicatrix function.Compare with the thicker thin film of same material, described thin film can be with the speed degraded of accelerating, and on this degree, described thin film can keep its structural intergrity above 6 months before obvious degradation, more preferably at least 1 year, so that realize and optimize described anti-cicatrix function.Therefore, according to the present invention this polyactide on the one hand again the absorbing polymeric thin film be designed to absorb in the body with slower speed.

It is believed that in the operation rear and reduce acidic levels and/or tissue turbulence, and any concurrent inflammation (for example, swelling) is particular importance that this operation is normally carried out for the inductive uncomfortable specific purposes of amelioration of inflammation in spinal operation.For example, it is believed that nervous tissue may be responsive especially to the acidic levels and the inflammation that raise slightly.In typical spinal surgical procedure, for example, laminotomy is taken out the part of described thin-slab structure from patient's vertebra, so that for example, can contact spinal column and/or dish.

Described thin film can provide with rectangular shape, and for example, this orthogonal each bar limit is several centimetres, perhaps cuts and formed special shape, structure and size by the manufacturer before packing and sterilization.In improved embodiment, various known prescriptions and copolymer, for example, polyactide may influence the physical characteristic of described thin film.Thin film of the present invention has enough pliabilities, so that around anatomical structure, but, it may be necessary carrying out some heating for thicker structure in hot bath.In improved embodiment, some polyactide may become harder and more frangible when thickness surpasses 0.25mm, described polyactide can by with other copolymers and/or other monomers, for example, 6-caprolactone forms together and is softened, and for example, can implement to form thin film.In addition, according to a further aspect in the invention, described thin film can comprise the chemotaxis material that is used to influence cell migration, is used to influence the inhibiting substances of cell migration, be used to influence the mitogenesis somatomedin of cell separation and be used for influencing somatomedin at least a of cell differentiation.Described material can be impregnated in the described thin film, but, can also be coated on one or more surfaces of described thin film.In addition, material can with separate unit be contained on the described thin film or in, after inserting described thin film in patient's body, can effectively promote the selectivity of described material to discharge.

Fig. 3 a represents the laminotomy method, wherein, with two vertebras 20 with opened in 22 minutes, and uses screw 24 and bar 26 fixing.Already the part of described thin plate was taken out, on vertebra 22, stayed window 28 (being expressed as dashed rectangle).Fig. 3 b is the enlarged diagram of the window 28 on the thin plate of vertebra 22.Therefore notochord 30 and terminal point nerve root 32 expose.According to the present invention, described thin film is covered on the cerebral dura mater of notochord 30 and terminal point nerve root 32, near terminal point nerve root 32, form cicatrix so that reduce or eliminate the operation back.

Referring to Fig. 3 c, first welded flange 36 and second welded flange 38 on preformed thin film 34, have been formed.These welded flanges can be made thick part, or only have thick part along their edge.In addition, in improved embodiment, form on other edges of the thin film that thick part can be disclosed below, in other parts formation of described thin film, and/or their combination in any.Trunk portion 40 covers on the notochord 30, and component 42 covers on the terminal point nerve root 32.First welded flange 36 is formed by first crack 44 and second crack 46, and second welded flange 38 is formed by first crack 48 and second crack 50.In application, preformed thin film 34 is covered on notochord 30 and the terminal point nerve root 32, then, make first welded flange 36 and second welded flange 38 to small part around the bending of described terminal point nerve root.The circular distal 52 of component 42 be combined in terminal point nerve root 32 apart from the farther part of notochord 30.As what present embodiment embodied, first welded flange 36 and second welded flange are wound onto around the terminal point nerve root 32, and preferably below it (being the back) reel.In preferred embodiments, subsequently first welded flange 36 is welded on second welded flange 38.Preferably described flange is cut into and intactly be wound on the terminal point nerve root 32, and cover each other, first welded flange 36 can be sewn to separately on second welded flange 38, or as heating replenishing of welding step, so that first welded flange 36 is fixed on second welded flange 38.In another embodiment, add thermal weld or sew up and do not use, but described flange is crimped onto (size that depends on nerve root 32) around the terminal point nerve root 32 only partial or completely.When using stitching thread, described preformed thin film 34 can be preformed, and packs with sewing hole 60 optionally.Preferably edge 64 and 66 is combined on the notochord 30 then by adding thermal weld.Formed the 3rd welded flange 72 by two edges 68 and 70.The 4th welded flange 74 is formed by otch 76 and 78, and the 5th welded flange 80 is formed by otch 82 and 84.Described welded flange can be fixed to be similar in conjunction with the form of welded flange 36 and 38 disclosed modes.The welding of heating can also be fixed along other edges of preformed thin film 34 and along its surface.In addition, can form otch on thin film of the present invention, for example, in the embodiment of improving shape, be positioned on terminal 64 and 66, so that for example be suitable for, spinal cord is handled.

Fig. 4 represents according to the present invention two terminal point nerve rooies 32 that are applied to notochord of another kind of preformed embodiment and 98 thin film.Fig. 5 represent according to the present invention another kind of preformed embodiment with the similar thin film of Fig. 4, but be fit to be applied to four terminal point nerve rooies of notochord.For example, the structure of component 100 and the component 42 of Fig. 3 embodiment and class of operation seemingly, and, other components 102 are made can hold terminal point nerve root 98.In Fig. 5, use Reference numeral 100a, 102a, 100b and 102c show like.Can produce other structures that are used to hold the different anatomic structure.For example, structure can be designed to be made into, pyramidal structure for example, so that be combined in around the base component, ledge extends through described thin film central authorities simultaneously.Stitching thread perforation can be arranged on described thin film around on, and can comprise cell and the permeable hole of blood vessel.

According to the present invention, described preformed thin film preforming and sealing in aseptic packaging are so that use for the surgeon subsequently.Because a purpose of thin film of the present invention is to reduce sharp-pointed edge and surface, it is believed that the preforming of described thin film helps to improve, although be the improvement on less degree, the slick and sly degree at described edge, so that alleviate friction, tissue turbulence and inflammation.In other words, the surface of described thin film and any sharp-pointed edge all are believed to slightly degrade because of the airborne moisture of described thin film Long contact time, thereby form slick and sly edge, and this is considered to very minor effect.In addition, before implanting, initial be heated to glass transformation temperature and can both make any sharp-pointed edge further slick and sly what the pre-cut thin film did.In addition, this phenomenon may appear in extremely thin thin film of the present invention especially easily, and, may be subjected to therefore making the preforming of described thin film help keeping its integrity to a greater extent because operate tearing or losing of causing.

Form provided above-mentioned embodiment by way of example already, and the present invention is not limited to these embodiment.Although above explanation is the complete explanation to the preferred embodiment of the invention, can use various changes, improve, and equivalent.In addition, it is evident that, in the scope of described claims, can implement some other improvement.

Claims (50)

1. Resorbable thin membranes, comprise uniform component, this component comprises polymer, described polymer is after implanting described thin film in the mammalian body at first, can absorb in the mammalian body being less than in time of 24 months, in described thin film, described polymer has the molecularly oriented of biasing, it is at least one axis bias, and have the viscosity characteristics greater than 1g/dL, described thin film has the first slick surface and the second slick surface, and, described thin film is an atresia, and the thickness of the described thin film of measuring between the described first slick surface and the second slick surface is 0.001mm-0.300mm.

2. thin film as claimed in claim 1, wherein, described polymer comprises amorphous polymer.

3. thin film as claimed in claim 1, wherein, described polymer comprises polyactide.

4. thin film as claimed in claim 3, wherein, described polyactide comprises L-lactide and D, the copolymer of L-lactide.

5. thin film as claimed in claim 1, wherein, described polymer comprises the copolymer of lactide and ε caprolactone.

6. thin film as claimed in claim 3, wherein, the molecularly oriented of described polymer is to an axis bias.

7. thin film as claimed in claim 3, wherein, the molecularly oriented of described polymer is to two axis bias.

8. thin film as claimed in claim 3, its thickness are 0.010mm-0.100mm.

9. thin film as claimed in claim 3, its thickness are 0.015mm-0.025mm.

10. thin film as claimed in claim 3, its thickness are 0.020mm.

11. thin film as claimed in claim 3, wherein, described thin film has glass transformation temperature, and when this thin film was heated to its glass transformation temperature, the thickness of this thin film had increased at least 5 times.

12. thin film as claimed in claim 3, wherein, described thin film has glass transformation temperature, and when this thin film was heated to its glass transformation temperature, the thickness of this thin film had increased at least 10 times.

13. thin film as claimed in claim 3, it is to soak with a kind of additive that is selected from following group: the chemotaxis material that is used to influence cell migration, be used to influence the inhibiting substances of cell migration, be used to influence the mitogenesis somatomedin of cell proliferation, and the somatomedin that is used to influence cell differentiation.

14. thin film as claimed in claim 3, it is installed in the aseptic packaging of sealing.

15. thin film as claimed in claim 3 also has at least one thick part, the length of the part that each is thick equals or is shorter than the greatest length of described thin film, and width is greater than 0.5mm, and thickness is greater than 2 times of described thin film central thickness.

16. as the thin film of claim 15, wherein, described thick part is outstanding from described two slick surfaces, and forms at least a portion of described film edge.

17. as the thin film of claim 15, wherein, the first thick part has formed at least a portion at first edge of described thin film, and the second thick part has formed at least a portion at second edge of described thin film.

18. as the thin film of claim 15, wherein, when described thin film was heated to its glass transformation temperature, the thickness of described thin film had increased more than 2 times.

19., also comprise a plurality of holes that distribute along described thick part as the thin film of claim 16.

20. thin film as claimed in claim 3 also comprises along a plurality of holes of the marginal distribution of described thin film.

21. thin film as claimed in claim 3, its viscosity characteristics is greater than 2g/dL.

22. thin film as claimed in claim 3, its viscosity characteristics are 3g/dL.

23. thin film as claimed in claim 3, it has shrinkage characteristics heterogeneous.

24. thin film as claimed in claim 3, it has the directional retraction characteristic.

25. Resorbable thin membranes, the uniform component that comprises a kind of polymer, described polymer is squeezed into such thin film: after implanting in the mammalian body first, can absorb in 24 months in the described mammalian body being less than, has viscosity characteristics greater than 1g/dL, and have the first slick surface and the second slick surface, and the thickness of measuring between the first slick surface and the second slick surface is 0.010mm-0.030mm.

26. as the thin film of claim 25, wherein, described polymer comprises amorphous polymer.

27. thin film as claim 25, also comprise the part that at least one is thick, the length of described at least one thick part equals or is shorter than the greatest length of described thin film, width is greater than 0.5mm, and compare with the thickness at the position except described at least one thick part of described thin film, its thickness is big 2 times.

28. as the thin film of claim 27, wherein, described thick part is outstanding from described two slick surfaces, and forms at least a portion of described film edge.

29. as the thin film of claim 27, wherein, the first thick part has formed at least a portion at first edge of described thin film, and the second thick part has formed at least a portion at second edge of described thin film.

30. as the thin film of claim 27, wherein, described thick part can effectively provide the rigidity of described thin film.

31., also comprise a plurality of holes that distribute along described thick part as the thin film of claim 27.

32. as the thin film of claim 25, wherein, described thin film is an atresia, and comprises polyactide.

33. Resorbable thin membranes comprises:

The first slick surface and the second slick surface, wherein, the thickness between the first and second slick surfaces is 0.01mm-0.300mm; With

The part that at least one is thick, the length of described at least one thick part equals or is shorter than the greatest length of described thin film, width is greater than 0.5mm, and compare with the thickness at the position except described at least one thick part of described thin film, its thickness is big 2 times, and the viscosity characteristics that has is equivalent to pre-extruding and pre-sterilization viscosity properties greater than 4g/dL.

34. as the thin film of claim 33, wherein, described thick part is outstanding from described two slick surfaces, and forms at least a portion of described film edge.

35. as the thin film of claim 33, comprise first edge that forms described thin film at least a portion the first thick part and form the second thick part of at least a portion at second edge of described thin film.

36., also comprise a plurality of holes that distribute along described thick part as the thin film of claim 33.

37. as the thin film of claim 33, wherein, described at least one thick part comprises a plurality of thick parts, and described thin film is made with amorphous polymer.

38. as the thin film of claim 37, wherein, described polymer comprises polyactide.

39. as the thin film of claim 38, wherein, described polymer comprises L-lactide and D, the copolymer of L-lactide.

40. as the thin film of claim 37, wherein, described polymer comprises caprolactone.

41. as the thin film of claim 37, wherein, described polymer has the molecularly oriented towards the biasing of an axis.

42. as the thin film of claim 37, wherein, described polymer has the molecularly oriented towards the biasing of two axis.

43. as the thin film of claim 37, the thickness between the first and second slick surfaces is 0.015mm-0.025mm.

44. as the thin film of claim 37, wherein, described thin film has glass transformation temperature, and when described thin film is heated to its glass transformation temperature, at least 5 times of the thickness increases of this thin film.

45. as the thin film of claim 37, wherein, described thin film has glass transformation temperature, and when described thin film is heated to its glass transformation temperature, at least 10 times of the thickness increases of this thin film.

46. as the thin film of claim 37, wherein, described thin film is that liquid is impermeable.

47. thin film as claim 37, also comprise the additive that is immersed in the described thin film, described additive is selected from a kind of in following group: the chemotaxis material that is used to influence cell migration, be used to influence the inhibiting substances of cell migration, being used to influences the mitogenesis somatomedin that cell increases, and the somatomedin that is used to influence cell differentiation.

48. as the thin film of claim 37, it is installed in the aseptic packaging of sealing.

49. as the thin film of claim 37, its viscosity characteristics is greater than 1g/dL.

50. as the thin film of claim 37, its viscosity characteristics is greater than 2g/dL.

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