JP2012024250A - Collagen film and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a collagen film having stretchability so that it can follow the movement of an organ and the like.SOLUTION: The collagen film 10 comprises a first layer 11 having a plurality of collagen fibers 20 disposed along a first direction 21, and a second layer 12 having a plurality of collagen fibers 20 disposed along a second direction 22, the first layer 11 and the second layer 12 being stacked and bonded to each other. The collagen film 10 is heat treated using a hydrophobic solvent. Since the collagen film 10 has stretchability so that it can follow the movement of an organ and the like, the movement of an organ that repeats expansion and contraction, such as the stomach, the intestines, the heart or the lung, will not be hindered and the collagen film 10 will not be ruptured.

Description

  The present invention relates to a collagen membrane in which collagen threads are laminated and a method for producing the collagen membrane.

  2. Description of the Related Art A medical base material using collagen as a material is known as a material used for surgical treatment or treatment of trauma. One of the medical base materials is a collagen membrane. The collagen membrane is formed by arranging a plurality of collagen yarns spun by a wet spinning method in a predetermined direction to form one layer, and another layer in which the collagen yarns are arranged in a direction different from that direction. Are laminated and the layers are bonded to each other (Patent Documents 1 and 2).

JP 2003-301362 A JP 2004-148014 A

  The collagen membrane described above is used as, for example, a medical base material that a tissue regenerates. The collagen membrane is stored in a dry state, and in use, is immersed in physiological saline to be in a wet state having flexibility. Since the collagen membrane has flexibility, it can be fixed to tissues of various shapes.

  However, there is a problem that the collagen membrane lacks stretchability. For example, in an organ that repeatedly expands and contracts, such as the stomach, intestine, heart, and lung, it is desirable that the fixed collagen film expands and contracts following the movement of the organ. If the collagen membrane is not sufficiently expanded or contracted with respect to the movement of the organ, there is a problem that the movement of the organ is hindered or the collagen membrane is broken.

  The present invention has been made in view of the above-described circumstances, and an object of the present invention is to provide a collagen membrane having elasticity that can follow the movement of an organ or the like.

  The collagen membrane according to the present invention includes at least a first layer in which a plurality of collagen threads are arranged along a first direction, and a plurality of collagen threads arranged in a second direction different from the first direction. A collagen film in which the second layer is laminated and the first layer and the second layer are bonded to each other, and is heat-treated with a hydrophobic solvent.

  The hydrophobic solvent is a nonpolar or low polarity solvent, and specifically includes oils and fats and organic solvents. Moreover, oils and fats should just be liquid at heating temperature.

  Further, the method for producing a collagen membrane according to the present invention includes at least a first layer in which a plurality of collagen threads are arranged along the first direction, and a second layer in which the plurality of collagen threads are different from the first direction. A first step of laminating a second layer arranged along the direction, and bonding the first layer and the second layer together to form a thin film; and heating the film with a hydrophobic solvent And a second step.

  The hydrophobic solvent is a nonpolar or low polarity solvent, and specifically includes oils and fats and organic solvents. Moreover, oils and fats should just be liquid at heating temperature.

  According to the present invention, the collagen membrane has elasticity that can follow the movement of the organ and the like, so that the movement of the organ is inhibited in an organ that repeatedly expands and contracts, such as the stomach, intestine, heart, and lung. And the collagen membrane does not break.

FIG. 1 is a schematic diagram showing a collagen membrane 10 according to an embodiment of the present invention. FIG. 2 is an exploded schematic view showing the structure of the collagen membrane 10.

  Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings as appropriate. Each embodiment described below is only an example of the present invention, and it is needless to say that the embodiment of the present invention can be changed as appropriate without departing from the gist of the present invention.

  As shown in FIGS. 1 and 2, the collagen membrane 10 includes a first layer 11 in which a plurality of collagen threads 20 are arranged along a first direction 21, and a plurality of collagen threads 20 in a second direction 22. And the second layer 12 arranged along the first and second layers 12 are laminated and the first layer 11 and the second layer 12 are bonded to each other. The outer shape of the collagen membrane 10 is generally rectangular.

  The collagen yarn 20 is spun using solubilized collagen as a spinning dope. Examples of the method for spinning the collagen yarn 20 from the solubilized collagen solution include the methods described in Patent Documents 1 and 2 described above, JP-A-6-228505, and JP-A-6-228506. It is done.

  The origin of collagen is not particularly limited, but generally examples include cattle, pigs, birds, fish, rabbits, sheep, mice, and humans. Collagen is obtained from the skin, tendon, bone, cartilage, organ, etc. of these animal species by a known extraction method. Further, the type of collagen is not limited to any of the types that can be classified, such as type I, type II, and type III, but type I is preferable from the viewpoint of handling.

  Solubilized collagen is collagen that has been processed to dissolve in a solvent. For example, heat-solubilized collagen, acid-solubilized collagen, alkali-solubilized collagen, enzyme-solubilized collagen, neutral-solubilized collagen Collagen is mentioned. In particular, atelocollagen that has been subjected to a treatment for removing telopeptide, which is an antigenic determinant of collagen, together with solubilization treatment is preferable. Solvents for solubilizing collagen are not particularly limited, but typical examples include dilute acid solutions such as hydrochloric acid, acetic acid, and nitric acid, hydrophilic organic solvents such as ethanol, methanol, and acetone, water, a mixture thereof, water, and the like. Is mentioned. Examples of the method for solubilizing collagen include the methods described in JP-B No. 46-15003, JP-B No. 43-259839, and JP-B No. 43-27513.

  The collagen film 10 is formed by laminating the first layer 11 and the second layer 12 so that the arrangement directions of the collagen threads 20 (first direction 21 and second direction 22) form a predetermined angle. Yes. The predetermined angle is an arbitrary angle other than 0 °, but the acute angle is preferably 20 ° or less, more preferably 10 ° or less, or 70 to 90 °, more preferably 80 to 90 °. 90 °. That the first layer 11 and the second layer 12 are laminated means that the collagen thread 20 constituting the first layer 11 and the collagen thread 20 constituting the second layer 12 are in contact with each other at the boundary. The state that is.

  In the present embodiment, the collagen film 10 is formed by laminating the first layer 11 and the second layer 12, but the third layer is composed of a plurality of collagen threads 20 arranged in a predetermined direction. A fourth layer or the like may be further laminated. In the collagen film 10 in which the third layer, the fourth layer, and the like are laminated, the angle formed by the collagen threads 20 of the layers not in contact with each other is not particularly limited, and may be, for example, 0 °.

  The collagen threads 20 in the first layer 11 are arranged substantially along the first direction 21, but the angle formed by the longitudinal direction of each collagen thread 20 may be slightly deviated from the first direction 21. Specifically, the direction may be shifted by about 0 to 5 ° with respect to the first direction. The angle formed by the longitudinal direction of each collagen thread 20 in the second layer 12 may also be shifted by about 0 to 5 ° with respect to the second direction 22.

  The interval between the plurality of collagen threads 20 in the first layer 11 and the second layer 12 is not particularly limited, but is preferably arranged at an interval of about 0 to 40 millimeters, more preferably about 0. About 10 millimeters, more preferably about 0 to 1 millimeter.

  The collagen film 10 is heat-treated with a hydrophobic solvent in a state where the first layer 11 and the second layer 12 are laminated. The heat treatment with a hydrophobic solvent refers to heating the collagen membrane 10 by immersing it in a hydrophobic solvent heated to a predetermined temperature for a predetermined time. Examples of the hydrophobic solvent include fats and oils and organic solvents. Fats and oils are not particularly limited. For example, vegetable oils such as palm oil, coconut oil, rapeseed oil, soybean oil, corn oil, rice oil, sunflower oil, sesame oil, cottonseed oil, pork fat, beef fat, fish oil, milk fat, etc. Animal fats and oils. Examples of the organic solvent include, but are not limited to, benzyl alcohol, ethylene glycol, propylene glycol, dimethyl sulfoxide (DMSO), dimethylformamide (DMF), and the like. The temperature of the heated hydrophobic solvent is generally preferably about 115 ° C. or higher. The boiling point of the hydrophobic solvent is preferably higher than the heating temperature.

Hereinafter, a method for manufacturing the collagen membrane 10 will be described. The method for manufacturing the collagen membrane 10 is roughly divided into the following two steps.
(1) A first layer 11 in which a plurality of collagen threads 20 are arranged along a first direction 21 and a second layer 12 in which a plurality of collagen threads 20 are arranged along a second direction 22 A first step of laminating and bonding the first layer 11 and the second layer 12 together to form a thin film.
(2) A second step of heating the above-described membrane with a hydrophobic solvent.

  In the first step, as described above, the collagen yarn 20 is spun using the solubilized collagen as a spinning dope. In wet spinning, a collagen solution is usually discharged continuously from a nozzle having a predetermined diameter into a bath filled with a desolvent such as a hydrophilic organic solvent to dehydrate and solidify the collagen solution. Thereby, the collagen thread | yarn 20 in which the collagen solution discharged from the nozzle continued in the shape of a thread | yarn is obtained. The obtained collagen thread 20 is wound up, for example, while rotating a rectangular flat plate-shaped winding member. At this time, an arbitrary first angle 21 or second angle 22 can be set by setting the angle between the long direction of the collagen thread 20 and each side of the rectangular flat plate to be a predetermined angle. For example, after winding the collagen yarn 20 by rotating the winding member while maintaining the first layer 11 at the first angle 21 while maintaining the predetermined angle, the second layer 12 is at the second angle 22. The winding member is changed to a predetermined angle and rotated so that the collagen thread 20 is wound on the first layer 11 and the second layer 12 is laminated.

  By drying the wound collagen thread 20, the collagen thread 20 of the first layer 11 and the collagen thread 20 of the second layer 12 are bonded. Alternatively, the collagen thread 20 wound may be sprayed or impregnated with a collagen solution and then dried to bond the collagen thread 20 of the first layer 11 and the collagen thread 20 of the second layer 12 together. And the rectangular thin flat film | membrane is obtained by cutting off the peripheral part of the rectangular flat plate shape in the collagen thread | yarn 20 wound up by the winding member.

  The film is heat-treated with a hydrophobic solvent. As described above, the heat treatment with the hydrophobic solvent is performed by immersing the film in a hydrophobic solvent heated to about 115 ° C. or more and maintained at a predetermined temperature for a predetermined time. The time for immersing the membrane in the hydrophobic solvent is generally about several seconds. The membrane heat-treated with the hydrophobic solvent is dried to obtain the collagen membrane 10.

  The collagen membrane 10 thus obtained is in a wet state soaked in physiological saline or the like when used. Since the collagen membrane 10 in a wet state has elasticity that can follow the movement of an organ or the like, for example, when the collagen film 10 is fixed to an organ that repeatedly expands and contracts, such as the stomach, intestine, heart, and lung, the movement of the organ And the collagen membrane 10 is not broken.

  Examples of the present invention will be described below.

[Example]
A film was formed by the manufacturing method in the embodiment described above. Specifically, swine-derived type I / III type mixed collagen powder (manufactured by Nippon Ham Co., Ltd.) was dissolved in distilled water for injection (manufactured by Otsuka Pharmaceutical Co., Ltd.) to prepare 7% by weight. Then, the 7 wt% collagen aqueous solution is filled into a syringe (DisposableBarrels / Pistons, 55 mL, manufactured by EFD), and the collagen aqueous solution is mixed with ethanol from the needle (EFD UltraDispensingTips, 27G, ID: φ0.21 mm) attached to the syringe. It discharged in the tank. The discharged 7% by weight collagen aqueous solution was dehydrated in ethanol to form a thread and then pulled up from the ethanol bath. The pulled-up collagen filament was immersed in another ethanol bath completely separated from the ethanol bath at room temperature for about 30 seconds, and further solidified. Subsequently, the collagen filaments pulled up from the second ethanol tank were wound around a plate-like member having a side of 16 cm and a thickness of 8 mm rotating at 15 rpm. In order to evenly wind the collagen thread around the plate member, the plate member was reciprocated at 1.5 mm / second using a reciprocating mechanism that periodically moves the horizontal position of the plate member. Further, when the plate-like member was rotated 365 times, its rotation axis was changed by 90 °, and this was repeated 12 times, and a total of about 4400 times of winding was performed to create a 12-layer laminate of collagen filaments. . This laminate was thermally dehydrated at 130 ° C. under reduced pressure (1 hPa or less) for 24 hours using a vacuum dry oven (EYELA: VOS-300VD type) and an oil rotary vacuum pump (ULVAC: GCD135-XA type). By performing a crosslinking reaction, a total of two collagen non-woven fabrics were created, one on each side of the plate-like member.
Next, swine-derived type I / III type mixed collagen powder (manufactured by Nippon Ham Co., Ltd.) was dissolved in distilled water for injection (manufactured by Otsuka Pharmaceutical Co., Ltd.) to prepare 1 wt%. The collagen aqueous solution prepared to 1% by weight was impregnated into the obtained collagen nonwoven fabric, formed into a film shape, and then sufficiently dried at room temperature. Thereafter, using the vacuum dry oven described above, a thermal dehydration crosslinking reaction was performed at 130 ° C. under reduced pressure (1 hPa or less) for 12 hours to obtain a membranous collagen nonwoven fabric.
This membrane-like collagen nonwoven fabric was immersed in sesame oil heated to 125 ° C. for several seconds and subjected to heat treatment to obtain a collagen membrane.

[Comparative example]
A membrane-like collagen nonwoven fabric was prepared in the same manner as in the above-described examples, and dried without heating with oils and fats to obtain a collagen membrane.

[Tensile test]
Each collagen membrane obtained in Examples and Comparative Examples was dipped in room temperature water for 2 hours to be in a wet state, and cut into strips having a size of 15 mm × 50 mm in length × width to obtain a test piece. Using the strip-shaped long direction as the pulling direction, a tensile tester (manufactured by Shimadzu Corporation: AG-IS) holds the grip so that the distance between each gripping position is 30 mm, and pulls at a speed of 10 mm / min. Went. The force and displacement when the pulling force at that time became maximum, and the force when the test piece broke were measured. The results are shown in Table 1.

  As is clear from Table 1, in the example, the force at the maximum point with respect to the comparative example was reduced, and the displacement was increased. This indicates that the collagen membrane in the example is easier to stretch and has a larger contractible displacement than the collagen membrane in the comparative example. That is, it was confirmed that the collagen membrane in the example was superior in stretchability to the collagen membrane in the comparative example.

10 ... collagen membrane 11 ... first layer 12 ... second layer 20 ... collagen thread 21 ... first direction 22 ... second direction

Claims (4)

  At least a first layer in which a plurality of collagen threads are disposed along a first direction, and a second layer in which the plurality of collagen threads are disposed along a second direction different from the first direction. A collagen membrane, which is laminated and has a first layer and a second layer adhered to each other, and has been heat-treated with a hydrophobic solvent.   The collagen membrane according to claim 1, wherein the hydrophobic solvent is an oil or fat. At least a first layer in which a plurality of collagen threads are arranged along the first direction, and a second layer in which the plurality of collagen threads are arranged along a second direction different from the first direction, A first step of laminating and bonding the first layer and the second layer together to form a thin film;
And a second step of heating the membrane with a hydrophobic solvent. The method for producing a collagen membrane according to claim 3, wherein the hydrophobic solvent is oil.

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