JPS6187563A - medical molded products - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention Field of Application of Industry-1 The present invention relates to medical moldings of Cefnon I polyurethane and/or G: 1 segment poly 1" ruthanurea,
It is used as an artificial blood vessel, a vascular prosthesis, a heart prosthesis, and a human membrane.

Conventional technology Conventional included 1 Yamaguchi! As i, the polyester fiber is knuffed.

- Stretch and tsibrillate a poly-S L7-1 blood vessel with Vl:W 1 and 1-2 and bellows added 1' in a 1-1-1--F shape. (fibrillation), and 1h type artificial blood vessels are used.

In addition, the prosthesis punches are for poly・''/tan i, tx
For ta cloth, felt fabric, Teflon knitted fabric and festival fabric.
Others are used.

Also, the human T pericardium 4J is not used very often, and only a thin Teflon cloth can be used for testing.

The invention has solved the problem, and these existing pipes have a diameter of 11 or limJ and are used without any problems in practical use. ,
In particular, when the length is less than 61 m, the patency results after transplantation suddenly deteriorate, and the diameter of 11 mm, 6 am, l? Person under J 1 curve, especially 4
Curved pipe L of 1 or less
Almost all of them are blocked, and currently 7th grade [Application to practical application A] 11th grade
There are no artificial blood vessels with this diameter.

It is also used in surgery for heart defects and malformations, such as when the middle corner membrane of the heart (the membrane that separates the right atrium and left atrium, or the right ventricle and left ventricle) is missing or has a hole. Surgery for patient's f street and metastasis of human arterial canal (so-called mask-11)
The biogenic properties and the 1
．． ';+:Blood (adding IJ11 to all 1f1, is it necessary to have a moderate elasticity to adapt to the rapid heartbeat?8 and 171 have not yet appeared.

Also, during heart surgery, when the heart covering the heart (pericardial membrane) is removed or surgery is required for resection or resection, it may adhere to the part of the heart because the heart is not attached. 4. There is a strong demand in the field of cardiology for a heartthrob that can serve as a substitute for a heartthrob, which requires a huge amount of time and does not cause problems during surgery.

Means to solve the problemIK Kmentobori l'7 as antithrombotic properties
Rethane has attracted attention as a result of various Ti1) studies. Is there any attempt to use segmented polyurethane molded into a tube or cloth shape as a human face pipe or punch?In the case of 1,000 liters of 6III or more of a small Y, the ψ1 river would be blocked and it would not be practical. Even if a Y-polyurethane film is used in a heart punch, polypartan biotransformation does not occur, and it is thought that it cannot be used for a long period of time.

Inventor υ1, filled with IL1's anti-destructive surface-1, ]1:
Body fitness 1st day' 16
Tan skin/or segmented polyurethane・')I No?
<Hereafter, use Lefmen 1~Bo II I'7 [/ku/', Now and Iro) as li;j 41J l,2, and form '4-/-+ f. 1 concave age r-,'c. '4\Special t' Article 1''1 applied 1-7 porous (-n quality) /
1 structure old 2, 2 minute pores or living cells ['2' resistance 19 u I7i b:';! l'"J" (I do my best)
Stop, to the present invention? There are 11 people (7 people - 1).

The present invention is for 1,000 mufts 1) -9, L; Nari, go;l'1. 5+ or 1000, - 31 membranous #i
-1rl! Q, its concave curve is multiplied by fL 77゛, and its void volume (the total body of the void volume (11 words) is 90%.
This thing is 4Il-i7shi and Zuromonoichi C1 et al. Illusion, its jl+4 construction n. Number 4, l2 Sekumen 1-Poly °
For, 'Non' Herufi machine? Rock drug

- So 1 (, So, 4; t: , i- - 141: Shape and pull = j t)-('71-shaped L)) '('f
1f Kotani ``ζYuUKoshi 2, solidification is all over the place. ko(])jj: ,;'Quantity, I!'I i!l!Mukumen 1 poly・''ru N and/or G111! The state of porosity can be changed by adding a swelling agent of polyurethane and/or segmented polyurethane to a solution of 1/tan 1 urea.

The segmented polyurethane used in the present invention may be a polyester polyurethane or a polyether polyurethane.

Polyester-based polyurethane is produced by combining a polyhydric alcohol such as glycerin or trimethylol, such as ethylene glycol or soylene glycol, and a polyhydric carbonic acid such as adipic acid or dihydric acid. Synthesize a polyester with a terminal hydroxyl group, and combine it with 2.4-)
lylene diisocyanate 1-, diphenyl, methane-4.
4'-diisocyanate, ethylene diisocyanate, and other isocyanate-H-1-containing compounds conventionally used in the production of polyurethane are reacted to produce a prepolymer in which both Song and Rui are isocyanate groups. It may also be prepared by extending the chain using a chain extender.

From the viewpoint of durability in vivo, polyether-based polyurethanes that are superior to hydrolysis resistant 19L are preferred;
l::+-ru, Borip'1 Pirenkuri 2)-ru or your J9 et al.
-L, Boliteto 1 1. ) A prepolymer of J-1/linkinyl and the isocyanate group-containing compound of iii. Preparations 1-7 and 1-1 were obtained by elongating Yti'i with an elongating agent.

In the same ttt'f, relatively lipophilic (freezing water) polyethers volite 1 no meth 1/2/o 1-cyto and 1 hichukai 1' white saiken IF. +Polyurethane containing both of the following: [-Del Boria month Halen autocyto (However-)'Nod1R's carbon number is 2 and/or;l: 3) Polyurethane containing both of ? It is preferable as a poly-1-lyrethane that has both +'1 and mechanical properties.

surface, used in the present invention;! 1.1 "Su・"Rutan aj
When making it, tj”t ”y. ``= lengthening agent J-cyamine, such as ethylene diamine, diethylene diamine, hexII methylene chloride, etc., as a polyurethane urea.Also, chain extender and L-(
It goes without saying that 1) well-known diols such as 11-ester ethylene glycol and -7 tanthiol can be used as the polyurethane;

The most preferred poly(N) recombination) F-11300-3
000 polyethylene glycol: 1-l, polypropylene glycol and /nu L3r polytetramenalene glycol as a soft safety material.

The present invention uses a 7-containing agent (a cyclic ether 1.
It is an organic polar solvent such as 7-mito, trimethyl-r-se-1-ato-1-, and tri-methyl-sulpo-1-), and is used in medical equipment...
From the viewpoint of the reaction, lj, i, the removal of the solvent from the coating film (
It is necessary that it be easy to evaporate (evaporation, washing with water, etc.), and it is desirable that the boiling point be low, with a boiling point of 120°C or less, more preferably a boiling point of 90°C or less. In addition, water-compatible melt 61 is preferable because it can be easily removed by washing with water.

Therefore, preferable cyclic ethers include atotrophuran, soki→Jon, and the like.

In the present invention, (J solvent G, J medium type or mixture thereof can be used.
) coating (l + sen 11) g drug storage or easy, 1j, blindness (u-1)
-Nohi 1 (17 runs and 7; t -1'-'Iin θ paddy 1L
Use the combination 4 and 2.

Porous sense of the present invention / I Bo 111 Lirethane et al. 6
trg! I'll] QW manufacturing method, N and an example (
, (Phil J, Shamata Let 1, -1'JJl+: t
At 7-7, R-casting is immersed in gold-like solidification, and ζ is also 3I.

) U1shi, 1.14 +iii ia! Sefumen 1
- Appropriate solution of 4. 'Soil - menmata (
4 songs); -1,' cast into (immersed in pseudo-solid liquid/IIJ
2"(#), 1. So, soak the 9-shaped manrule (heart 3jn) in the 7-piece polypartan.
1. If you wish to do so, then immerse, pull out, and evaporate the medium. Once the thickness is set to a predetermined value, it may be coagulated by immersing it in a coagulating solution.Alternatively, the ring 4J-suri-notoso 4 is extruded from a flocculent material and treated with a coagulating solution to coagulate it. i;+d can be done in one stage, or in multiple stages, e.g. 4;l: If:r first t.;t: ,l
It may be immersed overnight in a body with a relatively weak coagulation force, and then immersed in a body with a strong coagulation force, for example, water, for a certain period of time to complete the coagulation.

IL + a weak coagulating liquid with pseudo-solidity and U7 (, 91,
It may have the property of swelling segmented polyurethane, etc., and examples thereof include hensyl alcohol, cyclohexyl alcohol, cyclohexanone, methylcyclohexanone, acetophenone, propylene glycol, and ethylene glycol. , camphor, 1-polyamide, phenol, cresol, low molecular weight polyethylene glycol, low molecular weight polypropylene glycol, acetic acid, formic acid, etc.

Coagulation with relatively strong coagulation power? Examples of Il= include water, methanol, ethanol, alcohols with lower alcohol levels such as propatool, and acetone.

In addition, a series of relatively weak coagulating power, such as segment polyurethane, etc., and swelling property, such as segment I, polyurethane, etc.? The present inventors have found that if the segmented polyurethane and the like are mixed in advance within a range in which they are uniformly dissolved, the porosity becomes extremely uniform. Further, the swelling agent does not necessarily have to be a liquid, and may be a salt that dissolves in the solution. For example, calcium chloride, sodium chloride 1", potassium + 1 + ni, 1-1 lium acetate, machinic chloride t2, 1!?... magnesium hydroxide, etc.

This 31, molded product 41 voids 1, 1 poly, 1 poly, 41 voids, 11 holes,
The ratio of the volume of the void to the total volume - 6 Table 1) or 1
9 to 90% (2 is preferable, less than 10% influx proliferation of 7 cells) 1" (Biogenesis, 6)
,, jHL' has little evolutionary effect, and 9 (1) Is it mechanical property that it exceeds 9i?

In order to make a hollow tube, it is necessary to make a hollow tube.
Immediately pour out the liquid (for holes 11, ', etc.) from the annular slit, No. Liquid) is extruded 7; i) The body is placed in L11 solid-liquid. After the hardness is 1!62, roll it around the tube and manufacture it. I'm going to lubricate it again, C.
A solvent or a liquid containing a solvent may be used.

, U. Liquid reading, segmented polyurethane, etc. 11 and 11. /Using a lubricant, the pressed flocculent material is soaked in a coagulating liquid for a short period of 1 (11 minutes).
', 11:1, and core/1M never mix. In addition, if a water mixture containing enough salt to phase separate from the mixture (such as Segment Bo 11 urethane) is used as the core liquid, the salting out effect will result in a relatively smooth hollow inner surface. Get it.

Also, a hollow 11-piece: a rod-shaped cloak with a circular cross section (
It can also be produced by immersing a core metal in a solution such as curved segment polyurethane, pulling it out, repeating this operation as necessary, and dissolving it in a coagulating solution.

The fill J is extruded into the coagulating liquid through a cotton-like slit, and then cast into ■, -[1 appropriate, ', 7).
Then it solidifies? Immersed in the medium (-7, I).

It should be noted that a so-called wet method in which the tube-shaped or sheet-shaped material is directly extruded into 4F solid-liquid may be used, but it is also possible to A wet-dry method of immersion in a coagulating solution may also be used.

It is possible to change the state of the voids in the cross section by appropriately combining the coagulating liquid in the coagulating bath or the core liquid and coagulating liquid.

For example, there are sponge-like voids, agate-like voids, blind-like voids, sponge-like ant-hole-like voids, etc., vacuoles 4J゛ voids, and δ)- (JZl,
-^ or out] 1 (a). 11 of the embodiment of 5 Nio 1 et al., i) O'+ 1 of vacuole 41'. ! ', ,'J ''Ii white 1'1 quality (, slightly inferior or subonpanoi husband horn, 7
1st condition, A person = 1+, ;lJ:, φ, of)”\゛4I
:'s illumination-C is there.

V, coagulation/1 C1'immersion-'l-1'+ii c,:
JJ2's heart? Yo 2 (9, (Sefumen 1 Bo II t't
I. Tan et al.'s Solution Audience 16X J'lr Woman 1+, 51
Ill trfr r
l'il/f marriage: ? 4 Su l! j song ka'l
= Slide 6m A C truck Invention 81, 1: , 1. ^
Out 1-7. , 11. jj the 'F slip-(assumed rI W and )ψi,.

r+1. From molded products from B lp'fne? Completely remove the mixture ((911 crystal) 1ri+? ?')+: l'f+
'4runo, 1, squid, boiling throat'<% ko and d, 1, ((1 complete・FC1′ excluded< (: L-kade・(
(Ru. Chifubu A2) The thickness of Futorno: I',
I), used between 05m++ -2+ui,! l'i':t'Schiff<I:l', (1
, l+111- 1.5++m ,, gjL,
:1 ryo 1p 1. , (i; I', 0.1 open ~
1. Flmm(Yes.+1.(15m++Not/:!i
Let intensity i'iii <, 2 IIm l')
llteL, it's hard to do even one snout.

Medical molding of segmented polyurethane of the present invention + lj
rireikujo, snoring (, knee J and the next, 1, sea urchin.

1,000), -Z-shaped or δ, 1 Sea 14J: Segmented polyurethane and/or: 1-segment polyurethane 1-reare, and a medical molded article having a porous cross section.

2. The medical molded article, wherein the porous aspect of the cross section is sponge-like porous.

3. The above-mentioned medical molded article, wherein the porous state of the cross section described in 1. is a multilayer mesomorph.

4.-F The above-mentioned medical molded article, wherein the porous surface of the analysis surface is in the form of a blind.

5. Medical molded article I-, wherein the porous aspect of the cross section is vacuolar.

6. The medical molded article 1- above, wherein the porous shape of the cross section is an ant hole shape.

7. The medical molded article described above, in which the pore shape in the cross section is larger than the pore shape in the membrane surface.

Action Segment Bolt N) Not only does it make the cross section of the tube-like or film-like shape like L/Tan porous, but it also forms pores that allow mass transfer to both sides of the membrane, and for this reason, it can be used as a vascular prosthesis. Infiltration of living cells from the anastomosis when used as
It begins to proliferate, and either in the blood or on the outer wall. cell infiltration of 4
) Possible, A]: Embedded characteristics t aggravated, anti-thrombotic bullet 11 vascular prosthesis were made.

Example 1 The polyether moiety of sonotosegmen I- is polyester trametene oxy-1 (molecule !fl/1800), which is synthesized using sifrenylmethane-4,4'-isocyan-1-1 and coach-1 noncyamine. The segmented polyurethane lure was melted and a solution was prepared.

Gono? Extrude the liquid from Ring 4J Nisuriso 1 to Shigenobu Dosono (-7, using water as the core liquid ζ, run the extruded flocculent body through a 10 cm space, and once it has passed, introduce it into a water bath and solidify it. Ro, washed with water 1 & rolled up.

Cut the resulting tube into 30cm long pieces and coat with thick film 0.8II.
m tubes were obtained. Microscopic photographs of the cross section and inner surface are shown below. Average of 0.31111 vacuoles 1; - voids and anthole-like pores are found on the inner surface. This porosity is 32%
One person, two people.

Example 2 Polyurethane 4 molecules ii I 3 G O volite 1
Ramethylene glycol, diphenylmethane-4,4'-
Cefmen 1/Kun was used, which was obtained by chain-extending a prepolymer with isocyanate at both ends obtained from diisocyanate using butanediol.

This polyurethane was dissolved in a mixed solvent (mixing ratio 2:1) of TetrahyF Rofuranushi' Kizan, and
After casting, it was submerged in water to solidify. The thickness of the obtained sheet material was 0.6 ma. A cross section of this film is shown in FIG.

The film had vacuole-like voids and nubonge-like voids. The porosity was 42%.

Example 3 8 parts of a prepolymer made from polytetramethylene glycol (7 - 1800) and diphenylmethane-4,4'-Shiisonane-1 and polyethylene glycol (molecules 'l l 200) and diphenylmethane-4
.

Dissolve this 4'2 in dimethylacetate and 20!
! 6 (ha sweat ~ profuse, this) amount 7 throws, 20% of the total amount
Equivalent to 6 J Rubo 11. -1, a, 1″s, JJII got.

, put the solution through an annular slit [:n press U2 out 2, core liquid (7 in 10 J:]), and use the dry-wet horn method (
The product was spun into a tube (μsO) after being soaked in a bath for 71 hours, hardened to 7 degrees, and then washed with water to form a tube (μsO).

The inner surface and cross section of the chief made by this horn method were trousers-like, and the porosity Let: 31%.

The cross-sectional aspect of the molded article 2 is shown in FIG. 3C.

Fruit 111! ! Example 4 Immediately dripping from the annular slit 1. The rutan solution used was the same as in Example 3, or a mixture of dimethylsulfonate and water (2:I) was used as IUQ&. .

The spinning method was the same as in Example 3.

In this method, the inner surface of the tube was made of spongy material and had an anthole-like through hole (No. 4M). The porosity in this case was 4 [1%].

Example 5 The polyurethaneurea used in Example 1 is the polytetra-1-ramethylene glycol used for synthesis with a molecular weight of 1360.
A polyurethane urea was prepared in the same manner, except that This polyurethane urea is dissolved in dimethylacemylamide, formamide corresponding to 35% of the total amount is added to make a refined solution, which is extruded through a linear slit and passed through a 2 cm space into a saturated solution of soda carbonate. It was then introduced into a water bath to complete coagulation, followed by washing with water and then being rolled up.

The obtained sheet-like film was treated with clean water to remove the solvent and dried.

The cross section of this polyurethane urea sheet is shown in Figure 5, and the film on both sides is thin and has blind-shaped voids in the cross section, the porosity is 76%, and the film thickness is 0.7mm. Ta.

Example 6 During molding, the two volumes of liquid extruded through the slit were directly extruded into a water bath without running through the air, and the molding was performed using a so-called wet method.

I-fold of fj-1~ (, I same U4<zuda;h
4,1: But the inner surface is relatively thick.
) was obtained (FIG. 6, film thickness 1.2+u).

Fruiting and Troublesome 7 In this example, the polyester prepared in Example 3 was pounded out of the circular frino 1 and hollow-spun. 762. Small, 1.1: '), '-Shi Same as Example 3.

In this example, the inner surface and cross section of the C31 chip are multilayered, and the structure (Fig. 7) is 1'-1, 1'1, voids and η'1.
It was 15fi%.

Example 8 A stainless steel round rod was immersed in the polyurethane solution prepared in Example 3, and the steps 1 and 1 were repeated 30 times to melt polyurethane around the round rod. Membrane L
Just put it in the water and let it solidify completely! of;:.

It was coagulated for 16 hours, air-dried for 7 hours, coated with kuribin, and taken from a round rod.

The cross section of this tube has a mucoporous structure as shown in FIG.

Example 9 The 11 liter container of urean produced in Example 5 was cast onto a glass plate, the dirt was immersed in the mixed solution (riformamide), and after 5 minutes, it was taken out and placed in water. ■Completed hard. The cross section of the film was porous as shown in FIG. 9D.

Example 10 Tibouf obtained in Example 1.3.4.7.8 (4■
) were transplanted end-to-end into the femoral artery of a mongrel dog, and when examined for patency 1ψ1 one month later, all were found to be patent.

Example 11 Each of the test pieces of Examples 1 to 9 was taken and examined for mechanical strength, and all were implanted into adult mongrel dogs either face-to-face or as a patch to examine in-vivo deterioration. The results are shown in the table below.

Effects of the Invention By making segment polyurethane urea into a porous structure, in addition to its original moderate elasticity and antithrombotic properties, it also has the ability to proliferate cells such as endothelial cells, making it highly biocompatible. shi, small "1"
As a blood vessel and vascular prosthesis (Improved performance 1 and 7)
I was able to create something.

[Brief explanation of the drawing]

Figures 1 to 9 are cross-sectional photographs showing the porosity of each molded product obtained in Examples 1 to 9 of the present invention, respectively, and the percentage is: 1 All If 'l,Of') is 0 times. Applicant Hiroyoshi Not (month (1)
1゛Order) Procedural Amendment (・U-・0Month, 1939], '; Date 1, Indication of Minor Subjects 1982 Patent Application, No. 209250'・'1ai
oi name Medical article 3, Person making the amendment Relationship with the case The person (1, Address: 4-1-194 Yamamoto-cho Minami, Yao-shi, Osaka Prefecture, Agent address: Name 7, Amendment) Subject: Specification Sergeant 40% (1
), Lines 2109 to 21 of the specification [1 [Figure 1----
It is. 1 is corrected by the following illumination. [Figure 1 is a micrograph IJ of the cross section and inner surface of the hollow linear body (tube) obtained in Example 1;
The figure is a photomicrograph showing the cross-section of the polyurethane sort obtained in Example 2; FIG. 3 is a photomicrograph showing the cross-section of the polyurethane tube obtained in Example 3; FIG. A microscopic photograph of the inner surface of the polyurethane tube obtained in Example 5; FIG. 5 is a microscopic photograph showing interdigital voids in the polyurethane sheet obtained in Example 5; A photomicrograph showing a cross section of a polyurethane sheet; FIG. 7 is a photomicrograph of a mesoche-like cross section of the polyurethane tube obtained in Example 7; FIG. 8 is a cross section of the polyurethane tube obtained in Example 8. A micrograph showing the porosity of Example 9; and FIG.
This is a microscopic photograph showing the cross section of the polyurethane film obtained in . ”-to-

Claims (1)

[Claims] 1. A medical molded product in the form of a tube or sheet made of segmented polyurethane and/or segmented polyurethane urea, characterized in that at least a cross section of the medical molded product is porous.