JPS58104926A - Preparation of polydimethylsiloxane having amino groups at both ends - Google Patents

Abstract

PURPOSE:To obtain the titled composition most suitable for antithrombotic materials having the selective permeability, by polymerizing octamethylcyclotetrasiloxane in the presence of bis(3-aminopropyl)tetramethyldisiloxane having amino groups at both ends. CONSTITUTION:Bis(3-aminopropyl)tetramethyldisiloxane having amino groups at both ends is mixed with octamethylcyclotetrasiloxane, and a strongly basic catalyst, e.g. a solution prepared by dissolving 1.0g KOH dried at 70 deg.C under reduced pressure for 5hr in isopropanol purified by the distillation, and concentrating the solution to 100ml total volume, is added to the resultant mixture to carry out the anionic polymerization at about 135 deg.C for 24hr under stirring and give the aimed polydimethylsiloxane having amino groups at both ends.

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to a method for producing polydimethylsiloxane having an ano group at both ends. A domain structure based on aqueous phase separation develops on the surface of the Pretsuta copolymer membrane, which is composed of chains. In such a polyphasic polymer membrane, selective gas and solute permeation is In particular, boridimethylsiloxane (amorphous, hydrophobic, flexibility) and poly(alpha-alpha)ic acid) (melting, hydrophilic, rigidity) are expected to exhibit excellent functions such as properties. Mu-B block copolymer consisting of [
Here, the poly(α-amino acid) block (1 represents polydimethylsiloxane block) is expected to produce membranes with both excellent gas permeability and antithrombotic properties. When the anhydride is polymerized using an amine as an initiator, carbon dioxide is generated and poly(α-amino acid) K is converted. At this time, if a primary or secondary amine is used as an initiator, the initiator will
Therefore, in order to synthesize the above-mentioned block copolymer, first the first or near-term block copolymer must be It is sufficient to synthesize polydimethylshixane having groups at both ends and polymerize α-adenanoic acid N-carboxylic anhydride using this as an initiator. In this case, the important point is the degree of polymerization of polydimethylsilokinane. The aim is to quantitatively introduce amino groups at both ends while strictly controlling the The present invention was completed by devising a method for efficiently introducing amino groups into both ends of polydimethylsilxane (abbreviated as t-PDM8).In other words, the present invention has excellent selective permeability. P with 11iK aono groups at both ends as a backbone for providing antithrombotic materials
The purpose is to provide an efficient method for synthesizing DMB, and its gist is that in the presence of butterfly, bis(J-7minoprovir)tetramethyldisiloxane having amino groups at both ends, The present invention is described in detail below with reference to Examples.

Example 1 Mixing bis(3-aminopropyl)tetramethyldisiloxane field and octamethylcyclotetrasiloxane,
The strong base catalyst used for anionic polymerization using a strong base catalyst as an initiator was KOH/
*Prepare in advance the isopropanol purified by distillation of OP, and concentrate the entire amount to tootl. Polymerization 13! This reaction was carried out by stirring for a scorching time with r''Q to obtain azuno-terminated i'DM8. Example 1 of 0 reactions in which polymers with different degrees of polymerization (b) can be obtained by adjusting the molar ratio of am with tetramethyldisiloxane as appropriate Tsukibi Nishi (H,!1 (Oll,), 81Me
,-3,OK OMl l
cape? , 4 0. t
j de, 4 0. J?
jy, 6 0,14
1 Degree of polymerization Summer, -Amino group titration calculation value lI! Glue value Calculated value Actual value Assurance 〇 39 0.96 0.90 91/
:10 10 0.01 0. lj
fJ coo iso o, cos
-io.

The actual value of the degree of polymerization of amino-terminated pm measured by vapor pressure osmosis method is that of octamethylcyclotetrasiloxane and bis(
3-7 (minoprovir) The calculated value from the heptadyl chain ratio of tetramethyldishixane) was small, but it was shown that the value can be adjusted by the ratio of the prepared ratio of the two. Furthermore, the weight percent of the terminal amino group nitrogen based on the measured molecular weight is approximately the same as the actual value obtained by elemental analysis.
The amino group content obtained by titrating dichloroic acid with a diquinane solution was almost 100%, indicating that the amino groups were completely introduced into the molecular chain terminals of PDM80 obtained by the above method. 0 Compared to the synthesis method of amino-terminated FI) M8 previously proposed by the inventor Go (Patent Application No. Shojj-9/31), this method has a higher rate of amino group introduction and a shorter reaction time. This method is far superior.

Synthesize using the above method and get the nine-point terminal! 'I) n out of MS
FIG. 1 shows the IR spectrum of θ = θ. One absorption seen in the region of too~/100cm-'' in the spectrum is based on the 8l-o-81 bond, and is 100m-' (D absorption ij B 1-OR.

It is said that the polymerization of octamethylshifttetet2cy4quinane by [01 is slow unless it is at a high temperature of 140°C or higher. ) Polymerization carried out in the coexistence of a compound with a boiling point of A method of adding dimethyl sulfoxide (M@, 110), which is said to accelerate the 7-ion polymerization of kyokunan, was adopted, and 90 octamethylcycutet2siloxane 5OIit and bis(J-A-Sho Nobuzonovir)tetramethyl were added. Disiloxane/1
The mixed solution of No. 14 was stirred at 100°C for 1 hour under a nitrogen atmosphere, and then covered with dry KOH/Oki and a lid. Add 1 to 7
1: Stirred and polymerized at 00℃・Reaction solution was mixed with ether Kl
1, shake well with water, then rinse with water, 00. After drying with ・, the p liquid was dried to solidify, and the resulting polymer was tracked for changes in GAC over time. As a result, 10 minutes after the start of the reaction, Ka bis (
It was found that almost all of the tetramethyldisiloxane was introduced at the ends of the linear polysiloxane, resulting in an equilibrium mixture of octamethylcyclotetrasiloxane and high molecular weight polysiloxane.

? kKIiJ IDX & 1Atic TZ-ca 8, et al. Jlffl L & Tracked changes in average molecular weight and reduced viscosity over time. The results showed that within 1 hour of the start of the reaction, there was a significant increase in the molecular weight and viscosity of the produced polymer, followed by a rapid decrease in molecular weight and viscosity due to depolymerization. Such changes were due to the start of the reaction. After one hour, the temperature gradually deteriorated.J)S/J After more than an hour, no change was observed, and the initial octamethylcyclotetrasiloxane and bis(J-aminoglopyru□1)tetramethyldisiloxane. □'A + -T-k h”1□: 1.10 okay. Oh.□.

Based on the above results, the synthesis of amino-terminated FDMIiO was performed using O6/
~0. Add J-K OR and l-rei・-〇, lJO℃
The amino-terminated PDMjl purified by the above method is best reacted at a similar temperature for 1 hour.
・It is preferable to mix it with OH, repeat decantation, and then dry it before use. As described above, according to the method of the present invention, the ano-terminated IDM8 can be efficiently produced. The adeno-terminated PDM8 obtained in this manner is abbreviated as α-amino acid fan-carboxy anhydride (hereinafter α-adenate) acid MOM. No. represents anhydride-carboxylic anhydride) is copolymerized, and the resulting Pluc copolymer has excellent antithrombotic properties. Next, an example of the production of the Pluc copolymer 〇Manufacturing hook l In this example, FDM8 obtained by the method of Example 1 above was used as the initiator polymer.
α-7 mino#t1AC as 蓼-carbobenzoxy b-lysine Ig (hereinafter referred to as L1))
The block polymerization is carried out using the polymerization solvent methylene chloride (tetrahydrofuran can also be used).
Melt both #! Add (Lye(Z)) fc! 0. When stirring carefully, bubbles quickly appeared from the liquid surface, indicating that decarboxylation was occurring. This was placed in a desiccator at 6 o'clock and polymerized.Then, the solvent methylene chloride was distilled off, the mixture was forged, and when added to ether, a white precipitate appeared. According to the 90XR spectrum, the soluble fraction/@J# and the insoluble fraction are 1, and the ether soluble fraction is mostly I'DM8, with a small amount of poly(α −A-ken)
On the other hand, the ether-insoluble fraction did not consist of the desired block copolymer, but may contain a very small amount of α-aranoic acid homopolymer. cannot be excluded @IR spectra of ether insoluble matter) k Iff (oH,
cj.

(measured by forming a film from a solution onto a KLR plate) as shown in Figure o (
roo, -”) -81-0!is fR angle ra movement K
X & Absorbing Part Meeting 1 15 (/RULM, -1) Absorbing part by urethane 0-0 stretching vibration! (/41 (7eIR-9 amide C=0 (A-kendo l)
Absorbing part due to stretching vibration? (1!ru0em-Rear 2d C-9 (A5d I) Absorption part due to stretching vibration Ah, it is estimated that.

Father-in-law, M. 4 Q~, 11]: 11.1. ,,,? 4 1H ■ -0 Production Example 1 In this example, the initiator polymer was obtained by the method of Example 1 above. DM8 t-use, α
- Using r-benzyl-L-glutamate No. (hereinafter abbreviated as 0Lu(OB) No.) as the amino acid MCI, a test was carried out.

AZ terminal PDM81.1 jl and Gzu (Oj3sg
A)) IQ λII and the polymerization solvent cyclized methylene (tetrahydro7ran can also be used) K#! Add molten gold to the mixture (GAu (OBmA) with a light weight of 0.2 M). Shake carefully. If this happens, bubbles will quickly come out from the liquid surface, causing decarboxylation. This was left for 1 hour in a desiccator to polymerize.

The same operation as described in Preparation Example I produced 1 kJt-
Separate and obtain the ether soluble component O6 and the insoluble component Jl.The majority of the ether WJ soluble component is 6, and a small amount of poly(α-7) acid. The ether-insoluble content consists of the target bootsta copolymer, but we cannot exclude the possibility that it contains a small amount of α-electronoic acid polymer.◎Ether-insoluble content The xR spectrum (measured by forming a film on a USr plate from an on, az solution) is shown in the third HIK. In the figure, the codes of M to D are as follows 4
It shows.

0 (toooa-”) -81-OH, bending angle IIk
Absorption part D (/? J0m-9 ester 0 + wO Absorption part 1 by stretching vibration (/A10 down-ri74 doos, o(yt de I) Absorption part by stretching vibration? (/jlOcm-9 Adendo The structure of the absorption copolymer due to stretching vibration is estimated to be as follows, based on the signal intensity ratio determined by adjustment. ◎ 4 Production example In this example, amino-terminated PDM II obtained by the method of Example 1 above was used as the initiator poly!-, and sarcosine nom. ◎ Amino-terminated PDM8/I and 8ar IOA tl
each. Polymerization solvent methylene chloride (tetrahydrogen W7
(You can also use 8ar Nom) and mix both solutions together (make the concentration of 8ar Nom 0.JM) and shake carefully. When this occurred, bubbles quickly appeared from the liquid surface and decarboxylation was observed to occur. This was left in a desiccator for /J hours to polymerize.The product was separated by the same operation as described in Production Example 1, and the ether soluble content was 0. /l and insoluble matter/JIIt were obtained.

Most of the ether-soluble content is d PDIII, and contains a small amount of poly(α-electro)acid.@ The ether-insoluble content consists of the target block copolymer, but a very small amount of α- Contains amino acid homopoly,
tL'ch! Excluding this possibility, the XR spectrum of the ether-insoluble matter (measured by forming a film on a KBr plate from an O%'4 solution) is shown in Figure 1. The symbols M to D in the figure are Indicates the following・mu(/2!0Bi-1-81-OR,
Absorbing part due to stretching vibration Proverb 0 (trans-'') -81-Oll, Absorbing part D due to bending vibration (/4jJtc*-') Amide C!0
(A construction I) Absorption part due to stretching/stretching The structure of this block copolymer is estimated to be as follows based on the tonicity ratio of the signal determined by MMR column.
.

The degree of polymerization of the α-azanoic acid block is determined by the molar number of α-7 base amino acid NO added to the concentration of the amino-terminated FDMS initiator. determined by the degree ratio. A block copolymer with a degree of polymerization exceeding IDO can be formed from an organic solvent to provide a more transparent and flexible film.When producing a block copolymer, a block copolymer can be used for Kll. - asonoacids, alanine, r-alkyl daltagonic acid, aspj (β-alkyl esters of daltanic acid, glycine, seicin, isotetraicine, norleucine, I-carbobenzoxylysine, r-carboxylic acid) Benzoxyornithine, phenylalanine, 0-benzylserine, and halimonium can be used.One or more of these α-arenic) acids may be used in combination. When the a-type Oα-amino acids are added at the same time, one type of α-amino acid is randomly arranged, resulting in nine blocks, but after the polymerization of one No is completed, the first α-amino acid is added. Then, a block copolymer consisting of a zero-order dimethylsiloxane linkage and an α-aconoacid block, which is arranged in a kind of α-aconoacid block, is obtained. We will explain the case of modifying the four-wheel drive.

The block copolymer synthesized in Production Example/
e(m) push is included. Further, the block copolymer synthesized in Production Example J contains a Gzu (OBmA) block. The side chains of these α-amino acid residues can be induced into heteropolar structures by mild chemical treatments. The reaction equation for excessive food such as kernels is K as follows.

Lys(Z) LyeGtu(
OBIA) By chemical modification of the side chains of the Gjuα-adenanoic acid block, block copolymer films with new properties can be synthesized. Examples of such reactions are described below.

Reaction Example 1 Block copolymer CL7s(''))sr-CD''1)me (Lya('') synthesized according to the method of Production Example 1
91n100~30111 dimethylformamide K
Then, 21 g of J j % HBr/muOOH was added, and the mixture was stirred in a room oven for 1 hour. Concentrate the solution, add ether,
After washing by decantation, the R spectrum of the reaction product (KBr tablet method) is shown in Figure 3. Compared to the XR spectrum before reaction (see first reference), /4
Jr! cs-' urethane bond absorption and 700
cm-” absorption based on the benzene ring is weaker,
Lyeψ) residue tfLy residue □It is thought that the structure of the reaction product is as follows.

Me
u(OBgt))s / I t j
After adding tl and stirring at room temperature for 70 minutes, the precipitated white substance was separated from P, water was added, pT1*K was adjusted with i@HoL, and the mixture was stirred for S minutes. The precipitated hard white substance was thoroughly washed with water, further washed with a7ton, and then dried. The XK spectrum (KBr tablet method) of the reaction product is shown in Figure 6. Compared to the XR spectrum before the reaction (see Figure 3), the absorption of the ester bond of /7 J Ocm-”
The absorption based on benzene jlK at 700 cm-'' almost disappeared, and instead the absorption based on the stretching vibration of the group near J k 00 cyw-' appeared.
It is thought that the Bsgz) residue was converted to the 0t11 residue. The structure of the reaction product is estimated to be as follows.

Me Me o=0 H If it is possible to chemically modify only the surface of the block copolymer membrane, it is possible to apply a thin hydrophilic layer to the surface of a strong hydrophobic membrane. An example of surface modification by a heterogeneous reaction of Reaction Example 3 A block copolymer [G A u (OB m 1311-(DM 13
)I H-[G L u (oggz)] u was deposited as a film from dimethylformamide solution, and dNNa0HjO1
7 and methanol tz.

Immersed vertically in the mixture. The reaction was tracked by taking out the film at regular intervals and measuring the attenuated total reflection (TR) spectrum. Figure 7 shows the ATJt- of the block copolymer film.
◎The middle diagram showing the IR spectrum is the ATB-4fl spectrum after being immersed in the above alkaline bath for 1 hour, but absorption based on the symmetrical stretching vibration of the slate group before the reaction in the upper diagram appears. The superficial structure can be thought of as follows.

8-8 6N111 Next, the membrane was mixed with io-citric acid aqueous solution j0d and methanol I! The membrane was immersed in a mixed solution of rOnl and left at ℃ for -0 minutes.The MUTR-IR spectrum of the membrane in this case is shown in the lower part of Figure 7.In this figure,
Around tym-' and around 1:00-1, there is an absorption □ based on the stretching vibration of the carbon acid OH group.
Absorption based on the stretching vibration of the carboxylic acid 0=0 group appears near /00bi-1. Therefore, the surface structure of the film in this state is considered to be as follows.

Chang.

H Next, we will show the results of measuring the antithrombotic properties of a block copolymer obtained by block copolymerizing α-amino acid No. with amino-terminated FDMS obtained by the method of the present invention. Therefore, the antithrombotic properties of the homopolymer of dimethylsiloxane and the homopoly-q-of α-adenoic acid constituting the block copolymer were determined.
Apply it on the surface of the watch glass, and for the rest, first soak it in dimethylformamide solvent (300 WQ of each sample is soaked in dimethyl formamide). The sample was dried overnight using a vacuum pump and used as a test sample. Furthermore, for comparison, we used a crow plate without any treatment.
2 ◎ The following is the standard of the Kenken Method Company. Adult male (weight approx. tsyu)
Add 9M of JOId's blood from the femoral artery of 9, da, tIR1's ACDfg solution (liquid consisting of citric acid, sodium citrate, and glucose), and add this O,J 511
1 was added to each sample prepared on a watch glass as described above, and 0.01M calcium chloride aqueous solution 0.0
- addition of one to initiate clotting. When each set time is reached, distilled water is added to stop blood clots, the formed blood clot is fixed with formalin, and distilled water is substituted. ◎Remove the wet blood clot with a spatula and sandwich it between tissue paper. The weight of the clot after 73 minutes is taken as 100% when using a 0 glass to absorb and weigh excess water.
The blood orange production rate was compared based on the relative weight of 1.90 Test Example 1 In this example, the anti-blood orange property of the gastrointestinal copolymer of σzu (ogmz) and dimethylsiloxane was tested. The homopolymer of OBmA) shows excellent anti-blood orange properties compared to glass ◎However, these block copolymers have even better anti-blood orange properties than the homopolymer and the polymer.@Blocks with different compositions Among the copolymers, poly[O
It can be seen that the chain length of [Ju(ogsz)] Bubroc which is neither too long nor too short exhibits the best anti-blood filtration properties.Test Example 1 In this example, Ly@(Q and dimethylsiloxane blocks are combined). Polymers were tested for anti-orange properties and homopolymers of dimethylsiloxane and Ly-(Z) showed better antithrombotic properties than glass.However, their block copolymers showed better antithrombotic properties than homopolymers. Even better #
Among the block copolymers with different bO compositions, the chain length of the polyCLysK)) block is neither very long nor short compared to the chain length of the PIM8 block. It can be seen that the block copolymer of the present invention exhibits the best antithrombotic properties as described above because of the crystallinity, hydrophilicity, and rigidity of the ζα-adenanoic acid block. This is thought to be due to the amorphousness, hydrophobicity, and flexibility of the dimethylsiloxane block, which creates a microphase-separated structure and the development of a domain structure.Through selective interaction with blood proteins, this structure It is thought that it controls the activation and promotion of platelet organization. Based on the above-mentioned excellent performance, the Pretsuta copolymer obtained from the product of the present invention is suitable for various medical applications requiring antithrombotic properties. This is a book that can be used for devices and materials such as vascular catheters and extracorporeal blood transport circuits. In addition, due to its excellent oxygen permeability, it is used in various medical devices and materials that require both antithrombotic properties and oxygen permeability, such as gas exchange membranes for oxygenators, membranes for artificial skin, and contact lenses. The above explanations and the nine specific examples of implementation relate to illustrations to aid understanding of the present invention, and the present invention is not limited to these illustrations, but includes the claims. It is limited only by the range, and other changes and modifications can be made within that range.

[Brief explanation of the drawing]

Figure 1 shows the XR spectrum of an example of a polydimethylsiloxane obtained by the method of the present invention and having a radical at both ends.
Figure 2 is a block copolymer obtained by the method of the present invention using amino-terminated FDMS (according to Production Example I in the text). Figure J is an XR spectrum diagram of the block copolymer obtained in Production Example J [also shown in the text, Figure 9 is an XK spectrum diagram of the block copolymer obtained in Production Example J, and Figure S is a block JR spectrum diagram of nine products obtained by modifying the amino acid block of the copolymer (product of reaction example 1 in the text), and Figure 6 is an XR spectrum diagram of the product of reaction example 1, also in the text. , #g7 figure shows Pretsuta copolymer ηλ
In the chart for Om1 to 7 times, which is a mu TR-IR spectrum diagram of a film obtained by modifying a film formed from ) The vertical axis shows the transparency 0 8:4! . Shoulder Figure 3, Figure 5, Figure 7 Amendment to figure procedure (voluntary) February 12, 1978 / Indication of the case Patent application No. Shoj 6-λ036￥0 λ Name of the invention Polydimethylsiloxane having amine groups at both ends Manufacturing method 3 Relationship with the case of the person making the amendment Patent applicant name Yuki Konishi Agent J Target of amendment 1 Change column H of “Detailed description of the invention” in the specification to “0.7 to 0 .Correct to 2% KOHJ〇(2
) Same No. 1/page? Row [(za00 cm -') J
is corrected as "(?θocm-ri"). (Correct the bottom end of the structural formula on page 12 of the same, page 31. (41, page 16 of the same, lines 2-3) (5) Change "100" from the first line from the bottom of page 72 to "several tens".
I am corrected. (6) Correct "ATB-EngR" in lines B to j from the bottom of page 23 to read "ATR-EngR". (7) "Antithrombotic" in the seventh line from the bottom of page 25 is corrected to "antithrombotic."that's all

Claims (1)

[Claims] A method for producing polydimethylsiloxane having amino groups at both ends, which comprises polymerizing octamethylshifftetracytetraquinane in the presence of bis(J-amineprobyl)tetramethane having amino groups at both ends.