AU681515B2 - Degradation resistant poly(ether esters) and processes for producing the same - Google Patents

Description

WO 95/29201 PCT/AU95/00230 I

-I-

DEGRADATION RESISTANT POLY(ETHER ESTERS) AND PROCESSES FOR PRODUCING THE SAME The present invention relates to poly(ether esters) which are degradation resistant, and processes for manufacturing the same, and articles produced therefrom.

Thermoplastic polyether based polyesters are generally susceptible to oxidative and hydrolytic degradation. In addition, in the absence of antioxidants, copolyester elastomers are rapidly degraded in air at elevated temperatures.

Conventional polyester elastomers are subject to oxidative degradation when exposed to ultra violet light, and as a result of their polar nature, they are also subject to degradation by hydrolysis at elevated temperatures.

US patent 3,023,192 discloses fibers that are formed from copolyether ester units prepared by the reaction between one or more dicarboxylic acids or their ester forming derivatives, one or more difunctional polyethers and one or more dihydroxy compounds which include lower aliphatic glycols having the general formula:

HO(CH

2 )aOH where a is from 2 to Representative of the difunctional polyethers which may be used include poly(alkylene oxide) glycols such as: poly(heptamethylene oxide)glycol, poly(hexamethylene oxide) glycol, poly(octamethylene oxide)glycol, poly(nonamethylene oxide)glycol and poly(decamethylene oxide)glycol.

The synthetic fibers formed by the method of US 3,023,192 have an ability for a high degree of elastic recovery and are particularly suitable in the textile WO 95/29201 PCT/AU95/00230 -2industry. There is no indication however that the copolyether ester elastomers are especially degradation resistant. In fact the polyesters usually incorporate stabilisers in order to stabilise the composition to heat and ultra violet radiation.

A copolyether ester with increased resistance to oxidative degradation is disclosed in US patent 3,856,749. Such copolyether ester compositions are prepared with the use of poly(alkylene oxide) glycols having a carbon to oxygen ratio of about 2.0-4.3. The stability of the composition is achieved by incorporating from 0.01 to 7.0 wt% of a urea linkage between long chain and short chain ester units. Examples of the long chain glycols that are utilized include poly(ethylene oxide) glycol, poly(1,2- and 1,3-propylene oxide) glycol, poly(tetramethylene oxide) glycol, random or block copolymers of ethylene oxide and 1,2-propylene oxide, and random or block copolymers of tetrahydrofuran with minor amounts of a second monomer such as 3-methyltetrahydrofuran. Such polymeric glycols have a molecular weight of from about 400 to 6000. Particularly preferred is poly(tetramethylene oxide)glycol.

Such materials require stabilisers toward hydrolysis and oxidation even for use in relatively mild environments. The limited hydrolytic and oxidative stability, for example prevented the materials for being used for chronic medical implants, and other areas where a hostile environment may exist.

European patent 210281 discloses non-adsorbable high strength sutures or ligatures comprising a poly(ether ester), in which the ester has alkylene oxide groups containing from 1-10 carbon atoms.

It has been found however, that articles with improved degradation resistance can be produced by correct selection of the poly(alkylene oxide) during the process of manufacture. The present invention aims to overcome or at least alleviate one or more of the difficulties associated with the prior art.

According to a first aspect of the present invention, there is provided a degradation resistant poly(ether ester) derived from: PCT/AU 95 002 3 0 RECEIVEU 1 9 OCT 1995 -3a polyether macroglycol; and a low molecular weight dicarboxylic acid or ester forming species derived therefrom; wherein the poly(ether ester) is prepared from a polyether macroglycol having alkylene ether repeating units containing 6 to 10 carbon atoms.

In a preferred embodiment of the invention, the polyether macroglycol is poly(hexamethylene oxide) glycol, poly(octamethylene oxide) glycol or poly(decamethylene oxide) glycol. Most preferred is poly(hexamethylene oxide) glycol. It has been found that by utilizing these particular polyether macroglycols in accordance with the invention, that the polymers so produced exhibit particular degradation resistance in hostile environments.

The poly(hexamethylene oxide) glycol, or indeed any other required macroglycol, may be prepared in a manner as disclosed in Australian patent 642799. This process involves providing a suitable polyhydroxy compound and reacting the compound in the presence of an acid resin catalyst, such as Nafion- HTM. The polyhydroxy compound is not critical and may be for example branched or unbranched, cyclic or linear, substituted or unsubstituted or contain one or more hetero atoms in the main chain. Suitable polyhydroxy compounds may include 1,6 hexanediol, 1,4-cyclohexanediol, 1,8 octanediol, octafluoro-1,6-hexane diol, or 1,10-decanediol.

This process is usually carried out at a temperature in the range of from 130 0 C to 220 0 C, and the degree of polymerisation is controlled by the presence of the catalyst. For the purpose of the present invention, poly(alkylene oxides) having molecular weights of from 400 to 10,000 may be produced. Particularly preferred are poly(hexamethylene oxide) having a molecular weight of from 800 to 1200.

The low molecular weight dicarboxylic acid or ester forming species Sderived therefrom, may be the product of the reaction of a low molecular weight AMENDED SHEET

IPEA/AU

PCT/AU 95 00 2 3 0 RECliV U 9 OCT 195 -4diol and a dicarboxylic acid, acid halide or anhydride. The diol will usually have a molecular weight of below about 250.

The ester forming dicarboxylic acid derivative itself may be an ester or a half ester of a low molecular weight alcohol.

The poly(ether ester) may be derived from a composition including a low molecular weight diol. Included among the low molecular weight diols suitable for the preparation of the poly(ether ester) of the invention, are aliphatic, cycloaliphatic, and aromatic dihydroxy compounds. Preferred are diois with 2 to carbon atoms such as butanediol, ethylene, propylene, butylene and tetramethylene glycols. In particular aliphatic diols containing 2 to 8 carbon atorms are preferred.

The poly(ether esters) of the invention are formed by the polymerisation reaction between the poly(alkylene oxide) glycol and the low molecular weight dicarboxylic acid or ester forming species derived therefrom. A low molecular weight diol may be present to provide elastomeric properties for the polymer.

The ester forming dicarboxylic acid derivative may be aliphatic, cycloaliphatic or aromatic with preferably a molecular weight of less than 550, most preferably less than 300. Most preferably, aromatic dicarboxylic acids are used, having from 8 to 16 carbon atoms particularly phenylene dicarboxylic acids, for example phthalic, terephthalic and isophthalic acids or derivatives thereof.

Representative of the aliphatic or cycloaliphatic dicarboxylic acids that may be used include sebacic acid, cyclohexane carboxylic acids, adipic acid, glutaric acid, and succinic acid and or derivatives thereof.

The reaction and the reaction product may also include an antioxidant.

Suitable antioxidants that may be used include aryl and diaryl amines, ketone aldehyde amine condensates, and hindered phenol antioxidants.

AMENDED SHEET IPFAWI.1 P'/AU 9 5 i /002 3 0 RECEIVEIE I OCT Y Suitable diaryl amines include phenyl naphthylamines and octylated diphenylamine and 4-iso-propoxydiphenylamines. P-pheny!enediamine derivatives such as N,N'-bis-1-methyl-heptyl-p-phenylenediamine and N,N'-dibeta-naphtyl-p-phenylenediamine are also preferred.

Generally, the macroglycol will constitute from 5 to 85% by weight, preferably 10 to 75% by weight of the poly(ether ester); the low molecular weight dicarboxylic acid or ester forming species may constitute from 15 to 95% by o0 weight, preferably 25-90% by weight of the poly(ether ester). The low molecular weight diol may be added in a molar ratio of from 0.1:1 to 10:1 of the dicarboxylic acid or its derivative, the excess (if any) being distilled off during polymerisation such that the final polymer may include from 0 to 20% by weight of the low molecular weight diol residue. The antioxidant is generally present in an amount 1i of from 0 to 5 by weight.

Accc.ding to a further aspect of the present invention, there is provided a process for the production of degradation resistant poly(ether ester) which includes reacting: a polyether macroglycol; and a low molecular weight dicarboxylic acid or ester forming species derived therefrom; to form a poly(ether ester), wherein the polyether macroglycol has alkylene ether chain units containing 6 to 10 carbon atoms.

It is most preferred in the processes, to select the polyether macroglycol from poly(hexamethylene oxide) glycol, poly(octamethylene oxide) glycol or poly(decamethylene oxide) glycol. Most preferred is poly(hexamethylene oxide) glycol.

The poly(ether ester) may be manufactured according to known ester interchange reaction processes, for example those described in United States Patent 3,856,749. A preferred procedure may include heating the dicarboxylic AMENDED SHEET

IPEA/AU

PCT/AU 9 5 0 0 2 3 0 RECEIVLU I J OCT 19 -6ester with a poly(hexamethylene oxide) of molecular weight of from 800 to 1200, and a molar excess of a diol in the presence of a catalyst, at a temperature of from 1300 to 2900 and a pressure of from 0.5 to 5 atmospheres, preferably ambient pressures until the alcohol from the ester exchange is distilled. This reaction will generally take from 2 minutes to 2 hours depending upon conditions.

Generally the molar ratio of the components may be from 1 mol of acid:0.25 to 0.85 mol of poly(hexamethylene oxide): greater than 1 mol of diol. The optional antioxidant may be included at any time during the reaction.

Distillation of the excess diol will result in 'polycondensation' to the poly(ether ester). This step is usually conducted at a temperature of from 180 0

C-

270 0 C for 1/2 to 2 hours at less than 5mm pressure.

The process is able to produce polymers which may be shaped or formed by conventional methods to make degradation resistant articles of poly(ether ester) based polyesters. Such polyesters are particularly useful for use in harsh degradation producing environments. For example, they have particular application in medical devices, including insulation for medical electrical leads and long term indwelling catheters and vascular prosthesis. Other non-medical applications include long term or severe exposure to degradative environments, such as oil rig or chemical plant hosing. The polyesters also show improved thermal processing through their greater oxidation resistance.

The polymers of the present invention are suitable for harsh environments with a potential use in the broad number of applications, including monofilaments and fibers including optical fibers, vascular grafts, medical implants, surgical prosthesis, sutures, catheters, artificial leather, flexible boots, shoe soles, sporting equipment, cable sheathing and hosing.

The following examples'are illustrative of the present invention, and the scope should not be considered to be limited thereto.

SAMENDED SHEET

IPEA/AU

PCT/AU 9 5 0 0 2T REUIfVLU I J OC 13 -7- EXAMPLE 1 Poly(hexamethylene oxide) of number average molecular weight 950 is dried by heating at 105 °C for 15 hours at 0.1 Torr. Anhydrous butanediol (19.6 dimethylterephthalate (30.5 the pre-dried polyhexamethylene glycol (51.3 g) and sym-di-p-naphthyl-p-phenylenediamine (0.15 g) are added to a nitrogen blanketed reaction flask at 2000C equipped for efficient mechanical stirring and set up for distillation. After five minutes of stirring, at which time the mixture becomes molten, n-tetrabutyl titanate (0.3ml) is added. Methanol distillation starts iu almost immediately and is complete within 20 minutes. The temperature is maintained for a further one hour and then is increased over 30 minutes to 250 0

C.

The pressure is then reduced to 0.1 Torr and distillation at reduced pressure is continued for a further 90-120 minutes. The resulting viscous slurry is scraped from the flask under an atmosphere of nitrogen or argon and allowed to cool.

This procedure yields 80.6 g of a polymer, designated as Material A, of inherent viscosity 0.81 dl/g, which is suitable for thermoforming into a degradation resistant article. Material A was compression moulded on a Wabash Press at 180 OC (and a nominal load of 8 Tons) into sheets, from which dumbbell-shaped.test pieces were cut using a specially manufactured punch.

COMPARATIVE EXAMPLE 1 A method identical with that described in Example 1, except that pre-dried poly(tetramethylene oxide) (54 g) of number average molecular weight 1000 replaced the poly(hexamethylene oxide), to prepare the poly(ether ester. This poly(ether ester) is of the type typically used for preparing articles according: to the prior art. This polymer, designated as Material B, had an inherent viscosity of 1.04 di/g and could be compression moulded at 180 °C into sheets, from which dumbbells could be cut.

The comparative mechanical properties are shown below: 34 AMENDED SHEET

SIP.NAU

PC/AU 95 00230 RECEIVED 19 OCT 1995 Ultimate Tensile Stress 8.1 MPa 10.4MPa Ultimate Strain 143% 3 3 00/q Stress at 100% Strain 7.8 MPa 8.7 MPa Material A Material B Material A exhibited characteristics expected of a degradation resistant material, whilst Material B, which is representative of the prior art, did not. For example, Material A exhibited good hydrolytic stability when tested by boiling 0io weighted dumbbells for 6 days in pH1 7, pH I and pH 13 buffer solutions. After washing with water and drying, the dumbbells showed an average 10%, 87% and 40% decrease in ultimate tensile stress for the three treatments, respectively, whereas the corresponding decreases for Material B were 26%, 100% and respectively.

The decreases in ultimate tensile stress for dumbbells prepared from a commercial sample of Hytrel (registered trademark) subjected to these conditions were 59%, 96% and 95%, respectively. Dumbbells of Material A also showed good oxidative stability when tested in 50% hydrogen peroxide solution at 37 0

C

for 24 hours. After washing with water and drying, the dumbbells showed an average 19% decrease in ultimate tensile stress, whereas the corresponding decreases for the dumbbells of Material B and of commercial Hytrel were both 94%.

The relative stabilities are shown in Charts 1 and 2.

AMENDED SHEET

IPENAU

wo 95/29201 WO 9529201PCT/AU95OO230 9- Chart 11. Polyester Hydrolytic Stability at 100 0 C (6 days) 1- 0.8- 0.6- 4 *1- H ytre I Material B (PTMO-based) Material A (PHMO-based)

IV

p H7(r) pHI 3 pHi Chart 2. Poly(ether ester) Stability to Hydrogen Peroxlde at 37 OC (24 h) 76

I(

0,j SUBST1UM SHEE (Mie 26) WO 95/29201 PCT/AU95/00230 EXAMPLE 2 A poly(decamethylene oxide) polyester incorporating 52% of the polyol was made using the procedure described in Example 1 (64% polyol) except with the following levels of starting reagent-..poly(decamethylene oxide) (MW is 960) 39.2g dimethylterephthalate 37.6g butanediol 19.63g sym-di-p-naphthyl-p-phenylenediamine 0.1 Og n-tetrabutyl titanate 0.22ml This procedure yields 72g of a polymer, designated as material C, which could be compression moulded at 1950C into sheets from which dumbbells were cut.

COMPARATIVE EXAMPLE 2 A poly(tetramethylene oxide) polyester incorporating 52% of the polyol was also made using the procedure of Example 1. The following levels of starting reagents were used:poly(tetramethylene oxide) (MW is 980) 107.7g dimethylterephthalate 103.1g butanediol 55.0g sym-di-p-naphthyl-p-phenylenediamine 0.3g n-tetrabutyl titanate 0.6ml This procedure yielded 200g of a polymer designated below as Material D.

The comparative mechanical properties were: WO 95/192,31 PCT/AU95/00230 I I Ultimate Tensile Ultimate Strain Stress at 100% Toughness Strength Strain Material C 11.4 MPa 143% 12.0 MPa 16.5 MPa Material D 12.4 MPa 165% 12.8 MPa 19.0 MPa As demonstrated below Material C exhibited characteristics expected of a degradation resistant material, whilst Material D, which is representative of the prior art, did not.

Hydrogen Peroxide Resistance Material C exhibited good oxidative resistance when heated at 80 0 C in hydrogen peroxide solution at pH 1.6 for 7 hours. After washing with water and wiping dry, the dumbbells (x5) showed only an average 16% decrease in ultimate tensile stress. Material D and a commercial poly(ester ether) Hytrel (registered trade mark) when subjected to these same conditions were partially digested by the hydrogen peroxide and lost all cohesive strength.

Resistance to Oxygen at Elevated Temperature The materials were dried to constant weight at 60°C at 0.1 Torr for 12 hours and then heated at 200°C in an atmos'here of pure oxygen using a Mettler thermogravimetric analysis apparatus which enabled continuous monitoring of weight loss. The results in the table below demonstrate that the polyether ester polymers of the invention are significantly more resistant to high temperature oxidation that the prior art materials.

Material Weight Loss in Oxygen at 200 C 1 hour 2 hour 3 hour C 0.6% 1.2% 1.8% D (prior art) 1.5% 2.9% 3.9% WO 95/29201 PCT/AU95/00230 -12- Hydrolytic Stability in Strong Acid Material C exhibited good hydrolytic stability when tested by boiling weighted dumbbells for six days in pH 1 buffer solution. After washing with water, wiping dry and testing for tensile properties, the dumbbells showed an average of 7% decrease in ultimate tensile stress and an average 51% decrease in ultimate strain. The corresponding decreases for Material D, typical of a prior art material, were 18% in ultimate tensile stress and 80% in ultimate strain.

ic Resistance to alkali Material C exhibited good hydrolytic stability when tested by boiling weighted dumbbells for six days in pH 13 buffer solution. After washing with water, wiping dry and testing for tensile properties, the dumbbells showed an average 2% decrease in ultimate tensile stress and an average 56% decrease in ultimate strain for the two treatments respectively. The corresponding decreases for Material D, typical of a prior art material, were 28% in uIm ate tensile stress and 60% in ultimate strain.

EXAMPLE 3 A poly(hexamethylene oxide) polyester incorporating 52% of the polyol was made using the procedure described in Example 1 except with the following levels of starting reagents:poly(hexamethylene oxide) (MW is 960) 107.9g dimethylterephthalate 103.4g butanediol 54.4g sym-di-p-naphthyl-p-phenylenediamine 0.30g n-tetrabutyl titanate 0.6ml WO 95/29201 PCTIAU95/00230 13 This procedure yielded 200g of a polymer which was compression moulded at 195 0 C into sheets from which dumbbells were cut. The polymer had the following mechanical properties: Ultimate tensile strength 12.0 MPa Stress at 100% strain 11.7 MPa Ultimate strain 225% Toughness 24.5 MPa

Claims (29)

1. A degradation resistant poly(ether ester) derived from: a polyether macroglycol, and a low molecular weight dicarboxylic acid or ester forming species derived therefrom; wherein the poly(ether ester) is prepared from a polyether macroglycol having alkylene ether repeating units containing 6 to 10 carbon atoms.

2. A degradation resistant poly(ether ester) according to claim 1 wherein the polyether macroglycol is poly(hexamethylene oxide) glycol, poly(octamethylene oxide) glycol or poly(decamethylene oxide) glycol.

3. A degradation resistant poly(ether ester) according to claim 2 wherein the polyether macroglycol is poly(hexamethylene oxide) glycol.

4. A degradation resistant poly(ether ester) according to claim 1 wherein the polyether macroglycol derived portion of the poly,ether ester) constitutes 5 to of the polym3r by weight and the portion derived from the dicarboxylic acid or ester forming species derived therefrom constitutes 15 to 95% by weight.

A degradation resistant poly(ether ester) according to claim 4 wherein the polyether macroglycol derived portion of the poly(ether ester) constitutes 10 to of the polymer by weight and the portion derived from the dicarboxylic acid or ester forming species derived therefrom constitutes 25 to 90% by weight.

6. A degradation resistant poly(ether ester) according to claim 1, wherein the ester forming dicarboxylic acid derivative is itself an ester or half ester of a low molecular weight alcohol.

7. A degradation resistant poly(ether ester) according to claim 1, wherein the ester forming dicarboxylic acid derivative is aliphatic, cycloaliphatic or aromatic and is a diacid halide, or anhydride. PCr/AU 9 5 02 3 0 E JVyEO 19 OCT 1995

8. A degradation resistant poly(ether ester) according to claim 1, wherein the ester forming dicarboxylic acid derivative is an aromatic compound having from 8 to 16 carbon atoms.

9. A degradation resistant poly(ether ester) according to claim 8, wherein the ester forming dicarboxylic acid derivative is a phthalic, isophthalic or terephthalic acid derivative.

10. A degradation resistant poly(ether ester) according to claim 1, wherein the ester forming dicarboxylic acid derivative is an aliphatic, or cycloaliphatic compound which is a sebacic acid, cyclohexane carboxylic acid, adipic acid, glutaric acid, or succinic acid derivative.

11. A degradation resistant poly(ether ester) according to any one of claims 1 to 10, further including up to 5% by weight of an antioxidant.

12. A degradation resistant poly(ether ester) according to any one of claims 1 to 11 also derived from a low molecular weight diol.

13. A process for the production of degradation resistant poly(ether ester) which includes reacting: a polyether macroglycol; and a low molecular weight dicarboxylic acid or ester forming species derived therefrom; to form a poly(ether ester), wherein the polyether macroglycol has alkylene ether chain units containing 6 to 10 carbon atoms.

14. A process according to claim 13 wherein the polyether macroglycol is poly(hexamethylene oxide) glycol, poly(octamethylene oxide) glycol or poly(decamethylene oxide) glycol.

IP r d 0 I( AMENDED SHEET IPEA/AU WO 95/29201 PCT/AU95/00230 -16- A process according to claim 14 wherein the polyether macroglycol is poly(hexamethylene oxide) glycol.

16. A process according to claim 13 wherein the polyether macroglycol constitutes 5 to 85% of the reaction mixture by weight and the dicarboxylic acid or ester forming species derived therefrom constitutes 15 to 95% by weight:

17. A process according to claim 16 wherein the polyether macroglycol constitutes 10 to 75% by weight and the dicarboxylic acid or ester forming species o1 derived therefrom constitutes 25 to 90% by weight.

18. A process according to claim 13 wherein the ester forming dicarboxylic acid derivative is itself an ester or half ester of a low molecular weight alcohol.

19. A process according to claim 13 wherein the ester forming dicarboxylic acid derivative is aliphatic, cycloaliphatic or aromatic and is a diacid halide, or anhydride.

A process according to claim 13 wherein the ester-forming dicarboxylic acid derivative is an aromatic compound having from 8 to 16 carbon atoms.

21. A process according to claim 20 wherein the ester-forming dicarboxylic acid derivative is a phthalic, isophthalic or terephthalic acid derivative.

22. A process according to claim 13 whereii. the ester-forming dicarboxylic acid derivative is an aliphatic, or cycloaliphatic compound which is a sebacic acid, cyclohexane carboxylic acid, adipic acid, glutaric acid, or succinic acid derivative.

23. A process according to any one of claims 13 to 22 wherein up to 5% by weight of an antioxidant is added to the reaction mixture of the resulting polymer.

24. A process according to any one of claims 13 to 23 further including a diol in the reaction mixture.

PCT/AU 95 0 RECEirij'iiQ -W -17- A device or article having improved durability in hostile environments which includes the degradation resistant poly(ether ester) according to any one of claims 1 to 12.

26. A medical device article or implant which includes the degradation resistant poly(ether ester) according to claim 1.

27. A medical device article or implant according to claim 26 which is an o0 insulated electrical lead, a coated optical fibre, a suture, a long term in-dwelling catheter, or a vascular prosthesis.

28. An artificial leather, sporting equipment, shoe sole, monofilament, hose or cable sheathing which includes the degradation resistant poly(ether ester) according to claim 1.

29. A degradation resistant poly(ether ester) according to claim 1, substantially as hereinbefore described with reference to any one of the non- comparative examples. A process, according to ciaim 13 substantially as hereinbefore described with reference to any one of the non-comparative examples. AMENDED SHEET IPEANAU INTERNATIONAL SEARCH REPORT International application No. PCT/AU 95/00230 A. CLASSIFICATION OF SUBJECT MATTER Int. Cl. 6 C08G 63/668 63/672 According -a International Patent Classification (IPC) or to both national classification and IPC B. FIELDS SEARCHED Minimum documentation searched (classification system followed by classification symbols) IPC C08G 63/66, 63/668, 63/672 Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched AU IPC as above Electronic data base consulted during the international search (name of data base, and where practicable, search terms used) C. DOCUMENTS CONSIDERED TO BE RELEVANT Category* Citation of document, with indication, where appropriate, of the relevant passages Relevant to Claim No. Patent Abstracts of Japan, C-1266, page 100, JP,A, 6-206991 (TEUIN LTD) 26 July 1994 P,A abstract 1-12 Derwent Abstract Accession No. 94-106992/13, Class X12, JP,A, 08-057153 (DAICEL CHEM IND LTD) 1 March 1994 A abstract 1-12 AU 90391/91 (642799) (COMMONWEALTH SCIENTIFIC AND INDUSTRIAL RESEARCH ORGANISATION) 25 June 1992 A pages 1 and 2 1-12 S Further documents are listed IX See patent family annex. in the continuation of Box C. Special categories of cited documents later document published after the international filing date or priority date and not in conflict document definin the general state of the art which is with the application but cited to understand the not considered tobe ofparticular relevance principle or theory underlying the invention earlier document but published on or after the document of particular relevance; the claimed international filing date invention cannot be considered novel or cannot be document which may throw doubts on priority claim(s) considered to involve an inventive step when the or which is cited to establish the publication date of document is taken alone another citation or other special reason (as specified) document of particular relevance: the claimed document referring to an oral disclosure, use, invention cannot be considered to involve an exhibition or other means inventive step when the document is combined document published prior to the international filing date with one or more other such documents, such but later than the priority date claimed combination being obvious to a person skilled in the art document member of the same patent family Date of the actual completion of the international search Date of mailing of the international search report 3 August 1995 s AuGus 1qq (oo08.08. 9 Name and mailing address of the ISA/AU Authorized officer AUSTRALIAN INDUSTRIAL PROPERTY ORGANISATION PO BOX 200 WODEN ACT 2606 AUSTRALIA L. MENZ Facsimile No. 06 2853929 Telephone No. (06) 2832431 Form PCT/ISA/210 (continuation of first sheet (July 1992) cophin I INTERNATIONAL SEARCH REPORT Information on patent ft1nily membei International application No. PCT/AU 95/00230 This Annex lists the known publication level patent family members relating to the patent documents cited in the above-mentioned international search report. The Australian Patent Office is in no way liable for these particulars which are merely given for the purpose of information. Patent Document Cited in Search Patent Family Member Report AU 90391/91 EP 559739 JP 6503113 NZ 240740 us 5403912 WO 9209647 END OF ANNEX Form PCT/ISA210(patent family annex)XJuly 1992) cophin