The invention relates to a set for inserting a shunt valve into a surgically produced connecting channel between the trachea and the oesophagus of a laryngectomee. The shunt valve has at least two flexible, rolled up fixing strips at the oesophagus end. The fixing straps can be unrolled after introduction into the connecting channel and then rest against the oesophagus wall. The set has a support with a proximal, essentially cylindrical coupling piece on which the shunt valve is placed, and a holding and releasing element, which releasably holds the at least two fixing straps in their rolled-up position and releases them when activated.

The invention concerns a set for the insertion of a shunt valve in a surgically created connecting channel (shunt) between trachea and oesophagus of a laryngectomized patient.
The insertion of shunt valves has been known for a long time. A shunt valve of this kind is known, for example, from the applicant""s recent German patent application 196 51 951. Usually the shunt valves have two circular flanges, of which one flange comes to lie on the oesophagus wall and the other flange comes to lie on the trachea wall after the insertion into the connecting channel.
Instead of the circular flange on the side of the esophagus, more recent developments have larger, more flexible holding straps, which quasi unfold in the radial direction after the insertion of the valve, and lie flush against the esophagus wall, in order thus to provide for a more sure hold of the valve in the connecting channel.
In this case the way in which a shunt valve with enlarged holding straps can be used at all in the connecting channel without being very unpleasant or even painful for the patient is a problem. Basically the main difficulty with the insertion of the valve into the connecting channel consists in rolling the flexible great holding straps which are separated from the main axis of the valve in a suitable way and letting them unfold only after the use of the valve.
Since this is not possible manually, an instrument or holder must be used for the shunt valve. A proposal to hold the above-mentioned holding straps in the rolled together condition during the insertion envisions holding the holding straps in the corresponding condition by means of a digestible adhesive. In the course of time after the insertion of the shunt valve the adhesive dissolves and the holding straps unfold in the envisioned way. However, the moment of the unfolding cannot be determined exactly, from which problems can develop.
Against this background, the object of the invention is to create a complete set for the insertion of a shunt valve, with which trouble-free insertion into the operatively created shunt is possible and which facilitates the process of insertion for the treating person.
The object is solved by the set according to claim 1. Advantageous further developments are cited in the subclaims.
In general a set for the insertion of a shunt valve in a surgically created connecting channel between the trachea and oesophagus of a laryngectomized patient is proposed, on the oesophagus side the shunt valve having at lest two flexible holding straps rolled together, which can be straightened out after the insertion in the connecting channel and lie against the oesophagus wall, having a holder with a proximal, essentially cylindrical coupling piece, on which the shunt valve is set, as well as a holding and releasing element, which holds the at least two holding straps capable of being related in the rolled together position and releases the holding straps for operation.
Accordingly, the essential feature of the invention is that the holding and releasing element is both the element which holds the at least two holding straps rolled together, as well as the element with which the unfolding of the holding straps is released in situ.
The concrete configuration of the invention is reflected in two embodiments described below.
According to a first preferred embodiment it is provided that the holding and releasing element is a guide rod with a spherical proximal end which can be moved, penetrating the essentially cylindrical coupling piece, which is capable of being set into the holding straps rolled together through openings and prevents the holding straps from unfolding without pulling, respectively pulling back, the guide rod.
This second embodiment is suited particularly for reusing, respectively for resupplying a patient, for example with a cleaned shunt valve in a medical practice. For this the physician can equip the instrument with a shunt valve in a simple way, roll up the indicated holding straps, and hold or stop the latter in their position by guiding the guide rod with its spherical end through the openings into the holding straps. The flexible material of the holding straps is stretched when the spherical end of the guide rod is guided through, so that the openings with small diameter in the holding straps are widened at the time of xe2x80x9cloadingxe2x80x9d the instrument, and pulled back again, so that the rolled together holding straps are held in their position.
The release is achieved in the case of this second embodiment in a simple way by pulling on the back end of the guide rod, whereupon the spherical end of the guide rod passes through the openings in the holding straps with elastic widening of the material of the holding straps, and so the stopping action of the spherical end of the guide rod is ended. The elastic material of the shunt valve makes sure that at this moment the holding straps are unfolded in the way provided and described.
The use of the set according to this embodiment by the treating person corresponds to the use of the first embodiment of the set up to the release process.
According to a second preferred embodiment it is provided that the holding and release element is a pull thread with a first free end, which is guided along the holder to the coupling piece, emerges from the latter and which holds at least two holding straps releasably in the rolled together position, enters the coupling piece again, and is guided back along the holder, where it forms an operating end with its second free end.
In the case of this embodiment the release takes place in the simplest way by pulling on the operating end of the pull thread, whereupon the first free end of the thread is pulled in the direction to the coupling piece and the rolled together holding straps and from there back again in the direction of the coupling piece. If the pull thread was pulled so far on the operating end that the first free end of the pull thread has passed both holding straps, the flexible material of the holding straps is relaxed and the latter on the oesophagus side line against the oesophagus wall. The pull thread holds the holding straps in the rolled together condition essentially by the simple effect of friction. For this, the holding straps in each case can have a hole, through which the pull thread passes in each case.
The use of the set by the treating person takes place in the following way:
The treating person takes the sterile-packed set out of the packaging, and holds in one hand the ready-to-use set, which has the shunt valve with rolled-together holding straps ready to be inserted. The set is guided proximally through the tracheostoma on the connecting channel, the shunt valve is set with the rolled together holding straps through the channel until the valve has assumed the correct position. Then the person pulls on the operating end of the pull thread until the thread has been completely pulled out of the holder, so that in each case the holding straps can lie flush against the oesophagus wall and thus provide for a more secure hold.
According to an advantageous embodiment it is provided that the pull thread is guided along the back of the holder in a groove and by a guide hole at the height of the coupling piece in the latter, emerges at the end thereof, forms a loop passing through the holding straps, enters the hole again, and is guided down in the groove along the holder. By guiding the pull thread in the groove in the back, the pull thread is subject to a certain guiding. In addition the set can be made as a compact unit as a disposable article, without the pull thread being capable of being knotted or tangled detrimentally in use.
The last effect is supported advantageously by the fact that in the set according to a further development the pull thread is held in the groove holders surrounding the holder.
Advantageously the operating end of the pull thread is provided with a pull ring. This facilitates the operation of the set considerably, since the treating person only has to reach for the pull ring and does not have a difficult time finding the end of the pull thread.
Both embodiments described can be made advantageously so that the holder passes longitudinally stretched from the distal handle end and is bent into a bow to the proximal parts, then in order to pass out in the coupling piece or to end, the main axis of the coupling piece being at an angle between 70 to 90xc2x0 to the longitudinal axis of the grip end. The shape of the holder facilitates the handling of the set, namely the proximal end on which the prepared shunt valve rests can be guided through the tracheostoma to the connecting channel between the trachea and esophagus. The bent shape also facilitates the visual monitoring by the treating person with respect to the correct guiding and position of the valve.
The embodiment with the holding and releasing element made as a guide rod according to the above-mentioned further development can be particularly preferably improved by means of the fact that the guide rod emerges on the back side from the above-mentioned bow and is hinged to an operating strap, which for its part is held capable of swiveling on the holder.
This simple mechanism permits easy handling of the set by the treating physician. In the loaded condition of the set, with shunt valve placed with the holding straps rolled together, the guide rod is pushed into its maximum displacement position. The swivel holding of the operating strap now is made so that, for example, the treating physician pushes on the end thereof, whereupon the operating strap is swiveled in such a way that the guide rod is pulled back out of this maximum position, the proximal spherical endxe2x80x94as describedxe2x80x94with expansion of the material penetrates the openings in the holding straps, whereupon the holding straps unfold.

Set for inserting a shunt valve into a shunt between the oesophagus and the trachea

Adeva Medical Gesellschaft fur Entwicklung und Vertrieb Von Medizinischen Implantat-Artikeln mbH


A thermal insulation system for insulating a pipe is disclosed having an upper insulation member engageable with a lower insulation member to collectively surround the pipe. Each of the upper and lower insulation members preferably have a plurality of constant radius relief cuts at each end thereof, wherein the constant radius relief cuts extend from the end of each of the insulation members toward the center of the insulation member. In a preferred embodiment, each insulation member further includes a plurality of radial relief cuts extending radially from the inner surface of each of the insulation members toward the outer surface of the insulation member. The radii of curvature of the insulation members is preferably variable such that, for a portion of the insulation member, a gap exists between the inner surface of the insulation member and the pipe, allowing room for fluctuation in the size and shape of the insulation members.

The present invention relates generally to thermal insulation systems for piping, and more particularly to a factory jacketed thermal pipe insulation having relief cuts therein to compensate for fluctuations in form resulting from varying environmental factors.
Pipes that convey liquid or gaseous materials from one point to another often require insulation and protection from environmental elements such as heat and cold. Insulation is especially important in industrial and critical process applications. To protect against the elements, one option has been to provide piping with the insulation already installed thereon. Thus, piping and insulation are made available as a combined unit. The purchase of the pipe and insulation as a combined unit ensures that the insulation will fit the pipe perfectly. However, when the pipe needs repair or maintenance, the process of removing and replacing the insulation is difficult and time consuming.
To simplify the insulation process, a factory jacketed insulation system is available, separately from the pipes. The factory jacketed insulation system allows the user the option of the installation of a wider variety of piping of various construction and materials without the necessity of purchasing the piping and insulation as a combined unit. The factory jacketed insulation system includes a first semi-circular section that is dimensioned to mate with a second semi-circular section. The two semi-circular sections are permanently bonded to a single exterior jacket to complete the insulation system. The first and second sections have corresponding notches at the ends for easy fit and mating. The factory jacketed insulation system can be installed by simply pressing the first semi-circular section around half of the pipe and wrapping the second section over the remaining pipe thereby joining the first and second sections together. The factory-applied jacket allows for precision mating of the two insulation sections. There is no need to remove the pipe when installing the insulation. Furthermore, the pipe and the insulation need not be purchased together as a combined unit. The slide-over arrangement also allows for simplified testing of the installation for leakage and repair of the pipes.
The disadvantage of the factory jacketed insulation system is that the insulation material is sensitive to the moisture content in the ambient air. In a dry environment, the insulation material is at its smallest condition. When the humidity rises, the insulation material expands. A 30% rise in humidity could result in a 3% increase in the size of the material. The fluctuation in the size of the insulation material interferes with the fit around the pipe. The problem is magnified for larger pipes since there is an increase in the surface area.
This problem is illustrated in the manufacturing/sale scenario. The manufacturer, located in a first city, cuts the insulation to the customer""s specifications. The insulation is then shipped to a second city having a different ambient air moisture level than the first city. When the insulation arrives at the second city, it will have fluctuated in size and will no longer fit around the pipe. The unsatisfied customer will undoubtedly complain to the manufacturer and return the insulation for evaluation. Upon arrival in the first city, the insulation will return to its original size, evading a negative analysis. The manufacturer is not able to respond to the customer""s complaint.
The problem can arise even if the insulation is not shipped to another city. For instance, insulation that is cut in humid temperatures is swollen and contains water. Once the insulation is placed on a hot pipe, the water evaporates causing the insulation to shrink. If a jacket is placed around the insulation, the contraction of the insulation will cause the jacket to wrinkle.
Accordingly, there is a need for a thermal insulation system that is easy to install and accommodates fluctuation in size of the insulation resulting from changes in temperature and humidity.
The thermal insulation system of the present invention includes an upper insulation member engageable with a lower insulation member to collectively surround and insulate a pipe. The ends of the upper and lower insulation members are preferably configured to form shiplap joints when the insulation members are wrapped around the pipe and connected together. In a preferred embodiment, the first end of the upper insulation member preferably has a projection that is dimensioned to fit into a groove in the first end of the lower insulation member to form a shiplap joint. Similarly, the second end of the lower insulation member has a projection that is dimensioned to fit into a groove in the second end of the upper insulation member forming a second shiplap joint. The projections on the first end of the upper insulation member and the second end of the lower insulation member preferably have a dome-shaped cross-section and extend across the entire length of the upper and lower insulation members. Correspondingly, the grooves in the second end of the upper insulation member and in the first end of the lower insulation member have a dome-shaped cross section to accommodate the respective projections.
The upper and lower insulation members are preferably made of a flexible foam material and, more preferably, made of TECHLITE(copyright), an open melamine foam. Foam material tends to fluctuate in size and shape depending on the environmental conditions. To compensate for the fluctuations in size and shape, relief cuts are made in the foam material to minimize the variance in the insulation. Specifically, a series of constant radius relief cuts are provided on the first and second ends of each of the insulation members. The cuts preferably extend from the ends of the insulation members toward the center portion. In a preferred embodiment, the radius of each of the cuts remains constant.
In addition to the constant radius relief cuts, radial relief cuts are made on the inner surface of the upper and lower insulation members. The cuts extend axially along the length of insulation members and radially advance from the inner surface toward the outer surface of each of the insulation members. In a preferred embodiment, three radial relief cuts are provided on each of the upper and lower insulation members. On each insulation member, one radial relief cut is preferably positioned at the center of the insulation member and the second and third radial relief cuts are provided on either side of the first radial relief cut, equidistant therefrom.
In a preferred embodiment of the present invention, the upper and lower insulation members are arc-shaped and the inner surface of the insulation members have variable radii of curvature. The radius of curvature at the center of the insulation members is preferably greater than the radius of curvature at the first and second ends of the insulation members such that a gap is created between the inner surface and the pipe at the center portion of each of the insulation member. The gap accommodates the variation in the size and shape of the insulation members resulting from varying environmental conditions. The various forms of relief cuts and gaps that accommodate size fluctuations allow the foam material of the insulation members to fluctuate while still preserving the connection at the shiplap joints of the insulation members and maintaining the fit of the insulation members around the pipe.
This invention, together with the additional features and advantages thereof, which was only summarized in the foregoing passages, will become more apparent to those of skill in the art upon reading the description of the preferred embodiments, which follows in the specification, taken together with the following drawings.


A pharmaceutical composition is disclosed comprising (A) and oligonucleotide having 5 to 50 nucleotide units, which is specifically hybridizable with DNA or RNA derived from a protein kinase C gene, entrapped in (B) sterically stabilized liposomes.

This invention relates to pharmaceutical compositions, particularly liposomal oligonucleotide compositions, their preparation and their use.
In WO 95/02069 there are described oligonucleotides specifically hybridizable with DNA or RNA derived from a protein kinase C (PKC) gene, which oligonucleotides are particularly for use in the diagnosis and treatment of neoplastic, hyperproliferative and inflammatory disorders associated with protein kinase C.
It has now been found that compositions retaining high activity after prolonged circulation in the bloodstream and exhibiting reduced accumulation of oligonucleotide in non-target organs such as the liver and kidney can be prepared by formulation of such oligonucleotides within sterically stabilised liposomes.
Accordingly, the present invention provides a pharmaceutical composition comprising (A) an oligonucleotide having 5 to 50 nucleotide units specifically hybridizable with DNA or RNA derived from a protein kinase C gene, entrapped in (B) sterically stabilised liposomes.
Hybridisation, in the context of nucleic acid chemistry, means hydrogen bonding, also known as Watson-Crick base pairing, between complementary bases, usually on opposite nucleic acid strands or two regions of a nucleic acid strand. Guanine and cytosine are examples of complementary bases which are known to form three hydrogen bonds between them. Adenine and thymine are examples of complementary bases which form two hydrogen bonds between them. xe2x80x9cSpecifically hybridizablexe2x80x9d and xe2x80x9ccomplementaryxe2x80x9d are terms which are used to indicate a sufficient degree of complementary such that stable and specific binding occurs between the DNA or RNA target and the oligonucleotide. It is understood that an oligonucleotide need not be 100% complementary to its target nucleic acid sequence to be specifically hybridizable.
An oligonucleotide is specifically hybridizable when binding of the oligonucleotide to the target interferes with the normal function of the target molecule to cause a loss of utility, and there is a sufficient degree of complementary to avoid non-specific binding of the oligonucleotide to non-target sequences under conditions in which specific binding is desired, i.e. under physiological conditions in the case of in vivo assays or therapeutic treatment, or, in the case of in vitro assays, under conditions in which the assays are conducted.
As used in the context of this invention, the term xe2x80x9coligonucleotidexe2x80x9d refers to a substance having a plurality of nucleotide units formed from naturally occurring bases and sugars joined by phosphodiester internucleoside (backbone) linkages. The term xe2x80x9coligonucleotidexe2x80x9d also includes analogues which function similarly to naturally occurring oligonucleotides but which have non-naturally occurring monomers (nucleotides) or portions thereof. These oligonucleotide analogues are often preferred over native forms because of properties such as enhanced cellular uptake, enhanced target binding affinity and increased stability in the presence of nucleases.
In preferred embodiments of the invention, the oligonucleotide (A) is specifically hybridizable with the translation initiation codon of the PKC gene, in which case it preferably comprises a CAT sequence, or with the 5xe2x80x2 untranslated region or 3xe2x80x2 untranslated region of the gene. In other preferred embodiments of the invention, the oligonucleotide (A) is specifically hybridizable with DNA or mRNA encoding a particular PKC isozyme (isoform) or a particular set of PKC isozymes.
The oligonucleotide (A) preferably comprises from 8 to 30 nucleotide units, more preferably 12 to 25 nucleotide units, especially 18 to 22 nucleotide units.
In some preferred oligonucleotides (A), at least one nucleotide is modified at the 2xe2x80x2 position of the sugar moiety. Certain preferred oligonucleotides (A) are chimeric oligonucleotides. xe2x80x9cChimeric oligonucleotidesxe2x80x9d or xe2x80x9cchimerasxe2x80x9d, in the context of this invention, are oligonucleotides which contain two or more chemically distinct regions, each made up of at least one nucleotide. These oligonucleotides typically contain at least one region of modified nucleotides that confers one or more beneficial properties (such as, for example, increased nuclease resistance, increased uptake into cells, increased binding affinity for the RNA target) and a region that is a substrate for RNase H cleavage. In one preferred embodiment, a chimeric oligonucleotide comprises at least one region modified to increase target binding affinity and, usually, a region that acts as a substrate for RNAse H. Affinity of an oligonucleotide for its target is routinely determined by measuring the Tm of an oligonucleotide/target pair, which is the temperature at which the oligonucleotide and target dissociate; dissociation is detected spectrophotometrically. The higher the Tm, the greater the affinity of the oligonucleotide for the target. In a more preferred embodiment, the region of the oligonucleotide which is modified to increase target binding affinity comprises at least one nucleotide modified at the 2xe2x80x2 position of the sugar, particularly a 2xe2x80x2-alkoxy, 2xe2x80x2-alkoxyalkoxy or 2xe2x80x2-fluoro-modified nucleotide. Such modifications are routinely incorporated into oligonucleotides and these oligonucleotides have been shown to have a higher Tm (i.e., higher target binding affinity) than 2xe2x80x2-deoxyoligonucleotides against a given target. In the chimeric oligonucleotides, the region which is a substrate for RNAse H comprises at least one 2xe2x80x2-deoxynucleotide. RNAse H is a cellular endonuclease that cleaves the RNA strand of RNA:DNA duplexes; activation of this enzyme therefore results in cleavage of the RNA target, and thus can greatly enhance the efficiency of antisense inhibition. Cleavage of the RNA target can be routinely demonstrated by gel electrophoresis. In another preferred embodiment, the chimeric oligonucleotide is also modified to enhance nuclease resistance. Cells contain a variety of exo- and endo-nucleases which can degrade nucleic acids. A number of nucleotide and nucleoside modifications have been shown to make the oligonucleotide into which they are incorporated more resistant to nuclease digestion than the native oligodeoxynucleotide. Nuclease resistance is routinely measured by incubating oligonucleotides with cellular extracts or isolated nuclease solutions and measuring the extent of intact oligonucleotide remaining over time, usually by gel electrophoresis. Oligonucleotides which have been modified to enhance their nuclease resistance survive intact for a longer time than unmodified oligonucleotides. A variety of oligonucleotide modifications have been demonstrated to enhance or confer nuclease resistance. Oligonucleotides which contain at least one phosphorothioate modification are presently more preferred. In some cases, oligonucleotide modifications which enhance target binding affinity are also, independently, able to enhance nuclease resistance.
Specific examples of some preferred oligonucleotides may contain phosphorothioate, phosphotriester, methyl phosphonate, short chain alkyl or cycloalkyl intersugar linkages or short chain heteroatomic or heterocyclic intersugar (xe2x80x9cbackbonexe2x80x9d) linkages, e.g. amide-type linkages. Most preferred are phosphorothioates and those with CH2xe2x80x94NHxe2x80x94Oxe2x80x94CH2, CH2xe2x80x94N(CH3)xe2x80x94Oxe2x80x94CH2, CH2xe2x80x94Oxe2x80x94N(CH3)xe2x80x94CH2, CH2xe2x80x94N(CH3)xe2x80x94N(CH3)xe2x80x94CH2 and Oxe2x80x94N(CH3)xe2x80x94CH2xe2x80x94CH2 and CH2xe2x80x94C(O)xe2x80x94NHxe2x80x94CH2 backbones (where phosphodiester is Oxe2x80x94Pxe2x80x94Oxe2x80x94CH2). Also preferred are oligonucleotides having morpholino backbone structures, for example as described in U.S. Pat. No. 5,034,506. In other preferred embodiments, such as the protein-nucleic acid or peptide-nucleic acid (PNA) backbone, the phosphodiester backbone of the oligonucleotide may be replaced with a polyamide backbone, the bases being bound directly or indirectly to the aza nitrogen atoms of the polyamide backbone, as described by P. E. Nielsen, M. Egholm, R. H. Berg, O. Buchardt, Science 1991, 254, 1497. Other preferred oligonucleotides may contain sugar moieties comprising one of the following at the 2xe2x80x2 position: OH; SH; SCH3; F; OCN; OCH2OCH3; O(CH2CH2)mOCH3 wherein m is 1, 2 or 3, preferably OCH2CH2OCH3; OCH2O(CH2)nCH3; O(CH2)nNH2 or O(CH2)nCH3 where n is from 1 to about 10; OCH2CH2NR1R2 wherein R1 and R2 are independently of each other, H or CH3. C1 to C10 lower alkyl, substituted lower alkyl, alkaryl or aralkyl; C1-10 lower alkoxy or substituted alkoxy, preferably OCH3; Cl; Br; CN; CF3; OCF3; Oxe2x80x94, Sxe2x80x94, or N-alkyl; Oxe2x80x94, Sxe2x80x94, or N-alkenyl; SOCH3; SO2CH3; ONO2; NO2; N3; NH2; heterocycloalkyl; heterocycloalkaryl; aminoalkylamino; polyalkylamino; substituted silyl; an RNA cleaving group; a cholesteryl group; a conjugate; a reporter group; an intercalator; a group for improving the pharmacokinetic properties of an oligonucleotide; or a group for improving the pharmacodynamic properties of an oligonucleotide and other substituents having similar properties. Oligonucleotides may also have sugar mimetics such as cyclobutyls in place of the pentofuranosyl group. Other preferred embodiments may include at least one modified base form or xe2x80x9cuniversal basexe2x80x9d such as inosine. Preferred bases includexanthine, hypoxanthine, adenine, 2-aminoadenine, guanine, 6-thioguanine, uracil, thymine, cytosine, 5-methylcytosine, 5-propynyluracil, 5-fluorouracil and 5-propynylcytosine.
In certain especially preferred embodiments of the invention, all nucleotides of the oligonucleotide (A) are 2xe2x80x2-deoxynucleotides and all backbone linkages are phosphorothioate linkages.
In certain other especially preferred embodiments, the oligonucleotide (A) is a chimeric oligonucleotide having one or more regions with 2xe2x80x2-deoxynucleotides and one or more regions with 2xe2x80x2-modified nucleotides, preferably 2xe2x80x2-alkoxynucleotides or 2xe2x80x2-alkoxyalkoxynucleotides, particularly 2xe2x80x2-methoxyethoxynucleotides, the one or more 2xe2x80x2-deoxynucleotide regions preferably having phosphorothioate backbone linkages and the one or more 2xe2x80x2-modified nucleotide regions preferably having phosphodiester or phosphorothioate backbone linkages. These chimeric oligonucleotides preferably comprise a region of 2xe2x80x2-deoxynucleotides between two regions of 2xe2x80x2-modified nucleotides, the deoxynucleotide region being preferably at least 4 nucleotides long, more preferably at least 6 nucleotides long, especially at least 8 nucleotides long.
The oligonucleotides used as component (A) of the composition of the invention may be conveniently and routinely made using well-known techniques such as solid phase synthesis. Equipment for such synthesis is available commercially from various sources including Applied Biosystems. The use of such techniques to prepare oligonucleotides such as the phosphorothioates and alkylated derivatives is well known. It is also well known to use similar techniques and commercially available modified amidites and controlled-pore glass (CPG) products such as biotin, fluorescein, acridine or psoralen-modified amidites and/or CPG (available from Glen Research, Sterling Va.) to synthesize fluorescently labelled, biotinylated or other modified oligonucleotides such as cholesterol-modified oligonucleotides.
Specific especially preferred oligonucleotides, for which the nucleotide sequences and preparation have been published in WO95/02069, include the following:
Most preferred among the oligonucleotides hereinbefore described are those having SEQUENCE ID No. 2,3 or 5.
In compositions of the invention, the oligonucleotide (A) is entrapped in sterically stablised liposomes (B). Examples of sterically stabilised liposomes are those in which part of the lipid is a glycolipid, particularly ganglioside GM, saturated phosphatidylinositol or galactocerebroside sulphate ester, such as those described in WO 88/04924; those in which part of the lipid is derivatised with hydrophilic polymer such as those described in WO 91/05545 or U.S. Pat. No. 5,225,212; and those comprising a vesicle-forming lipid and a lipid-polymer conjugate having a hydrophobic moiety and a polar head group, such as those described in WO 94/20073.
In a preferred embodiment of the invention, the liposomes (B) comprise at least one underivatised vesicle-forming lipid and at least one vesicle-forming lipid derivatised with hydrophilic polymer which may be, for example, a polymer containing a hydroxy and/or carboxyl group such as a polylactic acid, a polyglycolic acid or, preferably, a polyethylene-glycol. More preferably, the hydrophilic polymer is a polyethyleneglycol having a molecular weight of 1000 to 5000 daltons, such as 1500 to 2500 daltons, especially 1800 to 2200 daltons. The hydrophilic polymer is preferably derivatised with a polar head group of a phospholipid, especially a phospholipid having an amino head group, i.e. the derivatised lipid is preferably a phospholipid having an amino group, especially a phosphatidylethanolamine such as dilauroyl phosphatidylethanolamine, dimyristoyl phosphatidylethanolamine, dioleoyl phosphatidylethanolamine or, particularly, distearoyl phosphatidylethanolamine.
Various methods of derivatising an amino-containing lipid with a hydroxyl- and/or carboxyl-containing hydrophilic polymer will be apparent to those skilled in the art. Several such methods are described in WO 91/05545 and U.S. Pat. No. 5,225,212; the phospholipid having an amino group may be derivatised with the hydrophilic polymer by any of these methods. Preferably, the phospholipid having an amino group is derivatised with a hydroxyl-containing hydrophilic polymer such that the polymer is attached to the phospholipid through a carbamate linkage; this may be achieved by reacting a hydroxyl group of the polymer (other hydroxyl groups being capped, if necessary in view of their reactivity, for example by etherification) with diimidazole to give an activated imidazolexe2x80x94terminated polymer which is then reacted with the amino-containing phospholipid to couple the phospholipid to the hydrophilic polymer through a carbamate group, as described in WO 91/05545 or U.S. Pat. No. 5,225,212. In an especially preferred embodiment of the invention, the derivatised lipid is an amino-containing phospholipid, particularly a phosphatidylethanolamine, coupled through a carbamate group to a polyethyleneglycol capped at one end by an alkoxy group, particularly a methoxy or ethoxy group. Such a derivatised lipid is available commercially.
The derivatised lipid is generally present in a minor molar amount relative to the total lipid content of the liposomes, preferably in an amount of 1 to 20 mole % of the total lipid content, although a lower amount, for example 0.1 mole %, may be appropriate when the derivatised lipid has a high molecular weight. The major part of the lipid content of the liposomes generally comprises one or more underivatised vesicle-forming lipids such as are used in conventional liposomes. Such lipids include, for example, lipids having two hydrocarbon chains, usually in acyl groups, and a polar head group, including phospholipids, for example phosphatidylcholines such as dilauroyl phosphatidylcholine, dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoyl phosphatidylcholine, dioleoyl phosphatidylcholine, dilinoleoyl phosphatidylcholine, 1-palmitoyl-2-oleoyl phosphatidylcholine, phosphatidylethanolamines such as those mentioned hereinbefore, and phosphatidic acids such as dimyristoyl phosphatidic acid and dipalmitoyl phosphatidic acid. Other conventionally used lipids include sterols, particularly cholesterol, and glycolipids such as those mentioned hereinbefore. Preferably, the underivatised lipid comprises a mixture of a phospholipid, especially a phosphatidylcholine, and a sterol, especially cholesterol.
In the abovementioned preferred embodiment, the sterically stabilised liposomes (B) preferably comprise 4-10 mol % of the derivatised lipid, 40-80 mol % of the underivatised phospholipid and 20-50 mol % of the sterol. In especially preferred liposomes (B), the molar ratio of derivatised lipid: underivatised phospholipid: sterol is 1:10:5.
In another preferred embodiment of the invention, the liposomes (B) comprise (i) a glycolipid together with (ii) a vesicle-forming phospholipid or sphingolipid or mixture thereof and, optionally, (iii) a sterol and/or an acylglycerol lipid. The glycolipid is preferably a negatively charged glycolipid, especially ganglioside GM1 (monosialoganglioside) or hydrogenated phosphatidylinositol. The vesicle-forming phospholipid may be one or more of the phospholipids hereinbefore mentioned, preferably a phosphatidylcholine, a phosphatidylethanolamine or a mixture thereof. Especially preferred phospholipids are distearoyl phosphatidylcholine and dioleoyl phosphatidylethanolamine. The sphingolipid is preferably sphingomyelin and is preferably used together with a phospholipid. The sterol may be, for example, ergosterol or, preferably, cholesterol. The acylglycerol lipid may be an ester of glycerol containing two fatty acid acyl groups each having at least 12 carbon atoms, for example lauroyl, myristoyl, palmitoyl or oleoyl groups, and one acyl group of formula R1COxe2x80x94, where R1 is a residue, containing up to 10 carbon atoms, of a monocarboxylic acid of formula R1COOH after removal of the xe2x80x94COOH group or, preferably, of formula xe2x80x94COR2COOH where R2 is a residue, containing up to 10 carbon atoms, preferably 1 to 4 carbon atoms, of a dicarboxylic acid of formula HOOCxe2x80x94R2xe2x80x94COOH, especially succinic acid, after removal of both xe2x80x94COOH groups. An especially preferred acylglycerol is 1,2-dipalmitoyl-sn-3-succinylglycerol.
In this second preferred embodiment of the invention, the liposomes preferably comprise (i) a negatively charged glycolipid together with (ii) a vesicle-forming phospholipid and/or sphingolipid and (iii) a sterol or acylglycerol lipid, especially (i) ganglioside GM1 or hydrogenated phosphatidylinositol together with (ii) distearoyl phosphatidylcholine or dioleoyl phosphatidylethanolamine or a mixture thereof with sphingomyelin and (iii) cholesterol or 1,2-dipalmitoyl-sn-3-succinylglycerol.
The liposomes may comprise from 2 to 20 mol % of the glycolipid (i) and 80 to 98 mol % of (ii) the phospholipid, sphingolipid or mixture thereof. In preferred embodiments, where the liposomes also comprise a sterol or acylglycerol, they may comprise 2 to 20 mol %, preferably 4 to 10 mol %, of the glycolipid, 40 to 80 mol %, preferably 60 to 80 mol %, of the phospholipid, sphingolipid or mixture thereof and 10 to 50 mol %, preferably 20 to 40 mol %, of the sterol or 5 to 40 mol %, preferably 10 to 30 mol %, of the acylglycerol.
Specific especially preferred liposomes (B) are those described hereinafter in the Examples.
The oligonucleotide-containing liposomes of the invention can be prepared using known methods for the preparation of drug-containing liposomes. For example, in one method, the lipid composition is dissolved in an organic solvent, such as an alcohol, ether, halohydrocarbon or mixture thereof, the solvent is removed from the resulting solution, for example by rotary evaporation or freeze drying, and the resulting lipid film is hydrated by dispersing in an aqueous medium, such as phosphate-buffered saline or an aqueous solution of a sugar, e.g. lactose, which medium also contains the oligonucleotide (A), to give an aqueous suspension of liposomes in the form of multilamellar vesicles (MLV""s). The aqueous liposome suspension may be treated to reduce the liposome size, for example to give small unilamellar vesicles (SUV""s), using known methods, for example by sonication or by extrusion through one or more membranes, e.g. polycarbonate membranes, having a selected pore size. Liposomes according to the invention preferably have on average a particle size below 500 nm, more preferably 50 to 200 nm, especially 80 to 120 nm.
It is generally desirable to have as high a weight ratio of oligonucleotide to lipid as possible consistent with liposome stability. The maximum for this weight ratio may vary depending on the nature and composition of the lipid component, but in general this maximum is likely to be about 1:20. Ratios between 1:40 and 1:400 can be used with good results.
The invention includes a method of modulating the expression of protein kinase C in cells which comprises contacting the cells with a composition of the invention as hereinbefore defined. The invention also includes a method of treating a condition associated with expression of protein kinase C which comprises administering a composition of the invention as hereinbefore defined to a mammal, particularly a human, or cells thereof, in need of such treatment.
The composition of the invention may be administered by pulmonary delivery or, preferably, parenterally, for example intravenously, subcutaneously, intraperitoneally or intramuscularly. Conditions which may be treated with the composition include hyperproliferative disorders such as psoriasis and mammalian cancer, particularly human cancer such as lung cancer, breast cancer, colorectal cancer and skin cancer.
For these indications, the appropriate dosage will, of course, vary depending upon the method of administration and on the severity and responsiveness of the condition to be treated. Individual doses and the administration regime can best be determined by individual judgement of a particular case of illness. However, in general, satisfactory results in animals are indicated to be obtained at daily dosages from about 0.6 mg/kg to about 6 mg/kg.
In larger mammals, for example humans, an indicated daily dose in the range of about 4.2 mg to about 420 mg conveniently administered, for example in divided doses of up to 3 times per day.


This invention concerns a composition comprising a blend of polyolefin with the reaction of a functionalized polyolefin and polyetheramine in which the polyetheramine is grafted into the functionalized polyolefin in a customary mixing apparatus. A process for producing the reaction product of functionalized polypropylene and polyetheramine by melting with polypropylene in a customary mixing apparatus is also disclosed. Blends of the present invention are advantageously useful to prepare paintable automotive body parts. This invention further includes dyeable polyolefin compositions containing the reaction product of functionalized polyolefin and polyetheramine. Dyeable polyolefin fibers, including polypropylene fibers, are disclosed, which may be made by melt spinning, and which may be employed to make woven. and non-woven fabric.

This invention relates to a novel olefin polymer composed of the reaction of a functionalized polypropylene and a polyetheramine. This invention also relates to thermoplastic resin blends containing the novel olefin polymer and polypropylene. This invention also relates to dyeable compositions containing polypropylene and the reaction product of functionalized polypropylene and polyetheramine, wherein such compositions may be in the form of fibers.
While polypropylene has many other advantageous physical properties, its inherent ability to be dyed is very poor. Indeed, polypropylene has frequently been the ideal choice when a non-dyeable plastic is needed. For years there has been a long felt need for propylene compositions which are dyeable. Notwithstanding substantial efforts to provide dyeable polypropylene, this need remains unmet. This need is particularly acute in the fiber industry.
The most often used technique for obtaining colored polypropylene in fiber form is by addition of solid pigments to the polypropylene. Unfortunately, fibers with solid pigment are not nearly as vibrant as dyed fibers. Also, due to their limited number, pigments offer a significantly reduced spectrum of choices as compared to dyes. Likewise, use of pigments restricts the patterns that can be applied to an article of clothing prepared from polypropylene. Certain pigments, additionally, affect the drawability and final properties of the polypropylene fiber. Other polyolefins such as polyethylene possess similar disadvantages.
In view of the foregoing, it is apparent that a continuing need exists for dyeable polyolefin compositions, including polypropylene compositions.
This invention is a compound comprising a blend of polypropylene (xe2x80x9cPPxe2x80x9d) with the reaction product of a functionalized polypropylene and polyetheramine in which the polyether amine has grafted onto the functionalized polypropylene. By grafted it is meant that the amine functionality of the polyetheramine reacts with the anhydride component of the functionalized polypropylene to form a reaction product. For instance, a primary amine will react with a maleic anhydride to form an imide. This invention is also a process for producing the reaction product of the functionalized polypropylene and the polyether amine by melting with polypropylene in customary mixing apparatus such as an extruder. In this regard, the compound blend of this invention may be prepared by reactive extrusion by feeding a polyetheramine, a functionalized polypropylene, and polypropylene into an extruder at temperatures such that the polyetheramine reacts with the functionalized polypropylene to form a reaction product containing for example, an imide group.
In another respect, this invention is a composition comprising polypropylene, a cross-linked thermoplastic polyolefin vulcanizate, and the reaction product of a functionalized polypropylene and a polyether amine.
In one respect, the compositions of the present invention are useful for preparing molded automotive body parts, including directly paintable thermoplastic polyolefins (xe2x80x9cTPOxe2x80x9d) based, and thermoplastic polyolefin vulcanizates (xe2x80x9cTPVxe2x80x9d) based, automotive body parts.
In yet another respect, this invention is a dyeable composition, comprising: a polyolefin such as polypropylene and the reaction product of a functionalized polyolefin, such as maleated polypropylene, and a polyetheramine in an amount effective to increase the dyeability of the composition relative to polyolefin alone. In one embodiment of this invention, this composition is a fiber. As used herein, a xe2x80x9cfiberxe2x80x9d refers to a flexible, synthetic, macroscopically homogeneous body having a high ratio of length to width and being small in cross section. These fibers may be produced by any of the processes known in the art, including but not limited to direct profile extrusion, and slit or fibrillated tapes. Hence, it is further contemplated that the compositions of this invention are useful to in the preparation of dyeable fibers including dyeable woven and non-woven polyolefin fibers.
In still another respect, this invention is a process for preparing dyeable fibers, comprising: forming a dyeable composition comprising polyolefin and the reaction product of a functionalized polyolefin and a polyetheramine; and extruding the dyeable composition into fibers.
Applications of the fibers and filaments from the polyether modified polyolefins include, with limitation: woven garments (outerwear and underwear); carpeting; furniture and automobile upholstery, woven industrial fabrics; non-woven absorbents used in diapers, sanitary pads, incontinence pads, spill abatement, and medical absorbent pads; non-woven garments, including disposable medical garments; felts; pressed sheets; geo-textiles; filters (bipolar); packaging materials, including envelopes, and synthetic paper.
In addition, it is contemplated that the polyetheramines will improve the washability of a polyolefin-based textile fabric or non-woven mat. The nonpolar polyolefin tends to hold onto dirt due to the hydrophobic nature of both. The polyetheramine is expected to facilitate detergents to penetrate the fabric or matrix so the detergents can loosen and wash away the dirt and oils.
It is also contemplated that the incorporation of polyetheramines will increase the absorption and wickability of polyolefin textiles and non-wovens. One example is the melt blown, non-woven absorbent in baby diapers. Making the surface of the non-woven filament more hydrophilic by incorporating the polar polyetheramine into the polyolefin is expected to greatly increase the diaper""s moisture absorption characteristics.
It is also contemplated that the incorporation of polyetheramines will increase the abrasion resistance of fibers, fabrics, and other articles. Abrasion resistance is important in the drawing of formed fibers. Typically, a sizing is applied to reduce friction between the fiber and the metal surfaces of the drawing system.
It is also contemplated that the compositions are useful for making molded parts that contain filler such as glass. It is yet further contemplated that the compositions of the present invention may be useful in the preparation of films, including packaging films, to eliminate tie layers and to improve printability and barrier properties; and in packaging materials for electronics components such as circuit boards or semiconductor chips, wherein the packaging materials may provide electrostatic dissipation which would thereby protect the components from damage. It is yet further contemplated that the composition of the present invention may be useful to improve the barrier properties for polyethylene and to modify polyethylene as a tie layer in multi-layer films. It is further contemplated that the composition of the present invention may be useful as an additive as polypropylene based reinforcement fibers for concrete. Also, it is contemplated that this invention may be useful for extended coatings for metal or glass substrates, with improved printability and metal, and as packaging films with improved adhesion to metallized layer.
It is yet further contemplated that the composition of the present invention may be useful for dyeable ribbon, paintable foams, antistatic foams, adhesive bondable PP components, and improved substrates for electroplating, such as for electromagnetic interference shielding or decoration.
The present invention provides a solution to one or more of the disadvantages and needs discussed above. In this regard, this invention surprisingly provides a dyeable polyolefin is composition that possesses good tensile strength and processability. It is further expected that this invention provides a polyolefin composition which unexpectedly and advantageously has additional improved properties, including one or more improved properties such as washability, wetability, static retention, bondability to materials such as carpet backings, and flammability.
Plastics are increasingly being employed in the production of motor vehicles. Impact modified polypropylene has proved to be particularly suitable for applications such as bumpers, spoilers, fenders, side bump strips and the like. Therefore, a thermoplastic resin blend having the improved properties of the instant invention has significant potential commercial usefulness. These resin compositions, according to the present invention, are useful as engineering plastics which are materials for structural members in the fields of transport machines (automobiles, ships and the like), apparatus, tools, electronic appliances, electric appliances, sporting goods, leisure goods and the like; and for connectors, tubes and the like.
The blend of polypropylene with the reaction product of maleated polypropylene and polyether amine shows improved paintability, improved impact resistance, and excellent mold flowability over blends of polypropylene and maleated polypropylene.
Moreover, polyolefins have been and will continue to be used in the production of fibers and fabrics made therefrom. However, polyolefins are inherently not susceptible to being dyed. A need exists, therefore, for dyeable polyolefins. The blend of polyolefin with the reaction product of a functionalized polyolefin and a polyetheramine provides a solution to this problem. Suitable thermoplastic resin compositions useful in the manufacture of fibers and non-wovens should contain an effective amount of polyetheramine to enhance the dyeability of the composition relative to compositions containing polypropylene alone, or containing only polypropylene and functionalized polypropylene such as maleated polypropylene.
In one embodiment of the present invention, the thermoplastic resin composition may contain up to about 12% by weight polyetheramine and up to about 30% by weight functionalized polyolefin. In particular, the thermoplastic resin composition may contain up to about 8% by weight polyetheramine and up to 20% by weight functionalized polyolefin. In a preferred embodiment, the thermoplastic resin composition may contain from about 0.1 to about 5% by weight polyetheramine and from about 0.2 to about 15% by weight functionalized polyolefin. In an especially preferred embodiment, the thermoplastic resin composition may contain from about 1 to about 4% by weight polyetheramine and from about 2 to about 12% by weight functionalized polyolefin.
The composition containing polyolefin and the reaction product of functionalized polyolefin and polyetheramine may be further blended with other materials used in making fibers for a variety of end users. For example, the composition can be blended with other polymers such as polyester and polyamide (nylon).
Polyolefins used in this invention are well known. Generally, any polyolefin may be employed in the practice of this invention that can be used to make plastic parts, fibers, and the like as described herein. In general, the polyolefins employed in the practice of this invention have a melt flow index in the range from about 0.7 to about 1500. Representative polyolefins include polypropylene and polyethylene. Polyethylene is a well known material. Polyethylene employed in the practice of this invention can be made by traditional Ziegler-Natta catalysts, metallocene catalysts, or single site geometry catalysts, the latter two being available from Exxon Chemical and The Dow Chemical Company, respectively. Such polyolefins may have other monomers included in the polymers, such as propylene, butylene, and octene. Polypropylenes, likewise, are known from polymer chemistry as are described, for example, in Kunststoff-Handbuch, Volume IV, Polyolefins, edited by R. Vieweg, A. Schley and A. Schwarz. Carol Hanser Verlag, Munich, 1969, and are commercially available, so that no details need be given.
One such commercially available polypropylene is available from Amoco Chemical under the name AMOCO 1016 polypropylene.
Functionalized polyolefin is a polyolefin onto which a monomer has been grafted. Any functionalized polyolefin can be employed in the practice of this invention which may react with the polyetheramine and which is generally compatible with a given polyolefin after reaction with the polyetheramine. The usual method of such grafting is by free radical reaction. In the practice of this invention, the functionalized polyolefin is not a copolymer of. for example, maleic anhydride and propylene, where the maleic anhydride moiety is predominantly in the backbone of the copolymer. Representative examples of polyolefins to which a monomer has been grafted include homopolymers and copolymers of various olefins such as ethylene, propylene, butylene, pentene, hexylene, heptene, and octene. Suitable monomers for preparing functionalized polyolefin are, for example, olefinically unsaturated monocarboxylic acids of less than 12 carbon atoms, e.g., acrylic acid or methacrylic acid, and the corresponding tert-butyl esters, e.g., tert-butyl (meth)acrylate, olefinically unsaturated dicarboxylic acids of less than 12 carbon atoms, e.g., fumaric acid, maleic acid, and itaconic acid and the corresponding mono-and/or di-tert-butyl esters, e.g., mono- or di-tert-butyl fumarate and mono- or di-tert-butyl maleate, olefinically unsaturated dicarboxylic anhydrides of less than 12 carbon atoms, e.g., maleic anhydride, sulfo- or sulfonyl-containing olefinically unsaturated monomers of less than 12 carbon atoms, e.g., p-styrenesulfonic acid, 2-(meth)acrylamide-2-methylpropenesulfonic acid or 2-sulfonyl (meth)acrylate, oxazolinyl-containing olefinically unsaturated monomers of less than 12 carbon atoms, e.g., vinyloxazolines and vinyloxazoline derivatives, and epoxy-containing olefinically unsaturated monomers of less than 12 carbon atoms, e.g., glycidyl (meth)acrylate or allyl glycidyl ether. The most preferred monomer for preparing functionalized polyolefin is maleic anhydride. The most preferred polyolefin is polypropylene. Hence, the most preferred functionalized polypropylene is maleated polypropylene. Maleated polypropylene is well known, being manufactured by a number of producers. For example, maleated polypropylene is available from Eastman Chemical under the name EPOLENE E-43.
The functionalized polyolefin used in the practice of this invention may have a wide variety of number average molecular weights. In the practice of this invention, any functionalized polyolefin can be used which reacts with polyetheramines afford a polyolefin fiber that has improved dyeability to both polyolefin alone and a polypropylene functionalized polyolefin blend. When the functionalized polyolefin is used to make dyeable compositions such as used to make fibers, the functionalized polyolefin may have a number of average molecular weight greater than about 3,000 and preferably less than about 50,000. Within this range it is contemplated that certain ranges of molecular weights will yield compositions having the highest dyeability, depending on amounts and type of polyolefin, polyetheramine, as well as other considerations such as processing conditions, spinnability of fibers, and other desired physical properties of the resulting dyeable composition. Thus, in certain embodiments it is expected that lower molecular weight functionalized polyolefin may have superior benefits such as those having number average molecular weights below 10,000 or 20,000. In other contexts, higher molecular weight materials may prove to be more advantageous.
It should be appreciated that the polyolefin can be bonded to one or two monomers when the polyolefin is linear, while more than two monomers might be included when the polyolefin is branched. Typically, one or two monomers are present.
The polyetheramines used in this invention include monoamines, diamines and triamines, having a molecular weight of from about 150 to about 12,000, such chemicals including but not limited to hydroxyl, amine, and aminoalcohol functionalized polyether materials. Preferred polyetheramines have a molecular weight of from about 1,000 to about 3,000. Suitable monoamines include JEFFAMINE(trademark) M-1000, JEFFAMINE(trademark) M-2070, and JEFFAMINE(trademark) M-2005. Suitable diamines include JEFFAMINE(trademark) ED-6000, JEFFAMINE(trademark) ED-4000, JEFFAMINE(trademark) ED-2001 including XTJ-502 and TXJ-418, JEFFAMINE(trademark) D-2000, JEFFAMINE(trademark) D-4000, JEFFAMINE(trademark) ED-900, JEFFAMINE(trademark) ED-600, and JEFFAMINE(trademark) D-400. Suitable triamines include JEFFAMINE(trademark) ET-3000, JEFFAMINE(trademark) T-3000 and JEFFAMINE(trademark) T-5000. Preferred polyetheramines include JEFFAMINE(trademark) M-2070 and JEFFAMINE(trademark) ED-2001. See the glossary for structures of these polyetheramines. More preferred polyetheramines of the present invention have a molecular weight in the range from about 1500 to about 2000. One especially preferred polyetheramine is a polyether monoamine which contains from about 36 to about 44 ethylene oxide units and from I to about 6 propylene oxide units. In one embodiment, such polyether monoamines have a molecular weight in the range from about 2000 to about 2200. In another embodiment, the polyether monoamine contains about 40 to about 43 ethylene oxide units and from about 2.4 to about 3 propylene oxide units. Certain polyether monoamines are of formula:
wherein m is about 36 to about 44 and wherein n is about 1 to about 6, including polyether monoamines wherein m is about 40 to about 43 and n is about 2.4 to about 3, as well as compounds of the formula having a molecular weight of about 2000 to about 2200.
In the practice of this invention, monoamines and diamines are preferred. Suitable polyether blocks of the polyetheramine include polyethylene glycol, polypropylene glycol, copolymers of polyethylene glycol and polypropylene glycol, poly(1,2-butylene glycol), and poly(tetramethylene glycol). The glycols can be aminated using well known methods to produce the polyetheramines. Generally, the glycols are prepared from ethylene oxide, propylene oxide or combination thereof using well known methods such as by a methoxy or hydroxy initiated reaction. When both ethylene oxide and propylene oxide are used, the oxides can be reacted simultaneously when a random polyether is desired, or reacted sequentially when a block polyether is desired.
In one embodiment of the present invention, the polyetheramines are prepared form ethylene oxide, propylene oxide or combinations thereof. Generally, when the polyetheramine is prepared from ethylene oxide, propylene oxide or combinations thereof, the amount of ethylene oxide on a molar basis is greater than about 50 percent of the polyetheramine, preferably greater than about 75 percent and more preferably greater than about 90 percent. In one embodiment of this invention, polyols and amines including polyalkylene polyamines and alkanol amines or any amine that is not a polyetheramine is disclosed herein may be absent from the composition. Similarly, functional groups other than ether linkages and amine groups may be absent from the polyetheramine. The polyether amines used in the practice of this invention can be prepared using well known amination techniques such as described in U.S. Pat. No. 3,654,370; U.S. Pat. No. 4,152,353; U.S. Pat. No. 4,618,717; U.S. Pat. No. 4,766,245; U.S. Pat. No. 4,960,942; U.S. Pat. No. 4,973,761; U.S. Pat. No. 5,003,107; U.S. Pat. No. 5,352,835; U.S. Pat. No. 5,422,042; and U.S. Pat. No. 5,457,147. Generally, the polyether amines are made by aminating a polyol, such as a polyether polyol with ammonia in the presence of a catalyst such as a nickel containing catalyst such as a Ni/Cu/Cr catalyst.
The mixing of the functionalized polyolefin and polyetheramine and optionally also polyolefin may be carried out in a customary mixing apparatus including batch mixers, continuous mixers, kneaders, and extruders. For most applications, the mixing apparatus will be an extruder.
The dyeable composition of this invention may be formed into fibers by any number of known methods. Thus, conventional techniques to prepare fibers can be employed, including melt spinning, dry spinning, and wet spinning. As used herein, xe2x80x9cspinningxe2x80x9d refers to the overall process of polymer dissolution or melting, extrusion, and fiber formation. For example, in melt spinning the dyeable composition described above in molten form is forced through a spinneret (a die) as is used in the art. Size and shape of the spinneret may vary depending on desired denier of the final fiber. The thin jets emerging from the holes in the spinneret are cooled (as by an air quench) to solidify the polymeric composition. Melt spinning is typically conducted at high temperatures such as from 240-310xc2x0 C. In dry spinning, the dyeable composition is dissolved in a suitable solvent, and the solution is extruded under pressure through a spinneret. The emerging jet from the spinneret is heated to drive off solvent, thereby producing a solid fiber. In wet spinning, the polymer is also dissolved in a solvent, which is forced under pressure through a spinneret which is submerged in a coagulation bath, which causes precipitation of the emerging jet of extruded material.
The filaments exiting the spinneret holes are generally subjected to an air quench, with the filaments being taken up by devices that attenuate the spinline to the desired linear density. These devices collect the spun yarn in a suitable form for further processing. A godet wheel is commonly employed to control take-up velocity, which for example is typically 10-33 meters/second for fine yarns. The yarn may be stacked in cans, taken up in bobbins, or directly transferred to drawing and/or texturizing equipment.
The filaments resulting from the melt, dry, or wet spinning process are generally subjected to one or more drawing operations. Thus, the filaments are drawn to achieve an irreversible expansion, thereby inducing molecular orientation with respect to the fiber axis and thereby developing a fiber fine structure. The drawing of polyolefin fibers typically increases orientation and further modifies physical properties of the fiber. Linear density may thus be conveniently reduced during drawing. Drawing can be accomplished in-line with spinning equipment in a conventional, continuous spin-draw process, or in a second processing step. Current melt spinning devices often provide both spinning (extrusion) and drawing in a single high speed process. Likewise, bi-component fibers can be made in side-by-side or skin/core configurations using known apparatus.
The resulting fiber may optionally be modified by texturing, such as by thermochemical annealing. Texturing also provides bulk and softness to articles of manufacture made from the fibers. The fibers can be further processed using known techniques to form yarns having a desired degree of twist to facilitate interfilament cohesion. Similarly, known methods can be employed to disrupt filament alignment and parallelization of continuous filament synthetic fibers to produce yarns generally associated with spun fibers.
The yarn can be manipulated using conventional techniques by weaving or knitting processes to form woven fabric. Additionally, conventional techniques can be employed to produce non-woven fabrics in which the fibers have been bonded chemically, mechanically interlocked, or both. For instance, staple length fibers may be dispersed in a fluid (liquid in wet-laid non-wovens or air for air-laid non-wovens, depending on the technique chosen) and deposited in sheet-like planar form on a support base prior to bonding or interlocking.
The size of the fiber will depend on the end use. For instance, heavier fibers are often employed for carpet backing as opposed to fibers used to make clothing apparel and the like. Later, optionally after additional processing steps such as application of a spin finish, the fibers are drawn.
Conventional methods can be employed to dye the fibers of this invention. For instance, the fibers may be dyed in a dye both using conventional dyes and disperse dye techniques. Generally, the dye is applied in the form of a dye solution so that it can be readily applied by dipping the fiber through a trough, for example, containing the dye solution, or by spraying the dye solution on the fiber, or by using a cascading roll technique. As is common, the dye solution can be in the form of a print paste, from which the dyeing is typically conducted by roller printing or screen printing. The fibers can be dyed multiple times using one or more dyeing techniques.
Aqueous dye baths typically have a pH of from about 2 to about 11, generally between about 2 to about 6 for acid dyes. The pH may be adjusted if desired using a variety of compounds, such as formic acid, acetic acid, sulfamic acid, citric acid, phosphoric acid, nitric acid, sulfuric acid, monosodium phosphate, tetrasodium phosphate, trisodium phosphate, ammonium hydroxide, sodium hydroxide, and combinations thereof. Use of a surfactant can be used to aid in dispersing sparingly water soluble disperse dyes in the dye baths. Typically, nonionic surfactants can be employed for this purpose. During the dying step, the dye bath may be agitated to hasten the dyeing ratio. The dyeing step can be carried out at a variety of temperatures, with higher temperatures generally promoting the rate of dyeing.
Another technique known in the art is jet dyeing, which permits high-temperature dyeing and impingement of the dye onto the moving fabric through use of a venturi jet system. Carriers permit faster dyeing at atmospheric pressure and below 100xc2x0 C. The carriers are typically organic compounds that can be emulsified in water and that affinity for the fiber. Representative examples of such carriers include aromatic hydrocarbons such as diphenyl and methylnaphthalene, phenols such as phenylphenol, chlorinated hydrocarbons such as dichloro- and tricolor- benzene, and aromatic esters such as methyl salicylate, butyl benzoate, diethylphthalate, and benzaldehyde. Carriers are generally removed after dyeing.
Subsequent to dyeing, using a dye mixture with additives above, dry heat may be applied to the fibers at a wide range of elevated temperatures to cause the dye to penetrate into, and become fixed in, the fiber. The dye fixation step involves exposing the fiber to dry heat, such as in an oven. The temperature can vary up to the melt or glass transition temperature of the composition fiber. Generally, higher drying temperatures result in shorter drying times. Typically, the heating time is from about 1 minute to about 10 minutes. Residual dye may then be removed from the fibers.
A disperse dye mixture may thus be applied to the polypropylene fibers in various ways. The dye mixture may be applied intermittently along the length of yarn formed from fibers using various well known techniques to create a desired effect. One suitable method of dyeing fibers may be referred to as the xe2x80x9cknit-deknitxe2x80x9d dyeing technique. According to this method, the fibers are formed into a yarn which in turn is knit, typically into a tubing configuration. The dye mixture is then intermittently applied to the knit tubing. After dyeing, the tubing is unraveled and the yarn thus has an intermittent pattern. According to an alternative printing method, the fibers are first formed into yarn which is then woven or knitted into fabric, or is tufted into the carpet. A conventional flat screen printing machine may be used for applying the dye mixture to the fabric or carpet.
Continuous dyeing is carried out on a dyeing range where fabric or carpet is continuously passed through a dye solution of sufficient length to achieve initial dye penetration. Some disperse dyes may be sublimated under heat and partial vacuum into polymer fiber by methods known in the art. Printing of polyolefin compositions made in accordance with this invention can be accomplished with disperse dyes by heat transfer printing under pressure with sufficient heating to cause diffusion or disperse dyes into the polyolefin. Block, flat screen, and heat transfer. batch processes, and engraved roller and rotary screen printing continuous processes may be used. Different dye solutions may be jet-sprayed in programmed sequence onto fabric or carpet made of the compositions of this invention as the fabric passes under the jets to form patterns. Dye solution may be metered and broken or cut into a pattern of drops that are allowed to drop on a dyed carpet passing underneath to give a diffuse over-dyed pattern on the carpet. Competitive dyeing of polyolefins is useful when dyeing styled carpets consisting of several different fibers such as nylon, polyester,. etc., and a polyolefin. Different styling effects can be produced by controlling shade depth on each type of fiber present. Acid, disperse and premetallized dyes, or combinations thereof, depending upon the fibers present, can be employed to obtain styling effects. It may be possible to produce tweed effects by controlling the amount of reaction product and/or polyetheramine in the dyeable composition. Print dyeing, space dyeing, and continuous dyeing can be carried out with fabrics made from such yarns.
There are many commercially available disperse dyes. Dyes are classified based on method of application and, to a lesser extent, on chemical constitution by the Society of Dyers and Colorists. Various disperse dyes may be found in the listing xe2x80x9cDyes and Pigments by Color Index and Generic Namesxe2x80x9d set forth in Textile Chemist and Colorist, July 1992, Vol. 24, No. 7, a publication of the American Association of Textile Chemists and Colorists.
Dyes are intensely colored substances used for the coloration of various substrates, such as paper, plastics, or textile materials. It is believed that dyes are retained in these substrates by physical absorption, by salt or metal-complex formation, or by the formation of covalent chemical bonds. The methods used for the application of dyes to the substrate differ widely, depending upon the substrate and class of dye. It is by applications methods, rather than by chemical constitutions, that dyes are differentiated from pigments. During the application process, dyes lose their crystal structures by dissolution or vaporization. The crystal structures may in some cases be regained during a later stage of the dyeing process. Pigments, on the other hand, retain their crystal or particulate form throughout the entire application procedure.
A large number of dyes, with widely differing properties, are therefore necessary because of the great variety of materials to be dyed. On a worldwide basis, it is believed that several thousand different dyes have achieved commercial significance. Generally, dyes have been classified into groups two ways. One method of classification is by chemical constitution in which the dyes are grouped according to the chromophore or color giving unit of the molecule. A second method of classification is based on the application class of end-use of the dye. The dual classification system used in the color index (CI) is accepted internationally throughout the dye-manufacturing and dye-using industries. In this system, dyes are grouped according to chemical class with a CI number for each chemical compound and according to usage or application class with a CI name for each dye. Disperse dyes are generally water-insoluble nonionic dyes typically used for dyeing hydrophilic fibers from aqueous dispersion. Disperse dyes have been used on polyester, nylon, and acetate fibers.
A number of spin finishes can be applied to the fibers prior to drawing. Such finishes can be water-based. The spin finishes can be anionic or nonionic, as is well known in the art. Also, the fibers can be finished prior to dyeing, as by texturizing through mechanical crimping or forming, as is well known in the art.
In addition, additives commonly used in this art may be optionally incorporated into the dyeable composition and or fibers. Representative examples of such materials include hydrophilic modifiers such as monoglyceride such as glycerol monostearate, long chain hydrocarbon with hydrophilic groups appended such as a potassium or sodium salt of a linear alkyl phosphate, or combination thereof. The hydrophilic groups may be carboxylates, sulfates, sulfonates, phosphates, phosphonates, as well as quaternary ammonium salts and polyether groups. In addition, swelling agents can be used during dyeing, wetting agent, dye compatibilizers, thickening agents such as various gums. Since polyolefin fibers are often used in outdoor applications, such as outdoor carpeting, the addition of UV stabilizers may be added. Also, antioxidants may be added to the compositions.
Besides the PP/functionalized-PP/polyetheramine structural components according to the invention, the resin compositions may, to improve the impact strength, contain impact modifiers, advantageously impact-modifying elastomers in applications such as for bumper fascias. Impact-modifying elastomers potentially useful for the instant invention are known to a skilled worker. Examples are rubbers based on ethylene, propylene, butadiene, and acrylates, e.g., methacrylates, or mixtures thereof. Other examples include EP and EPDM rubbers, with EP rubber (ethylene propylene rubber) being preferred in applications where automotive body parts are being prepared. A representative example of a currently commercially available EP rubber is sold under the name VISTALON 878 by Exxon Chemical.
Impact-modifying elastomers are described for example in Methoden der organischen Chemie (Houben-Weyl), Volume XIV/1, Makromolekulare Chemie (Georg-Thieme-Verlag, Stuttgart, 1961), pages 390 to 406, and in the monograph by C. B. Bucknal, Toughened Plastics (Applied Publishers, London, 1977).
A composition containing polypropylene and elastomers, such as EP rubber, is commonly referred to as a xe2x80x9cTPO,xe2x80x9d which stands for thermoplastic polyolefin. TPO""s are commonly used in the manufacture of molded automotive body parts, such as bumper fascias. Such molded parts may also contain other components such as fillers, as described hereinbelow. TPO-based compositions can be prepared in the same manner as for non-elastomer-containing compositions. TPO""s are commonly sold in compound or reactor grades. Representative examples of TPO include those available from Himont under the names HIMONT CA53A and HIMONT LB 15016, and from D and S Plastics International under the name DEXFLEX D-161.
A composition containing polypropylene and vulcanized elastomers (vulcanized rubber), including thermoplastic polyolefin vulcanizates, is commonly referred to as a xe2x80x9cTPV.xe2x80x9d TPV""s are commonly used in the manufacture of molded automotive body parts, such as grips and handles. These molded parts may contain other components such as fillers, as described below. TPV-based compositions may be prepared in the same manner as for non-elastomer-containing compositions.
It is contemplated that the polyetheramine and functionalized propylene, and optionally a small amount of PP, TPV, or TPO, can be reacted to form a reaction product concentrate and, later, the reaction product concentrate can be blended with polypropylene or TPO or TPV. In this aspect of the invention, the polyetheramine comprises from about 10 to about 50 weight percent of the concentrate. When the reaction product of polyether amine and maleated PP is prepared neat, the reaction product can be blended or compounded with polypropylene or TPO and any other components of the desired compositions to the desired levels using a mixing apparatus such as an extruder. It should be understood that PP may be commonly used to dilute the reaction. Depending on the type of mixer, the reaction product, polypropylene and any other components can be thoroughly mixed as solids prior to introducing the admixture in the mixing apparatus. Alternatively, mixers are available which will mix the components during operation. In either case, during operation of the mixer, the components are heated to melt the solids, with the melted components being thereafter mixed to form the final composition.
In addition to the structural components of polyolefin, functionalized polyolefin, and polyetheramine and any impact modifier contained in a resin compositions according to the instant invention, the resin may also contain reinforcing agents and/or additives. The reinforcing agents used may be reinforcing fillers, for example, carbon or carbon fibers; clay, chalk, talc, and mica to control shrinkage and control coefficient of thermal expansion; glass (beads, fibers or mats such as of woven fibers) to increase stiffness; and pigments. Further, the fillers may be finished with adhesion promoters and/or sizing agents. In addition, phosphite or hindered phenol or both can be added as a stabilizer (as a free radical scavenger).
When compositions include glass beads or fibers, the composition can contain up to about 40% glass filler if highly stiff compositions are desired. When compositions include glass mats, the composition can contain up to about 80% glass. More typically, from about 2% to about 10% glass filler in the compositions is employed. Advantageously, the compositions of the present invention that contain glass filler generally are substantially free of voids that typically develop in compositions containing polypropylene and glass. While not wishing to be bound by theory, it is believed that the reaction product of polyetheramine and maleated polypropylene serves to xe2x80x9cwetxe2x80x9d the glass to thereby make the glass and polypropylene more combinable (more miscible). In this aspect of the invention, it is preferred to employ maleated polypropylene having an average molecular weight of about 40,000 to about 60,000, as is described hereinabove. Generally, glass filler and polypropylene are not miscible, and their combination commonly leads to voids in the resulting compositions. The relatively higher molecular weight materials xe2x80x9cwetxe2x80x9d the glass to make the glass filler particles and polypropylene more combinable to thereby decrease the amount of voids in the resulting compositions.
Suitable thermoplastic resin compositions for use in applications such as for automotive bumper fascias may contain from about 66 to about 80 wt % TPO or TPV, from about 5 to about 30 wt % maleated PP and from about 2 to about 10 wt % polyetheramine. When the compositions include elastomers, such as in TPO-based compositions used to make automotive body parts, or TPV based compositions, the compositions generally comprise from about 5 to about 40% wt maleated TPO or TPV, from about 2 to about 10 wt % polyetheramine and from about 50 to about 93 wt % PP, such as percentages based on the weights of these components of the composition. Preferred compositions that include elastomers, or which are TPV-based, comprise about 15 to about 30 wt % maleated PP, from about 2 to about 8 wt % polyetheramine and from about 62 to about 83 wt % TPO or TPV.
The preferred customary mixing apparatus is an extruder in which the polyetherarmine is grafted onto the functionalized polyolefin at from about 175 to 300xc2x0 C. in the course of a residence time of from about 25 to 300 seconds. For typical compositions of this invention, degradation begins to occur above this temperature range and below this range the compositions generally do not melt. Polypropylene is a non-reactive component of the mixing blend. The preferred temperature range is from about 190 to 260xc2x0 C. Excess moisture in the blended compositions may cause surface blemishes upon molding, but the moisture can be removed by the normal drying processes, including the use of heated, dry air.
Molded articles prepared from compositions according to the present invention, aside from dyeable compositions and fibers, are generally directly paintable. Representative examples of paints commonly employed for this purpose include urethane-based and melamine-based paints. Such paints may be applied using conventional techniques. Advantageously, compositions of the present invention may be painted directly without solvent borne chlorinated polyethylene pretreatment and optionally without primer, though a primer may be used.
In the examples, continuous compounding is carried out in a Werner and Pfleiderer 30 mm twin screw extruder (ZSK30), having a nine barrel configuration, three kneading zones and one vent section, in which the feed sequence was a combined feed in which all the components fed at the same location (hopper of the extruder).

Dyeable polyolefin containing polyetheramine modified functionalized polyolefin