A tool for installation and removal of power transmission belts from fixed center pulleys in a power transmission system. The tool consists of a principal member for attaching to a pulley, thus absorbing forces created during installing and removing belts, and simplifying the process. Separate installing and removing devices are secured to the principal member and all configured to support and maneuver the belt while installing onto, or removing from, the selected pulley.

1. Field of the Invention
This invention relates to a tool for installing and removing power transmission belts from fixed center pulleys. It is particularly directed to continuous belts having an inner multi-rib construction adapted to engage pulleys which have a matching set of V-grooves. A typical v-ribbed belt system is shown, for example in Fisher et al., U.S. Pat. No. 3,951,006. In this system, pulleys are coupled to the engine drive shaft and to such accessory drives as the alternator, water pump, power steering pump, or air conditioning compressor. The belt is operated over the drive shaft pulley and drives the accessories provided in the system. Although the above referenced patent also utilizes a tensioner applied to the outer surface of the belt, such a device is not always required. The term xe2x80x9cmulti-ribxe2x80x9d is understood to mean a belt having its inner drive surface formed of a plurality of V-shaped or trapezoidal members shaped driving members designed to inter-fit with associated pulley grooves.
Tools of this type are necessary to install the belt over the various pulleys in the system, and also to remove the belt, and must be capable of accomplishing this with minimum effort and damage to the belt. The tool may also be used to test special accessory drive configurations, such as during a routine hot test after engine assembly. For example, it may be desired to test a water pump, in which case only the water pump is installed and the tool is applied only to the pulley which is attached to this pump.
2. Prior Art Statement
It is been known to utilize simple hand tools for the purpose of installing a conventional power transmission V-belt having a single trapezoidal drive section. This is done by the use of a wedging tool such as shown in Engard et al., U.S. Pat. No. 2,470,810 and Hawkins, U.S. Pat. No. 2,621,529. A variation of these wedging devices is shown in Simmons et al., U.S. Pat. No. 2,505,216 wherein a tool having a curved cam surface is used to permit the single section belt to slide over this surface onto the pulley.
It is an entirely different problem to install a multi-rib belt, however, and one such device is shown in Winninger, et al., U.S. Pat. No. 6,033,331, wherein a similar wedging tool is used to position a multi-rib belt onto a pulley. In all of the above patents the tool is not secured to any member of the drive system, and must be operated without any support, making the operation more difficult.
The present invention is an improvement over the prior art and provides for a tool which has a principal member to be mounted directly on one of the accessory drive pulleys and secured thereto, thereby providing a secure support for the tool. This makes it easier to operate and to control the belt. The principal member has a plurality of circular openings for insertion of either an installing device which allows the belt to be stretched and installed on the selected pulley; or a removal device which enables a belt to be stretched and removed from the pulley. The principal member also comprises a control member, such as a pair of handles, which are used to rotate and manipulate the principal member into the desired installing and removal positions of the belt. To install the belt around the pulleys, the installing device is first inserted into one of the circular openings by utilizing an integral pin on the device. This is inserted into whichever of the openings that provides clearance in the drive system. At the same time, other members will lock the installing tool in place so that it will not fall out. The principal member has an external cylindrical shaft which is inserted into the inner circular opening of the pulley. In order to lock the cylindrical shaft in place within the pulley, a bolt in the principal member is tightened, this bolt being connected via a wedging nut to locking members within the surface of the principal member. This rotation expands the locking members to lock them in place within the pulley. The belt is placed loosely around the other pulleys in the drive, then around the installing tool surface, which is designed with a curved cam configuration. At this point the belt is located outwardly of the pulley flanges.
The handles are rotated and manipulated so that the belt is slid over the ramp surface of the installing tool and onto the belt-engaging surface of the pulley. The ramp provides support to the inner surface of the belt, while simultaneously wrapping the belt around the installation pulley. This insures inter-engagement of the ribs of the belt and the grooves of the pulley. The tool is then disengaged by loosening the bolt to release the locking members which will then no longer be locked within the inner pulley surface. The power transmission system is then in condition for operation.
The removal of the belt is accomplished by placing the belt removal attachment in the same manner as the installing device. This device also has an integral cylindrical pin which is inserted into one of the circular openings in the principal member. This device has a belt-supporting surface which is similar to that of the installing device, with a concave surface acting as a cam or ramp. The configuration of this surface is slightly different than that of the installing device, in order to facilitate removal of the belt. To remove the belt, the principal member is again placed within the pulley, and the bolt is tightened to lock the principal member with the pulley as before. The principal member is rotated, using the handles, forcing the cam surface under the belt, so that the belt is twisted and stretched during this manipulation and the belt is slid from the pulley onto the removal device, thus removing it from pulley contact.
It is a principal object of this invention to provide a tool for installing and removing a power transmission belt without damaging the belt or other components.
It is a further object to operate the tool in a simple manner without other tools.
It is a further object to provide the tool with a secure mounting base to accomplish its purpose.
It is another object to provide the tool with separate installation and removal devices which may be locked in place.
These and other objects of the invention will become apparent from viewing the principal embodiment shown and described herein.

Tool for installation and removal of power transmission belts


The invention relates to a textile composite material used to stabilize, consolidate or reinforce soils and layers of earth, and which can also be used as a load-carrying drainage or filtering layer and comprises at least one nonwoven fabric (1). The disadvantage of nonwovens, used alone or in textile composites made of various plastic nonwovens, lies in their limited load-carrying capacity. To create a low cost textile composite material comprising at least one nonwoven fabric, having a high tear resistance in a main load direction and the ability to absorb high tensile forces without undue stretching, exclusively parallel, straight, load-carrying plastic filament yarns (2) are knitted, sewed or Raschel-knitted onto the nonwoven (1).

The invention relates to a textile composite material used to stabilize, consolidate or reinforce soils and layers of earth and as a load-carrying filtering layer, e.g. to cover a drainage layer, and comprising a nonwoven.
Nonwovens, especially plastic nonwovens, are used frequently in geotechnical engineeringxe2x80x94for example, in waste impoundment constructionxe2x80x94and in hydraulic engineering to separate two layers of soil having different particle size distributions. Different filtration characteristics can be obtained, depending on the thickness and strength of the nonwoven. Plastic nonwovens made from coarse fibers are suitable for use as drainage layers and are often combined with filtering nonwovens.
The disadvantage of nonwovens, used alone or in textile composites made of various plastic nonwovens, lies in their limited load-carrying capacity. Compared to textiles made of filament yarns (e.g. wovens or knits), nonwovens have much greater stretchability with lower tear resistance. Even textiles such as wovens and knits that possess high tear resistance, which are also used in geotechnical engineering, usually exhibit unfavorable load-carrying behavior, since the application of forces to such textiles initially causes elongation of the material due to the stretching of the yarns, which extend in curved paths as a result of the stitch formation or interweaving. Higher load-carrying capacity develops only after the material has undergone considerable stretching.
DE-A 37 28 255 discloses a ground anchoring strip that includes a loose nonwoven as a drainage material, fastened to the upper side of which, by clamping or sewing, is a textile strip comprising tensile-load-carrying warp strands. The textile strip must be manufactured on a weaving or knitting machine in a separate production step and then brought together with and joined to the nonwoven in a second production step.
The task of the invention is to create a low-cost textile composite material comprising at least one nonwoven fabric and which exhibits high tear resistance in a main load direction and can absorb high tensile forces without undue stretching.
This task is accomplished according to the invention in that exclusively parallel, load-carrying, straight, plastic filament yarns are woven, knitted, sewed or Raschel-knitted onto the nonwoven.
In the use of textile composites in geotechnical and hydraulic engineering, there is nearly always a fly established main load direction, e.g. the direction of inclination of a slope. By the simple expedient of applying exclusively parallel, straight, load-carrying strands made of plastic material, the textile composite material can be rendered highly tear-resistant in one direction, the main load direction. Since the strands lie straight against the nonwoven, when force is applied they are immediately stretched in opposition to their intrinsic elasticity, rather than being initially stretched with much lower resistance, as in the case of wovens and knits.
The plastic filament yarns extending in the warp direction can be applied to the nonwoven inexpensively, on sewing, knitting or Raschel-knitting machines, in a width that corresponds to the width of a web of nonwoven. Suitable plastic filament yarns can be selected according to the field of application and the required load-carrying capacity of the textile composite. One especially low-cost solution is to use split polypropylene yarn as the load-carrying strand and optionally also as the binding yarn for fastening the load carrier to the nonwoven, which can also be made of polypropylene.
The cross section of the strands can range from 2 to 100 mm2, depending on the material of the load-carrying strands and the distance therebetween. The load-carrying strands preferably have a cross section of 4 to 50 mm2 and are separated by a distance of 1 to 100 mm.
In an especially preferred embodiment of the invention, the load-carrying strands are Raschel-knitted onto the nonwoven in respective pairs, the distance between two pairs being 1 to 100 mm. This reduces the amount of binding yarn needed to secure the load-carrying strands. Of course, the connection between the nonwoven and the load-carrying strands is looser in this case than when the load-carrying strands are fastened individually, but such fixing of the load-carrying strands to the nonwoven is adequate. Once installed, both the load-carrying strands and the nonwoven are held in position by the pressure of the superjacent layers of earth.


The nerve growth factor (NGF) is used for the storage of corneas in culture, for the production and the storage in vitro of single cell populations of the corneal morphological and functional unit (i.e., epithelium, stroma/keratocytes and endothelium) and of the conjunctival epithelium, and for the production and the storage of corneal and conjunctival tissues, in particular for transplantation purposes.

The present invention relates to the use of nerve growth factor for the storage of corneas in culture, the in vitro production of corneal and conjunctival tissues and the treatment of corneal and conjunctival diseases. More particularly, the invention concerns the use of the neurotrophin named nerve growth factor (NGF)xe2x80x94known for its ability of influencing the development, the regeneration and the maintenance of the biological functions of neuronsxe2x80x94for the treatment of corneal and conjunctival tissues, both for properly maintaining their functionality in vitro and for the therapy of pathologies of the ocular surface.
As it is known, corneal graft represents the only therapeutic approach to dystrophic, inflammatory or degenerative corneal diseases in the event that the diseases have irreversibly compromised the transparency or the normal structure of the cornea. Once isolated from cadaver, the corneas are xe2x80x9cstoredxe2x80x9d up to the time when they are transplanted, by means of storage methods employing liquids derived from cell culture mediums. According to one of the most common methods, called xe2x80x9cshort/intermediate term storagexe2x80x9d, the cornea is kept at 4xc2x0 C. in culture mediums such as McCarey-Kaufman (MK) medium, or in different commercial liquids (among which Optisol-GS ), for a maximum period of 7 days. A longer term storage is possible with an equally common method, referred to as xe2x80x9corgan culturexe2x80x9d. This method is based on techniques similar to cell culture, and allows to store the explanted corneas, at temperatures comprised between 30 and 36xc2x0 C., for more than one month.
None of the above methods affords an improvement of the biological features of the corneal tissues with the storage, the best result achievable being that of maintaining unchanged the quality of the tissues during the storage. This co-operates in making even more critical the already difficult situation in the field of corneal graft. Actually, more than one half of the corneas are discarded upon explantation, since the microscope examination shows them to be unsuitable for transplant.
Another major problem is represented by the need of having available single corneal cell populations, such as endothelial cells, epithelial cells and keratocytes, so as to be able to use them for transplantation. In particular situations involving the destruction of the ocular surface due to physical or chemical burns, or resulting from synechiating autoimmune diseases (such as cicatricial pemphigoid, Stevens-Johnson syndrome, etc.) or from post-infectious pathologies, it is of a critical importance to have available corneal epithelial cells (including stem cells) to be transplanted in place of the damaged ocular surface, and/or to have available conjunctival epithelial tissue for use in replacing the synechiated and retracted surface.
Considering the pathological situations that may affect the morphological and functional unit consisting of cornea (i.e., epithelium, stroma/keratocytes and endothelium) and conjunctiva, it is noted that there is a wide variety of disorders affecting this region which are, to date, of a difficult therapeutic approach, or are totally orphan of a valid treatment. Such pathologies or situations which may interfere with the normal surface integrity include all the impairments of the tear film functions, congenital or acquired corneal and/or conjunctival affections such as: neurotrophic and neuroparalytic keratitis and/or conjunctivitis; post-traumatic, post-infectious, post-surgical keratitis and/or conjunctivitis; keratitis and/or conjunctivitis due to laser treatment, to chemical, physical or metal burns; autoimmune, dystrophic, degenerative, post-inflammatory keratitis. These diseases appear with alterations of the corneal epithelium (spontaneously in the primary neuroparalytic forms or on a physical, infectious, immune or toxic basis in the secondary forms) which may end in an ulcer, leading in most cases to corneal perforation, either spontaneously or following microtraumas or superinfections. The clinical picture of this disease is characterized by a slow and difficult recovery, by superinfections and by the frequent failure of any therapy. The final outcome is often the opacification of the cornea, or the spontaneous perforation thereof.
The above diseases are generally treated by having recourse to bandage and to the use of lubricating substances and antibiotics, with a view to prevent the complications. The conjunctival covering is necessary when the perforation is imminent or has already occurred, and has the only purpose of preserving the anatomic integrity of the eyeball, while the visual function is sacrificed. The corneal graft, both by lamellar and by penetrating keratoplasty, is absolutely contra-indicated in view of the frequent occurrence of relapses even on the transplanted graft, and in view of the risk of superinfections. On the basis of in vitro studies the topical medical treatment with preparations containing fibronectin, plasmin, collagenase inhibitors, EGF (i.e., epidermal growth factor), autoserum has also been proposed. None of these drugs turned out to be resolutive, or able to block or to reduce the corneal injury, or to modify the final outcome of the pathology.
In particular, in the treatment of corneal burns quite good results have been obtained with the transplantation of marginal conjunctiva taken from the contra-lateral eye. When the affection is bilateral, recourse may be had to the donation of conjunctiva by close relatives or, when this is not possible, to the excision from cadaver. However, this method is not resolutive in the totality of the cases. In the case of autograft relapses of the disease may occur after years, while in the case of homograft rejection is frequent, and an immunosuppressive therapy is absolutely necessary, with the well-known consequences due to the side-effects.
Another kind of corneal-conjunctival diseases the treatment of which often gives unsatisfactory results are the herpetic infections. After the resolution of a first pathologic occurrence, herpetic infections often give rise to relapses, the prevention and the treatment of which are often unsuccessful.
Also the diseases affecting the corneal endothelium, such as, e.g., primary and secondary decompensation and endothelitis, characterized by a loss in the number and/or in the function of endothelial cells, represent a group of affections which presently lack any effective treatment.
Therefore, it is a primary object of the present invention to provide a solution to the problems referred to abovexe2x80x94which problems are all related to the physiopathology of the corneal and conjunctival morphological and functional unitxe2x80x94by means of the use of a therapeutic agent allowing to maintain and restore the proper biological activity of the tissues.
The molecule known as nerve growth factor (NGF) is the first component of a complex family of neurotrophins, and is well-known for its trophic, tropic and differentiating action on cholinergic neurons of the central nervous system and on the peripheral sympathetic system. NGF is produced in several tissues in mammals, including man, and is released in the blood stream at higher levels during the growth and the differentiation of the nervous system. Biological, biochemical and molecular studies carried out in vitro on cell systems have evidenced a very high homology between murine NGF and human NGF. In man as in other animal species the NGF is normally present both in the cerebrospinal fluid and in the blood stream at levels of about 10-50 pg/ml. These concentrations increase in some inflammatory pathologies (autoimmune diseases, allergic diseases, etc.) and decrease in other pathologies (diabetes).
The NGF was discovered in 1951 by Prof. Rita Levi-Montalcini, of the Zoology Institute of the Washington University of St. Louis (see Levi-Montalcini R., Harvey Lect., 60:217, 1966) and represented a major advance in the study of the growth and differentiation mechanisms of the nerve cell, as it is capable of influencing the development and the maintenance of the biological functions of neurons and their regeneration. For the discovery of this molecule, for having characterized its biological role both in the peripheral nervous system and in the central nervous system, Prof. R. Levi-Montalcini was awarded in 1986 the Nobel prize for Medicine and Physiology.
Several experimental studies, both in vitro and in vivo, have shown the physiopathological importance of the NGF in preventing neuronal injury of a surgical, chemical, mechanical and ischemic nature, thereby making it the ideal candidate for use in the therapy of several diseases of the central and peripheral nervous system (Hefti F., J. Neurobiol., 25:1418, 1994; J. Fricker, Lancet, 349:480, 1997). Indeed, clinical trials on patients suffering from Parkinson""s disease and from Alzheimer""s disease have already started since some years. These trials are carried out by intracerebral administration of murine NGF (see, e.g., Olson L. et al., J. Neural Trans.: Parkinson""s Disease and Dementia Section, 4: 79, 1992). The results of the studies confirmed the observations made on animal models and evidenced the absence of any possible side-effects upon administration of murine NGF. This feature has more recently been confirmed as regards human recombinant NGF (Petty B. G. et al., Annals of Neurology, 36:244-246, 1994).
Ever since its discovery, the studies on the NGF, i.e. on the characterization of its biological, biochemical, molecular, preclinical and clinical effects have been carried out almost exclusively with NGF isolated from the submaxillary glands of adult rodents; thus, the widest amount of data acquired to date concerns murine NGF. The biochemical properties of the latter have been described, in particular, in a work dating back to 1968 (Levi-Montalcini R. and Angeletti P. U., Physiological Reviews, 48:534, 1968).
The NGF contained in the salivary glands of mice is a 140 kdalton molecular complex, with sedimentation coefficient 7S, consisting of three sub-units, xcex1, xcex2 e xcex3, the second one of which represents the true active form. This sub-unit, called xcex2NGF, with sedimentation coefficient 2.5S, is normally extracted and purified according to three methods which are not very different from each other (Bocchini V., Angeletti P. U., Biochemistry, 64: 787-793, 1969; Varon S. et al., Methods in Neurochemistry, 203-229, 1972; Mobley W. C. et al., Molecular Brain Research, 387: 53-62, 1986).
The xcex2NGF obtained with such methods is in turn a dimer of about 13,000 dalton, consisting of two identical chains of 118 amino acids. Each single chain is stabilized by three disulfide bridges, while non-covalent bonds provide to the formation of the dimer structure. This molecule, being very stable, may dissolve in almost every solvent, both aqueous and oily, while keeping unaltered its biochemical features and its biological activity. Further information on the structure and the physical and biological properties of the molecule can be found in Greene, L. A. and Shooter, E. M., Ann. Rev. Neurosci. 3:353,1980.
Recently, the structure of the xcex2NGF has been further elucidated by means of a crystallographic analysis. The latter detected the presence of three antiparallel couples of strands, with secondary structure of the xcex2 kind, which co-operate in forming a planar surface along which the two chains associate to form the active dimer. On chains of the xcex2NGF there has been evidenced the presence of four loop regions containing many variable amino acids. To these variable amino acids is connected, very likely, the specificity of the recognition by the receptor.
The biological effect of the NGF is mediated by two receptors present on the surface of the respective target cells. There are several antibodies which selectively inhibit the biological action of NGF. The existence of the antibodies has allowed and allows to accurately characterize and modulate the NGF activity, both in cell systems and in vivo.
In more recent times it has become possible to synthesize human NGF with genetic engineering techniques (Iwane, M. et al., Biochem. Biophys. Res. Commun., 171:116, 1990), and small amounts of human NGF have been placed on the market. However, direct experimentation has shown that the biological activity of human NGF is quite low in comparison with the biological activity of murine NGF. In addition, it is to be considered that almost all of the data presently available on the effects on man, both in vitro and in vivo, have been obtained by using murine NGF, and that no adverse effects have been detected which may be connected to the murine origin of the product.
Studies carried out starting from the nineties on animal models suggested a possible involvement of the NGF in ocular pathologies. However, such studies almost exclusively concern the use of NGF in retinal affections, i.e. on the nervous tissue, while nothing is present in the literature about an effect of this neurotrophin on the ocular surface (i.e., cornea and conjunctiva), nor are there any scientific works proposing the use of the NGF for the treatment of diseases affecting the cornea and/or the conjunctiva. In particular, some studies have been carried out on animals in order to ascertain the effect of the topical administration of NGF in the treatment of retinal pathologies, for instance in the treatment of acute retinal ischemy (Siliprandi R. et al., Inv. Ophthalmol. Vis. Sci., 34:3232, 1993), in the transection of the optical nerve (Carmignoto G. et al., J. Neurosci., 9:1263, 1989) and in the treatment of retinitis pigmentosa (Lambiase A. e Aloe L., Graefe""s Arch. Clin. Exp. Ophthalmol., 234: S96-S100, 1996). The results demonstrated that the topical administration of NGF can prevent, or at least delay, the death of the retinal ganglion cells and of the photoreceptors during the above pathologies. None of these studies evidenced side-effects on animals.
On the other hand, with reference to the diseases of the corneal tissues which are the object of interest of the present invention, several Authors have considered for such indications the possible employment of the epidermal growth factor (EGF), starting from the assumption that alterations of the corneal epithelium represent the pathogenic key to the development of other corneal affections, such as ulcers and keratites.
The EGF is a 53 amino acid polypeptide discovered and characterized in the early sixties (Cohen S., J. Biol. Chem., 237:1555-1562; 1962), having a molecular weight of about 6000 dalton. This molecule is produced by the salivary gland of adult mice, but it is present in small amounts in many human tissues. The EGF exerts a well-characterized trophic, proliferative and differentiative action on the epithelial cells obtained from various animal and human tissues, and its in vitro effectiveness on corneal epithelial cell cultures, as well as its capacity of inducing proliferation and differentiation of these cells are described in some experimental works.
However, the clinical studies on corneal diseases which have been carried out on the basis of the above experimental data gave contradictory results, and showed, in general, a substantial ineffectiveness of the EGF in this kind of human diseases (Kandrakis A. S. et al., Am. J. Ophthalmol., 98:411, 1984). The ineffectiveness may be ascribed, probably, to a different expression of the EGF receptor in vitro and in vivo or, more likely, to the fact that epithelial alterations in corneal diseases would only represent an epiphenomenon of the corneal disease itself.
EP-A-0 312 208 (Ethicon) discloses gel formulations for use in the treatment of epithelial lesions and epithelial pathologies in general, including lesions and pathologies of the ocular surface. The formulations contain an active ingredient which may be indiscriminately chosen among the various molecules whose name contains the expression xe2x80x9cgrowth factorxe2x80x9d Although the description is exclusively concerned with the EGF as the preferred active ingredient, and although activity data (in vitro) and formulation examples are given only for the EGF, other growth factors are mentioned as well, such as FGF (fibroblast growth factor), PDGF (platelet-derived growth factor), TGF-xcex1 (transforming growth factor) or the NGF itself. The above growth factors are apparently presented as a family of molecules having the same features and the same biological activity as the EGF. As a matter of fact, at the current state of the knowledge, the expert is aware that the above growth factors have different specific targets and that they often have conflicting effects, and does not consider the growth factors as biologically equivalent to each other. Besides, as far as the ophthalmic field is specifically concerned, the above document describes the growth factors as active exclusively on the corneal epithelium, thus reducing the proposed indication to an indication as re-epithelizing factors, useful, in practice, only in traumatic affections.
The studies that led to the present invention started from the concept of cornea as a morphological and functional unit, wherein the single layers (i.e. epithelium, stroma and endothelium) all carry out a function of an equal importance in the preservation of the tissues integrity and in the recovery mechanisms. In this perspective, a key role is played by the trophic support offered by the corneal sensory innervation, whose damage brings about a damage to the whole morphological and functional unit.
In view of the fact that no evidence existed in the prior art of an effect of the NGF (i.e., one of the many mediators released by the sensory endings in other regions of the body) on the ocular surface, the question has been initially posed whether such neurotrophin might play a trophic-reparatory action on the corneal tissue of neuroectodermal embryonal derivation, since several targets of the neurotrophin show a similar embryogenetic derivation. Thus, cornea and conjunctiva have been analyzed for the presence of the NGF and of the NGF high affinity receptor (TrkA, tyrosine kinase A), using a monoclonal antibody (TrkA-antibody; Santa Cruz, USA) with immunohisto-chemistry techniques (Bhattacharyya A. et al., J. Neurosci. 17:7007, 1997). In fact, the presence of the specific receptor is a key requirement for the activity of the molecule under examination.
It has thus been found that all of the corneal cells (i.e., epithelial cells, endothelial cells and keratocytes) express TrkA and that, at the same time, the corneal somatosensory innervation is able to release NGF. This discovery allows to hypothesize, on one hand, that the NGF, probably released by the nerve endings, would play a physiopathologic role in all corneal reparative mechanisms (both at the surface and at a deeper level) and, on the other hand, that several superficial corneal diseases accompanied by primary damage to the innervation (such as neurotrophic or dystrophic keratitis and recurrences of herpetic infections) or with secondary damage to the innervation (such as chemical or physical burns and post-infectious, autoimmune, post-surgical lesions, or lesions resulting from laser treatment) would admit as a fundamental etiologic step the lack of NGF release.
The same finding also allows to hypothesize that the NGF would be essential to the maintenance of the whole corneal tissue in culture, i.e. in all such conditions wherein the cornea as a whole, intended as a morphological and functional unit comprising epithelium, stroma and endothelium, or some cells thereof, are deprived of the trophic support provided by the release of the NGF by the corneal nerve endings.
In addition, since the effects that have been observed after administration of exogenous NGF occur at concentrations close to the physiological level it can be hypothesized that a possible physiopathogenic mechanism in the corneal affections considered herein consists in a reduction of the local levels of the NGF below the threshold capable of assuring the corneal and/or conjunctival integrity.
Accordingly, the present invention specifically provides, according to a first aspect thereof, the use of the nerve growth factor for the storage of corneas in culture and for the storage and the production in vitro of corneal and conjunctival tissues, and of single corneal or conjunctival cell populations.
Preferably, the NGF is added to a culture medium of the kind suitable for the storage of corneas, or for the in vitro culture of corneal or conjunctival cells or tissues, in amounts comprised between 100 pg/ml and 200 ng/ml, optionally together with other nutrients and other biologically active agents. The NGF to be used to that aim can be of a murine or human origin, including recombinant NGF, and it may be used in lyophilized form, dissolved in solution, in a culture medium or in any other available solvent, so as to obtain a final concentration comprised in the range specified above.
Suitable methods of extracting and purifying the NGF are reported in the literature mentioned above. For the purpose of experimenting the present invention, the Bocchini and Angeletti technique (cited above) has been adopted, the latter being synthetically set forth below. The submaxillary glands of adult male mice are explanted under sterile conditions and the tissues are homogenized, centrifuged and dialyzed; then the suspension is passed through subsequent cellulose columns, thereby separating the NGF by adsorption. The NGF is then eluted from the column by means of a buffer containing 0.4 M sodium chloride. The samples so obtained are analyzed by spectrophotometer at a wavelength of 280 nm to identify the NGF-containing fractions. The latter are dialyzed, and the NGF thus obtained is lyophilized under sterile conditions and kept in refrigerator at xe2x88x9220xc2x0 C.
In an evaluation of the effects of an addition of NGF to various culture mediums for explanted corneas (both at 4xc2x0 C. and at 30-36xc2x0 C.), a general improvement of the biological features of the corneal tissue has been obtained with amounts of NGF comprised between 100 pg/ml and 200 ng/ml. The optimal response has been obtained with a concentration of about 100 ng/ml. Specifically, after 7 days of culture the improvements obtained were an increase of the endothelial cells density (increase from 10 to 25%), a reduction of the endothelial cells mortality (absence of trypan blue positive endothelial cells), a better endothelial morphology (i.e., quantitatively, a 3/3 trophism vs. a 2/3 trophism in the controls without addition of NGF), a higher viability of the keratocytes and a remarkably better appearance of the epithelium. In addition, some corneas that before being placed in culture were considered not suitable for transplantation turned out to be suitable after being cultured for 7 days in presence of NGF.
A similar experimental evaluation of the effects of the NGF as additive in the culture medium of corneal cells (i.e., epithelial cells, endothelial cells and keratocytes) showed that the addition of murine NGF in amounts comprised between 100 pg/ml and 200 ng/ml (with an optimal response at the concentration of about 100 ng/ml) induces the proliferation and differentiation of the various cell populations, and, moreover, it assists the rooting of the cell populations on a number of supporting tissues (such as lamellae of corneal stroma, amniotic membrane, etc.). Further, such addition favors the interaction between the different cell types in cell co-cultures. Thus, the invention may be also employed for culturing mixed corneal cell lines in order to obtain an artificial cornea useful for transplantation.
Also the conjunctival epithelial cell cultures have shown a proliferation and differentiation increase, as well as an increase in the number of goblet cells, when cultured in presence of murine NGF at the same concentrations specified above. The graft of epithelial conjunctival tissue thus obtained is extremely advantageous for replacing the conjunctiva of patients suffering from kerato-conjunctivitis sicca (dry eye syndrome), both primary and secondary to other pathologies.
According to another aspect of the invention, there is provided, therefore, a culture medium for the storage of corneas or for the storage and the production in vitro of corneal and/or conjunctival tissues, or of single corneal or conjunctival cell populations, characterized in that it contains an effective amount of NGF, preferably comprised between 100 pg/ml and 200 ng/ml, most preferably about 100 ng/ml.
As set forth before, according to a further aspect of the invention there is provided the use of the nerve growth factor in the manufacture of a medicament for the therapy and/or the prophylaxis of corneal and/or conjunctival diseases.
Specifically, the invention is useful for the production of medicinal products suitable for the treatment and/or the prophylaxis of congenital and/or acquired corneal and/or conjunctival diseases chosen from the group consisting of: neurotrophic and neuroparalytic keratitis and/or conjunctivitis; herpetic keratitis and/or conjunctivitis; post-traumatic, post-infectious, post-surgical keratitis and/or conjunctivitis; keratitis and/or conjunctivitis due to impairment of the tear film functions, to laser treatment, to chemical, physical or metal bums; autoimmune, dystrophic, degenerative and post-inflammatory keratitis.
Preferably, a medicinal product according to the invention suitable for topical administration contains, alone or in combination with one or more other active ingredients, from 10 to 500 xcexcg of NGF per ml, an optimal concentration being about 250 xcexcg of NGF per ml. Such product may be in the form of ophthalmic solution for eye-drops, or in the form of a gel, an ointment, a cream or a powder, or it can be added to a local bandage or to a medicinal contact lens.
According to another embodiment of the invention, the pharmaceutical product for the manufacture of which the NGF is proposed is a medicament indicated for the therapy and/or the prophylaxis of primary and secondary endothelial ophthalmic pathologies. For this use, the preferred formulations contain (also in this case optionally in combination with other active ingredients) from 1 to 250 xcexcg of NGF per ml, and the administration is carried out by introduction in the anterior chamber of the eye.
In vivo studies on animals concerning the treatment of disorders of the corneal endothelium have been carried out by administration in the anterior chamber of the eye of aqueous solutions containing NGF at concentrations comprised between 1 and 250 xcexcg/ml. In particular, in rabbits wherein an endothelial damage had been introduced by means of a cryoprobe a complete restoration of the endothelial density has been obtained after 15 days of treatment with NGF. The administration of NGF in endothelial pathologies, both of a dystrophic nature and acquired, both with loss of the number of endothelial cells and with loss of the functionality thereof, has been shown to restore a proper endothelial function.
In a series of studies on man for ascertaining the efficiency of the treatment with NGF in the topical treatment of corneal and/or conjunctival affections, a number of pathologies have been selected on the basis of a primary or secondary involvement of the somato-sensorial corneal nerve plexus. Murine NGF (2.5S), obtained with the purification method summarized above, has been employed in such studies. The NGF has been topically administered at a concentration of about 250 mg/ml, diluted in balanced salt solution.
The table shown further on summarizes the results obtained from a study on 5 patients affected by torpid corneal ulcer due to neurodistrophic keratitis (2 eyes), or after keratoplasty (2 eyes) or due to bum by alkali (2 eyes). The therapeutic schedule consisted in the instillation of one-two drops of the preparation of the invention with a daily frequency divided as follows: every 2 hours for the first 2 days, 6 times a day up to the 2nd day after the complete re-epithelization of the cornea and twice a day for the following 15 days.
The topical treatment with the NGF was started after 15 days of treatment with autoserum, in the absence of signs of improvement of the clinical picture. All of the patients treated showed clear signs of recovery within 2 weeks from the start of the treatment with NGF, and none of them evidenced any occurrence of local or systemic side-effects during the treatment or in the following period. Once suspended, the therapy should be immediately restored in the event that the first signs or symptoms of any relapse of the epithelial pathology appear.

Use of nerve growth factor for the storage, culture or treatment of cornea

Abstract: The NGF is also proposed for use in the therapy and/or the prophylaxis of diseases of the corneal surface, wherein a lack of integrity of the corneal and conjunctival morphological and functional unit occurs, in particular for pathologies having a dystrophic or neurodystrophic basis, both congenital and acquired.


It is believed that rheumatoid arthritis and related collagen and auto-immune diseases are an infection and that various species of free-living (limax) amoebae are the aetiological agent of these diseases. It has been discovered that pyrimidines with anti-protozoal activity, are effective for the treatment of rheumatoid arthritis and other collagen and auto-immune (rheumatoid) diseases.

Men and other animals are continually exposed to infection and re-infection by various species and strains of free-living limax amoebae which can be detected in the faeces, nasopharynx and bronchi. In all parts of the world they form part of the environment. Experimentally in animals they induce changes like those of collagen and auto-immune diseases and are characterized by vasculitis, myosotis hepatitis, pyelitis and splenomegaly. They can often be seen in the tissues of animals. Such animals shown lymphadenopathy with an appearance like that of human Hodgkin's disease or a state like that of advance malignant disease. These organisms may also be recovered from all the tissues of cases of collagen and auto-immune diseases and from human and many animal tumors and may also occur in the tissues of apparently healthy individuals. They cannot be identified in ordinary histological sections, but can be demonstrated by immunofluoresence methods.
The definite cause of rheumatoid arthritis is presently unknown. Rheumatoid arthritis is a crippling disease involving any tissue including inflammation of several joints of the body, with swelling, pain and stiffness. Rheumatoid arthritis is a disorder that afflicts about fifteen million people in the United States alone. Successful early treatment may avert the destructive, deforming phase of the disease. Therapy has been directed largely at non-specific suppression of inflammatory and immunologic processes. Aspirin is the cornerstone of therapy for rheumatoid arthritis and can reduce synovial inflammation, improve function and reduce pain in a majority of patients in view of its analgesic action. Widespread interest in rheumatoid arthritis arose when Hench (1949) introduced the use of cortisone in treatment. Chemical compounds which have been commonly used in treating rheumatoid arthritis are corticosteroids, gold salts, antimalarial drugs, immunosuppressive agents and a whole range of so-called non-steroidal drugs, e.g. indomethacin, phenylacetic acid (Ibuprofen), propionic acid (Naproxen) and D-Penicillamine. Most of these drugs bring temporary relief to the arthritic patient but present the danger of side effects and the physician has to balance the potential benefit against the risks. However, arthritis reoccurs following withdrawal of such chemical treatment. For many years rheumatoid arthritis was considered to be an infection (Hollander et al., 1960; Robinson, 1967), but with the advent of the concept of auto-immunity this idea lost favor. Such a view has recently been revived (Lancet, 1970, 2, 303) and is supported by many observations. It is highly likely that the limax amoebae, found in all the collagen and auto-immune diseases, may well be the aetiological agent of these conditions and that antiprotozoal drugs may help by their action on these organisms. The term rheumatoid arthritis and related diseases is to be understood to include diseases such as lupus erythematosis scleroderma, psoriasis, dermatomyositis, polymyositis. periartheritis nodosa. chronic ulcerative colitis, Still's disease.
The use of a bis-phenyl (2-halophenyl)-1-imidazolylmethane or clotrimazole for treatment of Rheumatoid Arthritis is disclosed in my U.S. patent application Ser. No. 700,914 filed June 29, 1976 now U.S. Pat. No. 4,073,922, issued Feb. 14, 1978, and the use of tinidazole is disclosed in my U.S. Pat. No 4,119,723. It has also been suggested to use a nitroimidazole in the treatment of rheumatoid arthritis in the Journal of Tropical Medicine and Hygiene (Vol. 75) pags. 64 to 66 March 1972. It is believed that the nitro group in the imidazole ring is related to metronidiazole which is not effective in the treatment of rheumatoid arthritis in small doses. Various other anti-protozoal drugs were tried on the cases of rheumatoid disease or of various localized manifastations of this. The substances investigated were 4-aminoquinolines (chloroquine), hydroxychloroquine (plaquenil), amodiaquine (camoquin); copper sulphate; bile salts (dehydrocholine), which are effective in killing the trophozooites of many amoebae in the concentration found in the small intestine; and clotrimazole (canesten). All of these were actually shown experimentally to kill limax amoebae. In addition, other antiprotozoal drugs were also investigated. They included suramin, pentamidine, dehydroemetine (DHE or mebadin), metronidazole (flagyl), nimorazole (naxogin (Erba)), phanquone (entobex) and diloxanide (furamide).
It has been found that certain pyrimidine compounds which have antiprotozoal activity are effective when administered internally for treating rheumatoid arthritis and related collagen and auto-immune (rheumatoid) diseases. Of this group of compounds, allopurinol (4-hydroxypyrazolo [3,4-d] pyrimidine) has proven most effective. These compounds have the following chemical structural formula: ##STR1## wherein R' is amino, hydroxy or mercapto and R.sup.2 is hydrogen, mercapto or hydroxy. The salts of such pyrimidines are the pharmaceutically acceptable non-toxic acid addition salts. Examples of suitable acids are the hydrohalic acids (hydrochloric being particularly preferred), phosphoric acid, mono- and bi-functional carboxylic acids, such as acetic acid, propionic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, citric acid, salicylic acid, sorbic acid, lactic acid and 1.5-napththalene-disulphonic acid. The hydrohalides, especially the hydrochlorides, lactates and salicylates are of particular value.
The method of determining the anti-protozoal activity of drugs on limax amoebae was described by Fulton, C. Methods in Cell Biology (edited by C. M. Prescott), p. 341, New York, 1970 and followed by Jamieson and Anderson in Lancet, 1974, 1, 261. All experiments were performed using 5-day-old 5 ml. cultures of amoebae in the axenic medium "A" of Fulton. A standard inoculum of 100 c.mm. of differing concentrations of amoebae was addaed to each 1 ml. tube containing the dilutions of the compound to be tested (dissolved initially in dimethyl sulfoxide) or other drugs in the axenic medium. The tubes were incubated for 5 days and 37 C. and the final concentration per c.mm. was compared with the initial count to determine percentage kill.
The diagnosis of active rheumatoid arthritis in 6 cases, was consistent with the criteria of the American Rheumatism Association. The patients were not hospitalized or confined to bed. They continued to take the drugs they were being treated with when first seen. Serial investigations were carried out before and repeatedly during and after treatment. Allopurinol was administered orally in a dosage of 300 mgs (three doses per day) for ten days. Suitable doses range from about 4 to 20 g per kilogram of body weight. With this dosage of the drug beginning 24-36 hours after taking it there almost invariably occurs an exacerbation of the active inflammatory changes in the affected joints with increased heat, pain and swelling and other parts of the body not previously affected may also be involved with generalized malaise and often sweating. This may last for 2-3 days and then disappear with general improvement in the patients' symptoms. With successive doses this reaction becomes less and finally disappears and as the course of treatment progresses the signs of active rheumatoid disease also disappears. This response constitutes an Herxheimer reaction and its occurrence with allopurinol and antiprotozoal drug, indicates with certainty the presence in the affected tissues of an organism which is acted on by allopurinol. Steroids and other treatments may then be tapered off. Allopurinol was administered to patients of ages from 22 to 66 years. Symptoms had been present for 1.5 to 15 years. Patients have been followed for 6-9 months without evidence of recurrence of activity of the disease and with return of the sedimentation rate to normal. The drug thus eventually completely reversed all the manifestations of activity in rheumatoid disease when other drugs had failed.
The therapeutically effective compound can be used either as such or in combination with pharmaceutically acceptable carriers. Suitable forms of administration in combination with various inert carriers are tablets, capsules, powders, aqueous suspensions, syrups and the like. In the aforesaid case, the therapeutically active compound should be present in the total mixture at a concentration of about 0.5 to 90 percent by weight, i.e., in quantities which suffice to attain the range of dosage mentioned above. Tablets may also contain fillers such as starch, avicel, lactose, calcium carbonate or dicalcium phosphate together with various additives such as dyes and binders such as polyvinylpyrrolidine, methylcellulose, gelatin and the like. It is further required to add lubricants such as magnesium stearate, sodium lauryl-sulphate and talc for producing tablets. Tablets may be filmcoated.

Treatment of rheumatoid arthritis and related diseases


Device for drying washed and rinsed crates or cases, comprising a frame and receiving or accommodation spaces carried by the frame for the crates or cases, in which the accommodation spaces are attached to a rotating shaft and are situated on either side of it in a symmetrical manner, and furthermore comprising means for rotating the rotating shaft and thus the accommodation spaces in order to cast off the water present on the crates or cases from them through centrifugal forces.

The invention relates to a device for drying washed and rinsed crates or cases.
Crates and cases are used by the wholesaler, auction hall, factory and the like for containing and transporting all sorts of products. After the products have been sold at the retailer""s the crates are returned. The crates are then washed in order to be used again.
In the course of time the wish arose to have disposal of not only cleansed, but also dry crates. To that end various dryers have been thought up, such as compressed-air-operated blowers. A drawback of this however is that for a quick treatment of the crates to be dried a lot of so-called flat-airblasting nozzles are necessary and therefore a lot of (expensive) compressed air.
Alternatively high-pressure fans are also used, which however requires a high power, otherwise the drying capacity is to limited.
Shake devices are also used, but still quite a lot of attached water is left behind on the crates.
Crates are also dried with the help of hot air, in connection with fans. The crates are often made of synthetic material, as a result of which they do not absorb heat very well and the drying process takes quite a long time.
Another alternative is drying crates with the help of infrared radiation, but here again there is the drawback that the crates are made of synthetic material and therefore do not conduct heat very well.
Finally the drying of crates under vacuum is mentioned. The advantage of this is that a lower temperature can be worked with, but a drawback is that special xe2x80x94and therefore expensivexe2x80x94measures have to be taken in order to realise a vacuum surrounding.
It is an object of the invention to improve on this. To that end the invention provides a device for drying washed and rinsed crates or cases, comprising a frame and receiving or accommodation spaces carried by the frame for the crates or cases, in which the accommodation spaces are attached to a rotating shaft and are situated on either side of it in a symmetrical manner, and furthermore comprising means for rotating the rotating shaft and thus the accommodation spaces in order to cast off the water present on the crates or cases from them through centrifugal forces.
By using centrifugal forces the crates can be dried quickly with simple equipment. It is noted here that it is known per se to rotate crates quickly in order to dry them, but a vertical stack of crates is then rotated about the stack axis, during which imbalance may occur and the centrifugal forces often turn out to be insufficient.
Preferably the rotating shaft is horizontally positioned. This facilitates connection to supply and discharge devices for the crates to and out of the drying device, respectively, preferably parallel to its rotating shaft.
Preferably the accommodation spaces have boundaries that are adjustable in distance one to the other, so that a positive placement in the accommodation spaces can be realised for either various heights or widths between sets of crates.
The crates are kept in their places in a simple manner when the boundaries of the accommodation spaces comprise angle sections destined for engaging about the longitudinal edges of the crates.
Preferably the device is furthermore provided with a screen stationary with the frame for radially outward stopping of the water cast off from the crates, and with a collection tray for water intercepted by the screen.
From another aspect the invention provides an assembly of a device according to the invention and a supply device for crates to be dried and/or discharge device for dried crates, in which either the supply device or discharge device is in line with or can be brought in line with at least one accommodation space.


At least one-sidedly self-adhesively treated backing material which is coated partially with a self-adhesive composition and which under a tensile load of 10 N/cm has an extension of greater than 10% so that the backing material following application can be detached from the substrate by pulling in the direction of the bond plane.

The invention relates to a backing material which has been self-adhesively treated on at least one side and which is partially coated.
Adhesively coated backing systems which unstick when the backing is pulled are known. They are generally based on elastic systems, which in many cases constitute laminates.
DE-A 27 28 346 describes such a laminate, consisting of an extensible film and an adhesive composition based on A-B-A block copolymers. The laminate, adhering in its entirety, is easily detached from the substrate by stretching.
The adhesive composition is always applied over the entire area. However, such whole-area application is associated with a large number of disadvantages which greatly restrict use in the medical sector, in particular. Whole-area application entails the need for large quantities of adhesive composition, which makes the production process and hence the end product as well more expensive. In addition, it is important that the backing material coated with the adhesive composition continues, following its application to the skin, to be permeable to air and water vapour, in order, for example, that perspiration can be transported away from the skin. This property is possessed only to a very limited extent, if at all, by a wholly coated backing.
DE-A 195 31 696 describes an adhesive-film laminate which is produced from an extensible backing and an acrylate adhesive composition.
WO 95/06691 discloses a redetachable adhesive tape having a foam as its backing material.
WO 92/11333 describes a system which can be removed nondestructively and possesses high tear strength. Likewise, however, partial coating is not described.
It is also known to apply self-adhesive compositions to backing materials for sheetlike structures which can be redetached without residue, and/or for medical applications, not only over the entire area but also in the form of a pattern of dots for example by means of screen printing (DE-C 42 37 252), in which case the dots of adhesive can also differ in their size and/or distribution (EP-B 353 972), or by intaglio printing, in lines which interconnect in the longitudinal and transverse directions (DE-C 43 08 649). The documents listed, however, do not describe a detachment effect (stripping effect) induced by extension of the respective backing in the orientation of the backing.
All of the systems described above have a serious disadvantage in that they have been coated over the entire area. As a result, redetachment requires a comparatively high force, thereby reaching the limit of the strength of the backing materials.
A further disadvantage of these backing materials is that in the case of whole-area coating the systems used may use their elasticity if the adhesive systems employed are of lower elasticity.
For processing, the abovementioned adhesive compositions may be present in a carrier matrix. The term carrier matrix is understood to refer to common organic or inorganic solvents or dispersion media.
Systems without a carrier matrix are referred to as 100% systems and are likewise not unknown. They are processed in the elastic or thermoplastic state. A common mode of processing is that of the melt.
Hotmelt adhesive compositions of this kind have also been described in the prior art. They are based on natural or synthetic rubbers and/or on other synthetic polymers.
Because of their high level of hardness, sticking to the skin is a problem for such 100% systems.
An advantage of the 100% systems is that they avoid an operation of removal of the carrier matrix, i.e. the auxiliary media, thereby raising the productivity of processing and at the same time reducing the expenditure on machinery and the energy costs. In addition, this reduces the occurrence of residues of the carrier matrix, which, in turn, is to the benefit of a reduction in the allergenic potential in the case of use specifically for bonding to the skin.
The object of the invention was to avoid the disadvantages known from the prior art and to provide an at least one-sidedly self-adhesive backing material which following application to the skin can be redetached by extension in a simple manner and, especially when used as a medical product, painlessly.
This object is achieved by an at least one-sidedly self-adhesively treated backing material which is partially coated with an adhesive composition and has an extension of more than 10% under a tensile load of 10 N/cm, so that following application the backing material can be detached from the substrate by pulling in the direction of the bond plane.
Under a tensile load of 10 N/cm the backing material preferably has an extension of more than 15% up to 3000%, with particular preference from 20% to 1000%.
It has been found advantageous that with the use of backing materials permeable to water vapour or air and at high application rates of more than 15 g of composition per m2, the adhesively, treated products had an extremely high permeability.
Suitable backing materials are extensible sheetlike structures composed of synthetic and natural raw materials. Preference is given to backing materials which, following the application of the self-adhesive composition, can be used in such a way that they fulfill the characteristics of a functional bandage. Examples are textiles such as wovens, knits, lays, nonwovens, laminates, nets, films, foams and papers having an extensibility of at least 10% under a load of 10 N/cm.
Combinations of these materials are also suitable.
In addition, these materials can be pretreated or aftertreated. Common pretreatments are corona and hydrophobicization; customary aftertreatments are calendering, thermal conditioning, laminating, punching and lining, UV/IR irradiation or electron-beam irradiation.
For the coating it is possible as self-adhesive compositions to employ thermoplastic hotmelt adhesive compositions based on natural and synthetic rubbers and on other synthetic polymers such as acrylates, methacrylates, polyurethanes, polyolefins, polyvinyl derivatives, polyesters or silicones with corresponding additives such as tackifier resins, plasticizers, stabilizers and other auxiliaries where necessary.
Their softening point should be higher than 50xc2x0 C., since the temperature of application is generally at least 90xc2x0 C. and, preferably, between 120 and 150xc2x0 C., or between 180 and 220xc2x0 C. in the case of silicones. Postcrosslinking by means of UV or electron-beam irradiation may be appropriate, if desired.
Hotmelt adhesive compositions based on block copolymers, in particular, are notable for their diverse variation options, since the controlled reduction in the glass transition temperature of the self-adhesive composition as a result of the selection of the tackifiers, plasticizers, polymer molecule size and molecular distribution of the starting components ensures the required bonding, especially to the skin, in a manner appropriate to their function, even at critical points of the human locomotor system.
The high shear strength of the hotmelt adhesive composition is achieved through the high cohesiveness of the polymer. The good tack results from the range of tackifiers and plasticizers employed.
The hotmelt adhesive composition is based preferably on block copolymers, especially A-B or A-B-A block copolymers or mixtures thereof. The hard phase A is primarily polystyrene or its derivatives, and the soft phase B comprises ethylene, propylene, butylene, butadiene, isoprene or mixtures thereof, particular preference being given to ethylene and butylene or their mixtures.
However, polystyrene blocks may also be present in the soft phase B, in an amount of up to 20% by weight. The overall proportion of styrene, however, should always be less than 35% by weight. Preference is given to styrene contents of between 5 and 30%, since a lower styrene content makes the adhesive composition more conforming.
The controlled blending of diblock and triblock copolymers is particularly advantageous, preference being given to a proportion of diblock copolymers of less than 80% by weight.
In one advantageous embodiment the hotmelt adhesive composition has the following composition:
from 10 to 90% by weight of block copolymers,
from 5 to 80% by weight of tackifiers, such as oils, waxes, resins and/or mixtures thereof, preferably mixtures of resins and oils,
if desired, less than 60% by weight of plasticizers,
less than 15% by weight of additives,
less than 5% by weight of stabilizers.
The aliphatic or aromatic oils, waxes and resins used as tackifiers are preferably hydrocarbon oils, waxes and resins, the consistency of the oils, such as paraffinic hydrocarbon oils, or of the waxes, such as paraffinic hydrocarbon waxes, accounting for their favourable effect on bonding to the skin. Plasticizers used are medium- or long-chain fatty acids and/or their esters. These additions serve to establish the adhesion properties and the stability. If desired, further stabilizers and other auxiliaries are employed.
The adhesive composition can be filled with mineral fillers, fibres or hollow or solid microbeads.
The hotmelt self-adhesive composition has a softening point of more than 70xc2x0 C., preferably from 95 to 120xc2x0 C.
The hotmelt self-adhesive compositions are preferably formulated such that at a frequency of 0.1 rad/s they have a dynamic-complex glass transition temperature of less than 5xc2x0 C., preferably from xe2x88x923 to xe2x88x9230xc2x0 C. and, with very particular preference, from xe2x88x929 to xe2x88x9225xc2x0 C.
Medical products in particular are subject to stringent requirements in terms of their adhesion properties. For ideal application, the hotmelt adhesive composition should possess a high tack. There should be functionally appropriate bond strength to the skin and the reverse of the backing. So that there is no slipping, moreover, the hotmelt adhesive composition is required to have a high shear strength.
The controlled reduction in the glass transition temperature of the self-adhesive composition, which is essential to the invention and a consequence of the selection of the tackifiers, of the plasticizers and of the polymer molecule size and the molecular distribution of the starting components, achieves the required bonding, in a manner appropriate to its function, to the skin and to the reverse of the backing. The high shear strength of the self-adhesive composition employed here is achieved through the high cohesiveness of the block copolymer. The good tack arises from the range of tackifiers and plasticizers employed.
Product properties such as tack, glass transition temperature and shear stability can be quantified readily by means of a dynamomechanical frequency measurement. In this case, use is made of a rheometer controlled by shearing stress.
The results of this measurement method give information on the physical properties of a substance by taking into account the viscoelastic component. In this instance, at a preset temperature, the hotmelt self-adhesive composition is set in oscillation between two plane-parallel plates with variable frequencies and low deformation (linear viscoelastic region). Via a pickup control unit, with computer assistance, the quotient (Q=tan 6) between the loss modulus (Gxe2x80x3, viscous component) and the storage modulus (Gxe2x80x2, elastic component) is determined.
Q=tan xcex4=Gxe2x80x3/Gxe2x80x2
A high frequency is chosen for the subjective sensing of the tack and a low frequency for the shear strength.
A high numerical value denotes better tack and poorer shear stability.
The glass transition temperature is that temperature at which amorphous or partially crystallized polymers undergo transition from the liquid or rubber-elastic state into the hard-elastic or glassy state, or vice versa (Rxc3x6mpp Chemie-Lexikon, 9th Ed. Vol. 2, page 1587, Georg Thieme Verlag Stuttgartxe2x80x94New York, 1990). It corresponds to the maximum of the temperature function at a predetermined frequency.
For medical applications in particular, a relatively low glass transition point is required.
In accordance with the invention, preference is given to hotmelt adhesive components for which the ratio of the viscous component to the elastic component at a frequency of 100 rad/s and 25xc2x0 C. is greater than 0.7, preferably from 1.0 to 5.0, or to hotmelt self-adhesive compositions for which the ratio of the viscous component to the elastic component at a frequency of 0.1 rad/s and 25xc2x0 C. is less than 0.4, preferably between 0.35 and 0.02 and, with very particular preference, between 0.3 and 0.1.
It is also advantageous, especially for use in connection with medical products, if the hotmelt adhesive composition is applied partially to the backing material, by means for example of halftone printing, thermal screen printing, thermal flexographic printing or intaglio printing, because backing materials which have been adhesively treated in a continuous applied line may easily induce mechanical skin irritations when applied.
Partial application makes it possible to dissipate the transepidermal water loss through controlled channels and improves the removal of perspiration from the skin in vapour form, especially when the backing materials used are permeable to air and water vapour. This avoids skin irritations induced by buildup of body fluids. The dissipation channels that have been set up enable fluids to be conducted away, even when a multi-ply bandage is used.
In addition, in the case of backing materials with a high weight per unit area and low extension, as are common, for example, for short-term dressing, the partial coating actually enables redetachment by extension in a manner which, despite the high bond strength of these adhesive dressing systems, is extremely painless.
Preference is given to application in the form of polygeometric domes and, in particular, of those domes where the ratio of diameter to height is less than 5:1. Printed application of other forms and patterns on the backing material is also possiblexe2x80x94for example, a printed image in the form of alphanumeric character combinations or patterns such as matrices, stripes, assemblies of domes, and zigzag lines.
In addition, for example, the composition can be applied by spraying, so producing a more or less irregular applied pattern.
The self-adhesive composition can be distributed uniformly over the backing material; alternatively, it can be applied with a thickness or density which varies over the area, as appropriate to the function of the product.
The principle of thermal screen printing lies in the use of a rotating, heated, seamless, drum-shaped, perforated, cylindrical screen which is fed via a nozzle with the preferred hotmelt self-adhesive composition. A specially shaped nozzle lip (circular-gap or square-section coating bar) presses the hotmelt adhesive composition, which is fed in via a channel, through the perforation of the screen wall and onto the backing web that is conveyed past it. This backing web is guided by means of a counterpressure roller against the external jacket of the heated screen drum at a rate which corresponds to the peripheral speed of the rotating screen drum.
In this process, the formation of the small domes of adhesive takes place according to the following mechanism:
The pressure of the nozzle coating bar conveys the hotmelt adhesive composition through the screen perforation onto the backing material. The size of the domes formed is defined by the diameter of the screen perforation. The screen is lifted from the backing in accordance with the rate of transportation of the backing web (rotary speed of the screen drum). As a consequence of the high adhesion of the self-adhesive composition and of the internal cohesion of the hotmelt, the limited supply of hotmelt adhesive composition in the perforations is drawn in sharp definition from the base of the domes, which is already adhering to the backing, and is conveyed onto the backing by the pressure of the coating bar.
Following the end of this transportation, the more or less highly curved surface of the dome forms over the predefined base area in dependence on the rheology of the hotmelt adhesive composition. The height-to-base ratio of the dome depends on the ratio of perforation diameter to the wall thickness of the screen drum and on the physical properties (flow, surface tension and contact angle on the backing material) of the self-adhesive composition.
For the screen in thermal screen printing the web-to-hole ratio can be less than 3:1, preferably less than or equal to 1:1 and, in particular, equal to 1:3.
The above-described mechanism of formation of the domes requires, preferentially, backing materials that are absorbent or at least wettable by hotmelt adhesive composition. Non-wetting backing surfaces must be pretreated by chemical or physical methods. This can be done by means of additional measures such as corona discharge, for example, or by coating with substances which improve wetting.
Using the printing technique indicated it is possible to lay down the size and shape of the domes in a defined manner. The bond strength values which are relevant for use, i.e. those which determine the quality of the products formed, are within very narrow tolerances provided that coating is carried out correctly. The base diameter of the domes can be chosen to be from 10 to 5000 xcexcm, the height of the domes from 20 to about 2000 xcexcm and, preferably, from 50 to 1000 xcexcm, the low-diameter range being intended for smooth backings and the range of greater diameter and greater dome height being intended for rough or highly porous backing materials.
The positioning of the domes on the backing is laid down in a defined manner by the geometry of the applicator unit, for example the gravure or screen geometry, which can be varied within wide limits. With the aid of the parameters indicated it is possible by way of adjustable variables to establish with very great precision the desired profile of properties of the coating, harmonized with the various backing materials and applications.
The backing material is preferably coated at a rate of more than 2 m/min, preferably from 20 to 220 m/min, the chosen coating temperature being greater than the softening point.
The hotmelt adhesive composition can be applied to the backing material in a weight per unit area of more than 15 g/m2, preferably between 20 and 300 g/m2 and, with very particular preference, between 90 and 160 g/m2.
The percentage area which is coated with the hotmelt adhesive composition should be at least 20% and can extend up to approximately 95%, for specific products preferably from 40 to 60% and from 70 to 95%. This can be achieved if desired by means of multiple application, with the possible use if desired of hotmelt adhesive composition s having different properties.
It has also been found advantageous to load the adhesive with gas so as to improve the performance properties. In this way it is possible, for example, for better conformity and an increase in the initial bond strength to occur. It is preferred to load the hotmelt self-adhesive composition with a gas content of more than 5% by volume, preferably from 20 to 85% by volume.
The combination of the hotmelt adhesive composition and the partial coating firstly ensures secure bonding of the medical product to the skin and secondly rules out allergic or mechanical skin irritationsxe2x80x94at least those which are visually discerniblexe2x80x94in the case even of an application which extends over several days.
The epilation of corresponding body regions and the transfer of composition to the skin are negligible owing to the high cohesiveness of the adhesive, since the adhesive is not anchored to skin and hairxe2x80x94rather, the anchorage of the self-adhesive composition to the backing material, at up to 12 N/cm (sample width), is good for medical applications.
Because of the intended breakage points which have been formed in the coating, layers of skin are no longer displaced with one another or against one another in the course of detachment. The non-displacement of the layers of skin and the relatively low level of epilation lead to an unprecedented degree of painlessness in such strongly adhering systems. The applied backing material shows good proprioreceptive effects.
Depending on the backing material and its temperature sensitivity, the hotmelt adhesive composition can be applied directly or can be applied first to an auxiliary support and then transferred to the ultimate backing. Subsequent calandering of the coated product and/or pretreatment of the backing, such as corona irradiation, may be advantageous for better anchorage of the adhesive film.
The backing material coated with the adhesive coating composition can have an air permeability of greater than 1 cm3/(cm2*s), preferably greater than 15 cm3/(cm2*s) and, with very particular preference, greater than 70 cm3/(cm2*s) and a water vapour permeability of greater than 500 g/(M2*24h), preferably greater than 1000 g/(m2*24h), and, with very particular preference, greater than 2000 g/(m2*24h).
Following the coating operation, finally, the backing material can be lined with an anti-adhesive backing material, such as siliconized paper, or provided with a wound pad or padding.
It is particularly advantageous that the self-adhesively treated backing material can be sterilized, preferably by means of xcex3 (gamma) radiation. Consequently, particular suitability for subsequent sterilization is possessed by block copolymer-based hotmelt adhesive compositions which contain no double bonds. This applies in particular to styrene-butylene-ethylene-styrene block copolymers or styrene-butylene-styrene block copolymers. In this case the adhesive properties are not subject to any changes significant for the application.
Finally, the self-adhesive composition may comprise an active substance. In the case of doped self-adhesive compositions, particular preference is given to those which release substances.
The backing material of the invention has a bond strength to the reverse of the backing of at least 0.5 N/cm, in particular between 1 and 5 N/cm. Higher bond strengths may be achieved on other substrates.
The outstanding properties of the self-adhesively treated backing material of the invention suggest its use for medical products, especially plasters, medical fixings, wound coverings, orthopaedic or phlebological bandages, and dressings.

Self-adhesively treated backing material


Each output signal of programmable logic circuitry is made programmably available to drive one or more of a plurality of tri-statable input/output pins of the circuitry. Each output signal is also made programmably available to provide the output enable signal for one or more of a multiplicity of those input/output pins. The above-mentioned plurality and multiplicity associated with each output signal may include the same or different input/output pins. Output signals may therefore be routed to the input/output pins with greater flexibility, and output enable signal options are also greatly increased.

This invention relates to programmable logic circuitry, and more particularly to circuits for controlling tri-statable input/output ("I/O") terminals or "pins" in such circuitry.
Programmable logic circuitry is well known as shown, for example, by Wong et al. U.S. Pat. No. 4,871,930, Pedersen et al. U.S. Pat. No. 5,241,224, Cliff et al. U.S. Pat. No. 5,260,611, and Cliff et al. U.S. Pat. No. 5,689,195, all of which are hereby incorporated by reference herein. Such circuitry, which is generally implemented in integrated circuit devices, typically includes large numbers of input/output ("I/O") terminals or "pins." Each such I/O pin typically has a tri-statable output driver for selectively applying an output signal of the programmable logic to the I/O pin, generally so that this signal can be applied to circuitry external to the programmable logic. Thus the tri-statable output driver must receive both the output signal and a so-called output enable ("OE") signal for controlling the state of the driver. If the I/O pin is to be used as an input pin (through which the programmable logic can receive an input signal from external circuitry), the OE signal is switched to the state which causes the tri-statable output driver to block any signal from the programmable logic. In the output mode the OE signal may be used to control the timing with which the output signal is applied to the I/O pin. Thus the OE signal frequently plays an important role in relation to the associated output and/or input signals, and this role may differ for different uses of the programmable logic device or for different I/O pins of a given device.
In view of the foregoing, it is an object of this invention to provide improved circuitry for tri-statable I/O pins in programmable logic.
It is a more particular object of this invention to provide tri-statable I/O pin circuitry for programmable logic which has greater flexibility of use.

Tri-statable input/output circuitry for programmable logic


A clamping collar comprising: a belt having two free ends, at least one of said free ends being curved back to form a loop, said loop being defined by an outer belt portion and by an underlying inner belt portion; and a tightening system suitable for co-operating with said loop so as to tighten said belt; in which clamping collar said outer belt portion presents a pushed-in portion, set back relative to the outer outline of the loop, which pushed-in portion defines a tightening wall with which the tightening system comes into engagement, and is flanked on either side by respective ones of two edge segments of the outer belt portion.

The invention relates to a clamping collar.
Such a collar can be used to connect pipes, in particular in the automobile industry or in the aircraft industry (e.g. to connect pipes of the exhaust system or of the system for depolluting combustion gases).
More particularly, the invention relates to a clamping collar of the type comprising:                a belt having two free ends, at least one of said free ends being curved back to form a loop, said loop being defined by an outer belt portion and by an underlying inner belt portion; and        a tightening system suitable for co-operating with said loop so as to tighten said belt.
Generally, both of the free ends of said belt are curved back so as to form respective loops, and said tightening system makes it possible bring said loops closer together for tightening said belt.
A collar of this type is described in Document FR 2 522 086. That collar has a tightening system with two semi-cylindrical retaining pieces that are received inside respective ones of the two loops of the collar. Such retaining pieces can be referred to as "blocks" or as "gudgeons".
The first block is provided with a tapped through hole and the second block is provided with a smooth through hole. The tightening system further comprises a screw having a threaded shank and a screw head. Each loop of the collar is provided two openings that are in register with each other so that the shank of the screw passes through each of the two loops. In addition, the shank of the screw passes freely through the smooth hole and engages in the tapped hole. While the screw is being screwed into the first block, the screw head comes into engagement with the second block which then pushes against the inner belt portion of one loop, while the first block pushes against the inner belt portion of the other loop. The collar is thus tightened by bringing said loops closer together.

This patent is subject to a terminal disclaimer.