The invention describes, in combination, a pin and a pin holding device and discloses a method for electrically and mechanically connecting the stranded center conductor of a microcoaxial cable to the pin without the use of traditional soldering or crimping methods. The invention allows a cable installer to connect an end of a microcoaxial cable having a stranded center conductor to a male coaxial cable connector which requires a solid center conductor such as a pin for greatest reliability. The invention provides a stranded conductor to solid wire adaptor. In a preferred embodiment, the invention utilizes a twist-wirelock section to affix a stranded wire center conductor to a solid pin.

1. Field of the Invention
The present invention relates to coaxial cable connections, their implementation and use
2. Prior Art
In signal transmission applications, the choice of coaxial cable for conducting the signal is usually determined by the distance between connection points, the signal frequency, the maximum bend radius required, and the connector space available in a particular transmitting and/or receiving device. The longer the cable and the higher the frequency used, the larger the outside diameter needs to be to prevent excessive signal loss. Traditional coaxial cable applications such as Cable TV, Broadband data, and microwave signal transmission, employ coaxial cables with O.D.'s of 0.25-1 inches for distances of 50-1000 feet. In indoor equipment, the shorter distance requirements (typically 6-24 inches), the limitations of limited space and tighter bend radius requirements are overcome by using smaller coaxial cables with O.D.'s of 0.1-0.14 inches. These small OD cables typically require the use of precision micro-connectors such as SMA, SMB and MCX, which must be connected to the cable in a more or less controlled setting such as a laboratory with precise equipment to both hold and electrically attach the cable to the connectors. The central conductor for such microcoaxial cables is usually attached to the connector by either soldering directly to a fixed center pin in the connector, or soldering or crimping the central conductor to a separate small center pin which is then inserted into the connector. The soldering method requires both electricity and a clean, well lighted area for assembly. The use of small separate center pins, with a diameter of about 0.040 inch, need careful handing and holding during assembly. The installer needs to hold the pin, place it over the cable center conductor, and then perform the solder or crimp procedure.
With the increased demands on broadband network centers and field located hubs, there exists a need for higher density coaxial cable bundles having as many as 200 coaxial cables connected between equipment locations 100 feet apart. These new high-density cable assemblies now require field-installable connectors that are installed in lab environments. The high-density equipment backplanes also require microcoaxial cable connectors rather than larger connectors used when only a few low density cables are involved. The new cable requirements have been met with the development of lower loss microcoaxial cable bundles containing as many as 12 coaxial cables (each with a 0.1 in. OD) within in a 0.45 inch diameter jacket. There is a need for a reliable method of attaching these microcoaxial cable connectors to the microcoaxial cables in the field without the need for soldering and special handling equipment. A problem encountered during field installation of microcoaxial cable connectors is chemical contamination of conductive parts of the assembly from the installer's hands. Precision microcoaxial cable connectors are usually plated with gold to limit oxidation and thus require a level of cleanliness to insure proper performance. It is very difficult to insure this level of clean handling when the installer is required to manually grasp the connection center pin in the microcoaxial connector during installation.
Coaxial cables with larger center conductors of over 0.031 in. (0.8 mm) usually use the central conductor as the male center pin within the (assembled) male connector. The central conductor is then inserted directly into the female receptacle that comprises a mating seizing pin. Smaller cables require a male pin to first be attached to the (smaller) central conductor in order to confer the rigidity to the male pin needed to overcome the insertion force required for mating engagement with the female receptacle. Even with additional fixed center pins, the insertion force required for secure engagement can still be limited by the weaker section of the small central conductor not supported by the larger fixed pin.
Coaxial cable connector construction and installation is well known in the established art. The present inventor, in copending U.S. Pat. No. 6,217,383 discloses a compression-type coaxial cable connector. The connector, and each of the components associated therewith, has an axial conduit coextensive with the length thereof. When the prepared end of a coaxial cable is advanced through the conduit into the body portion, a shank separates the outer protective jacket and conductive braid of the cable from the dielectric core and interposes the barbed portion of the tubular shank therebetween. A compression sleeve, with the assistance of a compression tool, compresses the cable jacket and braid providing secure attachment.
Stirling, in U.S. Pat. No. 5,007,861, discloses a crimpless coaxial cable connector which can be secured to a cable simply by pushing the cable into the connector and subsequently pulling it back. The body of the connector has a bushing mounted within it near the cable-receiving end having a conduit dimensioned to receive the cable. The body of the connector also has within it an annular mandrel having a bore to receive the stripped core of the cable, and having a sleeve adapted to engage the cable beneath the jacket by pushing the cable and the mandrel together.
Another radial compression type of coaxial cable connector of the type generally used today for forming an electrical connection between a central conductor within the coaxial cable and a mating fixture is described in detail in U.S. Pat. No. 5,632,651 to Szegda. Various other coaxial cable connectors adapted to from a secure, electrically conductive connection between a coaxial cable and a threaded female port have been developed. Such prior art connectors are discussed, for example, in U.S. Pat. No. 5,024,606 to Ming-Hua, U.S. Pat. No. 4,280,749 to Hemmer, U.S. Pat. No. 4,593,964 to Forney, Jr. et al., U.S. Pat. No. 5,073,129 to Szegda and U.S. Pat. No. 5,651,699 to Holliday. U.S. Pat. No. 5,879,191 to Burris, discusses prior art efforts to provide a coaxial connector which is moisture-proof and minimizes radiative loss of signal from the cable.
All of the above-referenced connectors require that a stripped length of the coaxial cable' central conductor project from the end of the cable within the axial bore in the connector for engagement with a conductive receptacle in the mating fixture. The prior art connectors work well with standard coaxial cables having a relatively large gauge central conductor because the stripped length is rigid. The rigid conductor can be forced into a spring receptacle in a mating fixture without difficulty. Microcoaxial cables, however, have a small, fragile central conductor. The stripped length of the central conductor in a microcoaxial cable lacks the structural integrity for insertion into a conductive receptacle in a mating fixture. It is current practice to solder or crimp an electrically conductive cap over the stripped length of central conductor in order to provide sufficient rigidity to the central conductor for use with standard connector assemblies.
The present inventor, in U.S. Pat. No. 6,361,364, discloses a method of electrically and mechanically connecting the center conductor of a micro-coaxial RF cable to a coaxial cable connector or bulkhead without the use of traditional soldering or precision tools. The device is essentially a solderless, crimpless connector. The invention allows a cable installer to connect a micro-coaxial cable having a central conductor as small #30 AWG (0.25 mm) to a coaxial cable connector under field conditions. The invention employs a two-stage, spring loaded center pin holding device and a method for using the device to facilitate easy field installation while maintaining mechanical and electrical reliability.
It has become popular to use a stranded center conductor for coaxial microcables to add greater flexibility and prevention of the solid micro center conductor from breaking due to bending. An equivalent #26 stranded wire might consist of 5 #36 conductors which creates an even greater need for a solid pin adaptor for insertion into the connector.
The prior art consists of four methods of attaching a stranded center conductor of a coaxial cable to a coaxial connector. The first is crimping or soldering an external pin attached to a crimp or solder cap. This method has been used for larger conductors, typically #16-20 gauge wire. This, as mentioned earlier, is not effective for coaxial microcables in that the soldering may melt the other plastic components of the cable and is difficult to perform except in laboratory conditions. Crimping requires the precision of a magnified view and special tools. The crimp cap must also be able to compress to an effective range to hold the microstranded wires. This is easy with larger wires where the larger caps' wall thickness can provide the needed strength upon compression
The second prior art method is to blindly insert the stranded wire into the entire connector assembly trying to guide the flexible wire into an open hole of cylindrical seizing pin. Upon compressing or crimping of the entire connector assembly, a sliding tapered outer cylindrical member squeezes the seizing pin down on the stranded wire. The problem with this method is that the flexible stranded wire center conductor of a microcable (smaller than #22 gauge) does not have the structural ability to move into the connector any distance without bending and bunching up; resulting in the conductor never entering the connector's center conductor seizing pin. The ability to insure a tight mechanical and electrical connection to the stranded micro center conductor prior to insertion into the connector assembly is needed for high reliability performance.
The third prior art method consists of a variation of the prior method, having an internal cylindrical open seizing clamp inside the connector body. The stranded center coaxial cable is inserted into the open cylindrical seizing pin which then is intended to be pushed inward through a tapered hole until the taper compresses the seizing pin to hold the stranded wire securely. To accomplish this inward movement of the seizing pin through the tapered hole, the cable is used as the axial force tool by pushing inward. The problem with this method is that it can only work effectively if the cable is rigid and will not bend upon the axial force needed to drive the clamp tube through the taper. This method has worked with coaxial cables having a minimum outside diameter of 6.5 mm and typically 12 mm. In that the micro coaxial cables intended for this invention may have an O.D. ranging from 2-5 mm, and limited axial force capability, the mentioned prior art will not work. A second reason for this methods' failure is that the inward moving pin/clamp tube must lock into a notch to prevent later retraction of the cable and center pin from loosening around the stranded center wire. The user cannot always be sure they have engaged this locking notch due to the difficulty of knowing how far to insert the cable. One additional reason for this external stranded-to-solid pin adaptor is to give the user the ability to insure the stranded conductors are secure in the new fixed pin.
The forth prior art method consists of inserting the stranded wire into a flat seizing pin which allows the wire to push open the contact and be held based upon the spring retention of the spring clamping pins. This method relies upon the rigidity of the stranded wire to open up the clamp without bending.
Due to the fragile nature of stranded conductors, the above-referenced devices and methods are not suitable for connecting the stranded center conductor of a coaxial microcable to a coaxial cable connector. Crimp methods of securing an adaptor pin used in solid wire cables will only work with larger solid cables and will not work well for a micro stranded wire due to the difficulty in using a tool in non-laboratory conditions. A method and device is needed to attach a larger diameter pin (typically 1 mm o.d.) over a stranded wire having an outer diameter of 0.45 mm. Accordingly, there is a current need for a solderless device and method for adapting the stranded central conductor of a microcoaxial cable for use with standard coaxial cable connectors without the need for soldering or precision crimping.

Tool operable for attaching a solid pin to a stranded wire


The invention relates to a device for applying flowing media to a surface. Said device comprises a container (1) for the media with at least one opening (2, 3) which is located above the surface and can be deaerated and a mopping or applicator device (5) which is attached to a handle (4). In addition, the device has a flow-regulating hose (6) which can be shut off, for conveying the media from the container (1) by force of gravity to an outlet on the mopping or applicator device (5). In addition, the device has a portable unit which is worn on the back, comprising supporting and fixing straps (8) and a mounting plate (9) which is fitted to said unit and which has a rapid-action coupling device. The container has (1) a resealable exit opening at one end (2) with a connecting sleeve and a resealable fill opening (3) at the opposite end, in addition to a hose adapter (11) which can be connected to the connecting sleeve of the exit opening (2). Said adapter has a shut-off device (12) and a rapid-action coupling (13) for the hose with a drip-protection unit.

The invention relates to a device for applying flowable media to a surface, comprising a ventilatable container, which is arranged above the surface, for the media, with at least one opening, a wiping or applying device mounted at a handle and a duct, which can be regulated for shutting off and allowing throughflow, for the gravitationally-effected conducting of the media from the container to an outlet on or at the wiping or applying device.
In the state of the art, in the case of cleaning and care activities the cleaning, disinfecting or care agent is tipped directly from a corresponding product cask directly onto the preferably smooth, flat or slightly inclined surface, for example the floor. The agent can, however, also be diluted in a container and tipped onto the floor as a diluted solution ready for use. A dispersion coating is briefly described here, by way of example, for the previous procedure.
For the tipping-on the dispersion the worker has to bend deeply in constant succession in order to pour the dispersion onto the floor and has to significantly incline the upper body forwards and at the same time turn in order to uniformly distribute the product. In this procedure only a part area of the surface can be processed until the poured-on quantity has been dealt with. This work is also frequently undertaken by two persons, one of which tips the dispersion onto the respective area to be processed and the other of which uniformly distributes the dispersion. In all cases there is a continual, time-consuming and tiring alternation between the two different working processes. A continuous working, which is an essential precondition for an even quality of the coating, is not possible in that case. In the state of the art applicator devices are known in which the media are placed under pressure in the containers and conducted out of the container. In that case the throughflow quantity and the flow speed is influenced and is reduced in the case of pressure drop in the container, so that a longer term, continuous and uniform working free of start point is not possible.
In the state of the art devices as described in the introduction are also known, for example in DE 39 05 760 A1. In that case the containers are mounted at the handle of the wiping or applying device. It is indeed thereby possible to reduce at least a part of the difficulties of the described procedure. However, the handling of the wiping or applying device is at the same time made quite significantly difficult, as the mounting of the container at the manipulating handle causes very unfavourable and constantly changing centre-of-gravity relationships. Moreover, in the case of this mounting the size and the shape of the container is strongly limited or restricted and the exchange and subsequent filling or refilling of the container is very inconvenient and made difficult, so that the use of commercially available casks is hardly possible or possible only with much difficulty.
The invention is based on the technical problem of so developing the device described in the introduction that the disadvantages are avoided and in simple and economic manner there is created a device enabling a continuous working of largest possible areas.
This problem is solved in that the device described in the introduction comprises equipment, which can be worn on the back, with supporting and fixing straps and a mounting plate, which is fixed thereto, with a quick-action coupling device and the container has at one end a resealable outlet opening with a connecting piece and a resealable filling opening at an opposite end, as well as a hose adapter, which is connectible to the connecting piece of the outlet opening, with a shut-off device and a hose quick-action coupling with a drip protection device.
This device has the advantage that even larger quantities of the flowable media to be applied can be carried by the operator, as its arrangement on the back of the operator does not obstruct or impair the work during application and even larger areas can thereby be processed by an operator continuously and free of start point. Moreover, it is of advantage that the container can be subsequently filled or refilled in simple manner without the hose adapter having to be removed from the outlet opening for that purpose. In addition, in advantageous manner it is possible at the conclusion of a working phase to leave the rest of the unconsumed medium in the container if the outlet opening is closed by a closure lid after removal of the hose adap ter.
Two different container types can be used in the proposed device. For this purpose in a special embodiment the container comprises coupling elements which are matched to the quick-action coupling device of the mounting plate. In another embodiment the coupling elements, which are matched to the quick-action coupling device of the mounting plate, are provided at a cask receiver. Commercially available product casks can be inserted into this cask receiver and thus carried on the back of the operator with the assistance of the cask receiver. If the container has the coupling elements, then this is suitable as a universal container into which the appropriate media can be poured from commercially available product casks.
An embodiment in which the hose adapter comprises a closure system, for example a screw or bayonet closure, matched to the connecting piece of the outlet opening is particularly advantageous. With advantage, the closure system is so constructed that it is matched to the closure of commercially available casks, so that the same hose adapter can be placed not only on the outlet opening of the universal container, but also on the outlet opening of the product cask. Advantageously the hose adapter has a ventilating element so that the container does not need a separate venting device for pressure equalisation and the container at the end of the working process and after removal of the hose adapter can be directly closed again by the closure cap in the pressure-equalised state.
In an advantageous embodiment the universal container has a filling opening which in shape and/or size is suitable for the pouring in of the media without a funnel or similar means and is closable by a closure lid. It is thereby possible to refill the medium, after consumption of the quantity originally poured in, without the container having to be exchanged or the hose adapter or the duct having to be removed for conveying the medium to the duct outlet. Since the universal container and cask receptacle both have identical coupling elements matched to the quick-action coupling device of the mounting plate, it is in addition possible to quickly and simply exchange the universal container for a cask receiver with a commercially available product cask, and vice versa.
In a special embodiment the universal container has a filling state marking indicating the filling state for a solvent, for example water, wherein the solvent quantity corresponding to this filling state is to be dimensioned so that it guarantees by a predetermined concentrate quantity the concentration or dilution prescribed and advantageous for the respective medium. It is thereby possible that the operator, for example for water-soluble concentrate, has to carry only the appropriate concentrate basic quantity in a dosage cartridge or other such dosage container and can then prepare a new container charge in the desired concentration at each water connection point present at the property to be treated. If the refill cartridge or other dosage container has a special closure, a special connecting device for this closure is conveniently provided in the closure cover of the filling opening.
So that the product or medium, on outflow from the duct outlet does not spray at too great a drop height or clash with the wiping or applying device at too small a spacing from the surface to be treated, the outlet opening is arranged above the surface at a spacing matched to the product or medium and the consistency thereof.
The metering valve for throughflow regulation of the product is advantageously arranged between hose quick-action coupling and the outlet of the duct on or at the wiping or applying device, so that after removal of the duct or the hose from the hose adapter the quantity disposed in the duct can still be applied at the desired throughflow rate. In that case it is advantageous if the hose quick-action coupling has a drip protection, which closes the connection to the container in, for example, spring-loaded manner or by a ball or other such, so that even without actuation of the shut-off device no product can continue to flow out of the container after removal of the hose and/or the duct.
The proposed device enables a simple and ergonomically favourable handling for a widespread spectrum of use with high area performance and low consumption of product/media. Product loss is largely avoided, as commercially available product casks can be used and in the case of cask exchange or cleaning of the device only small product residues (waste) occur, since the product residues can usually remain in the closed cask.


This invention relates to a pierceable sealing element for a liquid outlet, especially an ink outlet opening of an ink reservoir in inkjet printing means, and an ink reservoir with one such sealing element which has a membrane which can be pierced by a hollow needle for removing liquid, and the hollow needle can be surrounded sealed from the outside by the pierced seal element. To form an improved seal with low production and installation cost it is proposed as claimed in the invention that the membrane is surrounded by an annularly peripheral sealing profile which can be twisted in the manner of a torus at least partially around a peripheral line when the membrane has been pierced, a sealing surface which runs radially on the inside being formed.

This invention relates to a pierceable sealing element for a liquid outlet, especially the ink outlet opening of an ink reservoir in inkjet printing means, which has a piercing area which can be pierced by a hollow needle for removing liquid, and the hollow needle can be surrounded sealed from the outside by the pierced seal element. An ink reservoir for detachable mounting in inkjet printing means with an ink outlet opening which is sealed by one such pierceable sealing element is likewise the subject matter of the invention.
To remove liquid as necessary, for example from an ink reservoir, sealing liquid-tight the outlet or removal opening with a closed sealing element which is intact before use is known. The liquid can be removed by means of a hollow needle which is plunged from the outside into the filled reservoir interior through the piercing area of the sealing element intended for this purpose. These sealing elements are used preferably in inkjet printing systems where the interchangeable ink reservoirs, the so-called ink cartridges, are first sealed on their ink outlet opening with one such pierceable sealing element after filling with ink during manufacture. The inkjet printer has a corresponding hollow needle which pierces the sealing element when the ink cartridge is being used and the ink contained in the ink cartridge can be supplied to the print head.
The important advantage of a pierceable sealing element is that it is sealed tight before the first use, i.e. the first perforation by the hollow needle, so that the liquid contained in the reservoir can neither emerge uncontrolled from the liquid outlet nor evaporate. Especially in ink cartridges is this particularly important since after production and filling with ink in general they are only used after some time. Even when stored for a longer time it must be ensured that neither the ink fill level is reduced nor the consistency of the ink adversely changed by vaporization.
One possibility for implementing a pierceable sealing element consists in the attachment of a liquid-tight and vapor-tight sealing film from the outside on the outlet opening. So that it can be easily pierced, i.e. clears the outlet when the generally relatively blunt hollow needle is plunged through, this sealing film consists of thin, relatively poorly elastic plastic material. In this way, when the piercing area is punctured it is completely ruptured and clears the outlet cross section. One such sealing film however does not perform a sealing function so that in the sealing element there must be additional sealing rings which seal against the outside periphery of the hollow needle so that liquid cannot emerge there uncontrolled along the hollow needle. These arrangements, as are described for example in EP 1 000 753 A1, are relatively complex due to the separate sealing elements.
A less complex version of a pierceable seal is a so-called septum. It has a relatively thick piercing area of rubber or thermoplastic elastomer. This piercing area bursts when the hollow needle is inserted, not over its entire surface in an uncontrolled manner, like a sealing film, but is essentially penetrated only in the cross sectional area of the hollow needle. Due to the elasticity of the rubber or elastomer material, the boundary surface of the puncture channel formed in doing so is pressed against the outside periphery of the hollow needle so that a certain sealing is achieved without additional sealing elements. Moreover when the hollow needle is removed the puncture channel is automatically reclosed. But when examined minutely, it is found that when the hollow needle punctures, the material of the septum is not radially displaced in a uniform manner, but a small lengthwise tear forms. In the area of the ends of the tear however along the puncture channel between the material of the septum and the outside periphery of the hollow needle gusset-like passages are formed. For this reason leaks are inevitable, especially when there is liquid in the container for a longer time, on the septum, as is the case in an inkjet printing systems. Likewise attempts have already been made to mold a piercing area with a reduced material thickness into the septum. But the results are however likewise not completely satisfactory since the seal can likewise be adversely affected by the irregular tear edges in the penetration channel.
In view of the aforementioned problems in the prior art, the motivation for the invention is to make available a pierceable sealing arrangement and an ink reservoir with one such sealing arrangement which has improved functionality with respect to the indicated problems. In particular, sealing to the hollow needle which is improved compared to a septum will be achieved and the production and installation cost will be as low as possible, especially less than in a multi-part arrangement with seals and a separate sealing film.
To solve the aforementioned problem as claimed in the invention an ink reservoir with a pierceable sealing element and a pierceable sealing element of the initially mentioned type are proposed in which the piercing area is surrounded by an annularly peripheral sealing profile which can be twisted in the manner of a torus at least partially around a peripheral line when the piercing area has been pierced, a sealing surface which runs radially on the inside being formed.
As claimed in the invention a novel sealing element is made available which has clearly distinguishable operating areas in one component. One particular feature compared to the prior art consists in that the two functions, specifically on the one hand the sealing function by a piercing area which can be ripped open only if necessary and on the other hand the sealing function with respect to the hollow needle in the penetrated state, are implemented by a functionally connected arrangement of the central piercing area with a special sealing profile which is formed or activated only when pierced.
In the initial state, before the sealing element has been pierced by a hollow needle, the piercing area extends for example in the form of a thin membrane over the opening cross section of an annular sealing profile which is inserted for its part tightly into the outlet opening, for example the ink outlet opening of an ink cartridge for an inkjet printing means. If from the outside a hollow needle is plunged into the piercing area, it tears or bursts so that the liquid outlet is cleared for example for ink removal through the hollow needle.
As was detailed initially, it can be assumed that the piercing channel or the tear edges of the piercing area at best provide for unsatisfactory sealing of the hollow needle in the outlet opening. The special advantage of the invention at this point consists in that when the piercing area is ripped open and with the associated radial bending-up of the separate parts of the piercing area which are connected in their outer edge areas to the sealing profile which runs peripherally there, the sealing profile is cleared and activated for sealing of the hollow needle. To do this, the sealing profile as claimed in the invention is actively manipulated by its being ripped open, i.e. the piercing of the piercing area, such that it is twisted toroidally on its inner periphery in the puncture direction of the hollow needle, i.e. that the surface areas of the sealing profile which are outside with respect to the puncture direction are swivelling radially to the inside in the direction of the pierced opening in an arc-shaped swivelling motion. In this way the actuation or formation of the sealing profile takes place such that annular surface areas of the sealing profile which are initially farther to the outside are swivelled to the inside, by which a defined sealing surface which runs radially to the inside is formed. This surface can uniformly adjoin the surface of the inserted hollow needle over the periphery. Because this sealing surface is a defined surface area which is uniformly smooth especially over its periphery, the sealing of the hollow needle is especially good. Due to the toroidal connection, moreover the edge areas of the piercing area which are separated from one another are swivelled away axially from this active sealing surface of the sealing profile so that they cannot adversely affect the sealing. This avoids the adverse effect which is occasionally observed in a combination of sealing films with sealing rings, specifically the remainder of the sealing film is retracted between the seal and the hollow needle upon puncturing. As a result of the clear functional connection of the piercing area to the peripheral sealing profile as claimed in the invention these disadvantages are effectively avoided.
The sealing element as claimed in the invention thus combines the advantages of a simple septum, specifically production and installation with low cost, with the advantages of a pierceable sealing film over a separate sealing arrangement, specifically the preparation of defined radial sealing surfaces for sealing the hollow needle. This improved functionality results first of all in that the deformations which occur when the piercing area is pierced and the associated forces are converted in a controlled manner into active manipulation or formation of the sealing profile. When the piercing area is pierced an optimized sealing arrangement is essentially automatically formed.
The sealing profile as claimed in the invention is preferably made as a sealing bead. The latter is formed by a notch which is trough-shaped in cross section and which runs annularly peripherally. This sealing bead is preferably axially opened to the inside with respect to the puncture direction. From the outside, therefore from the puncture side, the sealing bead thus forms a projecting sealing bulge.
The sealing bead is arranged such that the piercing area is connected to the inside edge of the sealing bead which is connected on its outside edge to the mounting element. This mounting element can be made as a tube section which can be fixed in the outlet opening. For example, one such sleeve-shaped mounting element can be inserted into the likewise tubular ink outlet of an ink reservoir and fixed therein.
In the above described embodiment, the sealing bead after splitting the piercing area when the hollow needle on its inner edge is inserted is bent moreover radially to the outside and drawn in the puncture direction by the arising friction forces of the suspended remainders of the piercing area. In this way the arched bottom area of the bead is twisted toroidally. In particular the sealing bead with the U-shaped cross section assumes the shape of an O ring on its inner periphery. Due to the swivelling and pulling motion of the split parts of the piercing area it is narrowed so that an especially internal opening cross section of this O ring-like seal yields moreover good radial sealing of the inserted hollow needle.
One especially advantageous embodiment of the invention as an alternative to the above described sealing bead calls for the sealing profile to be made as a sealing ring. Before the first use, i.e. before the first insertion of the hollow needle, the through opening of this sealing ring is sealed by the piercing area. This piercing area is made as a membrane-like, thin film which is connected to the inside edge of the sealing ring and has a smaller material thickness than the profile cross section of the sealing ring. The function and the resulting advantages of the sealing ring correspond essentially to the sealing bead. Upon piercing, first the puncture area is split by the hollow needle so that the through opening of the sealing ring is cleared. The friction forces acting upon axial insertion between the outside periphery of the inserted hollow needle and the inside periphery of the sealing ring twist this sealing ring around a peripheral line in the shape of a torus. This results in that the inside periphery, where the piercing area is connected to the sealing ring, is turned away from the surface of the inserted hollow needle, while moreover a peripheral sealing area is swivelled to the inside, surrounding the hollow needle tightly on the outside.
To achieve the aforementioned effect, the inside diameter of the sealing ring which is sealed first with the piercing area is chosen to be somewhat smaller than the outside diameter of the hollow needle. In this way, on the one hand it is ensured that the friction forces between the hollow needle and the sealing ring are large enough during puncture to twist the sealing ring around the peripheral line in the shape of a torus. On the other hand, the sealing ring consisting of rubber elastic material in the punctured state under radial pretensioning adjoins the hollow needle; this benefits good sealing action.
The sealing ring can have a round, preferably circular cross section. With the circular cross sectional profile a torus shape arises which corresponds to a classical O ring which can in the conventional manner adjoin a peripheral linear sealing surface on the hollow needle to form a good seal. In an individual case it can furthermore be advantageous for the sealing ring to have a rounded shape which deviates from the circular, for example an involute shape. In this way for example defined force ratios can be achieved between the hollow needle and the sealing ring upon puncture and after toroidal rerolling in the sealing state.
The sealing ring can moreover be connected via a peripheral, thin crosspiece to a mounting element. The mounting element is for example, as in the sealing bead, a tubular section, with the sealing element as claimed in the invention molded in one piece into its through cross section. The externally peripheral crosspiece is clearly thinner than the profile cross section of the sealing ring. In this way it can be swivelled easily when the hollow needle is inserted around a peripheral line which lies in the area of this thin crosspiece for executing the toroidal twisting as claimed in the invention.
In the version with the sealing ring the sealing profile can be made symmetrical with respect to the piercing plane. This piercing plane is defined by the piercing area. There is mirror symmetry to this surface when the sealing profile is made as an O ring with a circular profile cross section, the attachment to the mounting element taking place on the outer peripheral line and the piercing area being peripherally connected to the inside edge of the sealing ring. The symmetrical arrangement has advantages in production engineering. Moreover, installation is simplified thereby.
The piercing area can be made as a thin membrane with a smaller material thickness than that of the sealing profile or the sealing bead. Alternatively, the piercing area can have essentially the same material thickness as in the area of the sealing bead, but then can be provided with molded-in scored areas with a reduced material thickness. They are made for example as notches arranged in a line or cross-shape.
Preferably the connecting area between the piercing area and the sealing profile has a reduced material thickness. In this way, a type of annularly peripheral film hinge is formed which ensures that the separated areas of the sealing area when the hollow needle is inserted in the insertion direction are swivelled away from the sealing area of the sealing profile without the sealing profile being deformed in an uncontrolled manner.
Preferably the sealing element is produced from elastic material, such as natural or synthetic rubber materials or thermoplastic elastomers. But preferably the piercing area, the sealing element and the mounting element are made in one piece with one another. In this way not only simple and economical production, but also installation with low cost is enabled.

Pierceable sealing element and ink reservoir with pierceable sealing element

Artech GmbH Design + Production in Plastic


A fastener assembly comprises a first cylindrical member disposed within a second cylindrical member. One of the first and second cylindrical members is movable relative to the other in a first direction. The other one of the first and second cylindrical members is locked relative to the one in a second direction opposite to the first direction. A spring is operably attached to the first and second cylindrical members to urge one of the first and second cylindrical members in the first direction. A removable member is operably associated with the first and second cylindrical members to prevent one of the first and second cylindrical members from moving in the first direction prior to removing the removable member. The removable member is configured to be pulled out to allow one of the first and second cylindrical members to move in the first direction.

Prior art hold down systems, such as one disclosed in U.S. Pat. No. 6,951,078, typically use a tie-rod that extends inside a stud wall from the foundation to the top floor. Field conditions and the quality of the installer are such that the tie-rod may not be installed perpendicular to the cross or bridge member to which the tie-rod is to be secured. In such a situation, the bearing surface of the bridge member and the hold down device may not align properly for good bearing contact due to the out-of vertical position of the tie-rod. The resulting installation may not be satisfactory since full contact between bearing surfaces of the various components of the system is not achieved, thereby compromising the integrity of the system.
Another problem encountered with prior art hold down devices is that sometimes the installer forgets to activate the device after installation. The problem is sometimes discovered after the wall has been closed, thus causing a lot of expense to correct the problem.
Yet another problem with prior art device is the need of using a tool to load the spring in a hold down device. When a hold down device comes preloaded from the factory, and an installer accidentally releases the lock and allows the compressed spring inside to expand, to reset the spring would typically require a tool which may not be available to the installer.


Disclosed is a method of determining the extent of recovery of materials injected into a oil well comprising the steps of: a) preparing a material to be injected into an oil well; b) admixing therewith a chemical tracer compound at a predetermined concentration; c) injecting the admixture into an oil well; d) recovering from the oil well a production fluid; e) analyzing the production fluid for the concentration of the chemical tracer present in the production fluid; and f) calculating the amount of admixture recovered from the oil well using the concentration of the chemical tracer present in the production fluid as a basis for the calculation. Fluorinated benzoic acids are disclosed as a preferred tracer.

1. Field of the Invention
The present invention relates to a method for determining the extent of recovery of materials injected into an oil well during oil and gas exploration and production. The present invention particularly relates to a method for determining the extent of recovery of materials injected into an oil well during oil and gas exploration and production using chemical tracers.
2. Background of the Art
The present Invention relates generally to hydrocarbon (oil and gas) production from wells drilled in the earth, hereinafter referred to as xe2x80x9coil wells.xe2x80x9d Drilling a hole into the earth to reach oil and gas bearing formations is expensive which limits the number of wells that can be economically drilled. It follows then that it is desirable to maximize both and the overall recovery of hydrocarbon held in the formation and the rate of flow from the subsurface formation to the surface, where it can be recovered.
One way in which to maximize production is the process known as fracturing. Hydraulic fracturing involves literally breaking or fracturing a portion of the hydrocarbon bearing formation surrounding an oil well by injecting a specialized fluid into the wellbore directed at the face of the geologic formation at pressures sufficient to initiate and/or extend a fracture in the formation. Ideally, what this process creates is not a single fracture, but a fracture zone, i.e., a zone having multiple fractures, or cracks in the formation, through which hydrocarbon can more readily flow to the wellbore.
Creating a fracture in a hydrocarbon-bearing formation requires several materials. Often these materials, if not removed from the oil well, can interfere with oil and gas production. Even the drilling mud used to lubricate a drill bit during the drilling of an oil well can interfere with oil and gas production. Taking too long to remove such materials can increase the cost to the operator of the well by delaying production and causing excess removal expenses. Not being thorough in removing such materials can increase the cost to the operator of the well through lower production rates and possible lost production.
Measures taken to remove unwanted or unneeded materials are usually inexact. Sometimes additional fluids are used to flush out unwanted materials in the well bore. In other situations, reservoir fluids flow can make estimating return flow very difficult, particularly if the reservoir fluids are incompatible with the injected materials. It would be desirable in the art of oil and gas production to be able to determine how much of a given material is left in an oil well after a drilling, fracturing or any other operation requiring the injection of materials into an oil well. It would be particularly desirable if such a determination could be made using an inexpensive and environmentally benign method.
In one aspect, the present invention is a method for determining the extent of recovery of materials injected into a oil well comprising the steps of: a) preparing a material to be injected into an oil well; b) admixing therewith a chemical tracer compound at a predetermined concentration; c) injecting the admixture into an oil well; d) recovering from the oil well a production fluid; e) analyzing the production fluid for the concentration of the chemical tracer present in the production fluid; and f) calculating the amount of admixture recovered from the oil well using the concentration of the chemical tracer present in the production fluid as a basis for the calculation.
As already defined, the term xe2x80x9coil wellxe2x80x9d means hydrocarbon (oil and gas) production wells drilled in the earth. The method of the present invention can also be used with other types of wells that are drilled in the earth and can require stimulation by hydraulic fracturing, such as a well used for water flooding in secondary recovery operations in oil and gas production. For the purposes of the present invention, the term xe2x80x9coil wellxe2x80x9d means hydrocarbon production wells, but also any other type of well that can require stimulation by hydraulic fracturing.
In one embodiment, the present invention is a method for determining the amount of fracture materials recovered after the stimulation of an oil well by means of hydraulic fracturing. Creating a fracture in a hydrocarbon-bearing formation requires several materials. Most often these include a carrier fluid, a viscosifier, a proppant, and a breaker. Other components that are sometimes added include materials to control leak-off, or migration of the fluid into the fracture face, gel stabilizers, surfactants, clay control agents and crosslinkers.
The purpose of the first fracturing component is to first create/extend a fracture in an oil and gas producing formation and then, once it is opened enough, to deliver proppant. The carrier fluid together with proppant material is injected into the fractured formation. The carrier fluid is simply the means by which the proppant and breaker are carried into the formation.
Numerous substances can act as a suitable carrier fluid, though they are generally aqueous-based solutions that have been either gelled or foamed or both. Thus, the carrier fluid is often prepared by blending a polymeric gelling agent with an aqueous solution although sometimes the carrier fluid is oil-based or a multi-phase fluid. Often, the polymeric gelling agent is a solvatable polysaccharide, e.g., galactomannan gums, glycomannan gums, and cellulose derivatives. The purpose of the solvatable or hydratable polysaccharides is to thicken the aqueous solution so proppant can be suspended in the solution for delivery into the fracture.
The polysaccharides function as viscosifiers, increasing the viscosity of the aqueous solution by 10 to 100 times, or even more. During high temperature applications, a cross-linking agent is further added which further increases the viscosity of the solution. The borate ion has been used extensively as a crosslinking agent for hydrated guar gums and other galactomannans to form aqueous gels, e.g., U.S. Pat. No. 3,059,909. Other demonstrably suitable cross-linking agents include: titanium as disclosed in U.S. Pat. No. 3,888,312, chromium, iron, aluminum, and zirconium as disclosed in U.S. Pat. No. 3,301,723. More recently, viscoelastic surfactants have been developed which obviates the need for thickening agents, and hence cross-linking agents.
Most relevant to the present invention is the final step of the fracturing process. The process of removing the fluid from the fracture once the proppant has been delivered is referred to as xe2x80x9cfracture clean-up.xe2x80x9d For this, the final component of the fracture fluid becomes relevant: the breaker. The purpose of the breaker is to lower the viscosity of the fluid so that it is more easily removed from the fracture.
In another aspect, the present invention is a method for determining the amount of drilling fluid recovered after the completion of an oil well. A drilling fluid is a fluid specially designed to be circulated through a wellbore as the wellbore is being drilled to facilitate the drilling operation. The circulation path of the drilling fluid typically extends from the wellhead down through the drill pipe string to the drilling face and back up through the annular space between the drill pipe string and wellbore face to the wellhead. The drilling fluid performs a number of functions as it circulates through the wellbore including cooling and lubricating the drill bit, removing drill cuttings from the wellbore, aiding in support of the drill pipe and drill bit, and providing a hydrostatic head to maintain the integrity of the wellbore walls and prevent well blowouts.
There are a number of different types of conventional drilling fluids including compositions termed xe2x80x9cdrilling muds.xe2x80x9d Drilling muds comprise high-density dispersions of fine solids in an aqueous liquid or a hydrocarbon liquid. An exemplary drilling mud is a dispersion of clay and/or gypsum in water. The solid component of such a dispersion is termed a xe2x80x9cweighting agentxe2x80x9d and is designed to enhance the functional performance of the drilling fluid.
In the practice of the present invention, the extent of recovery of materials injected into a oil well during fracturing, drilling and the like is determined by preparing the fracture materials or drilling fluids to be injected into an oil well and admixing therewith a chemical tracer compound at a predetermined concentration. The tracers useful with the present invention include any known to those ordinary skill in the art of using chemical tracers in oil and gas operations to be useful, but preferably are those which can be detected at concentrations low enough to make their use economically practical in such operations and low enough to interfere with the carrier fluid or other materials present in the oil well. Preferably the chemical tracers useful with the present invention include but are not limited to: fluorinated benzoic acids including 2-fluorobenzoic acid; 3-fluorobenzoic acid; 4-fluorobenzoic acid; 3,5-difluorobenzoic acid; 3,4-difluorobenzoic acid; 2,6-difluorobenzoic acid; 2,5-difluorobenzoic acid; 2,3-difluorobenzoic acid; 2,4-difluorobenzoic acid; pentafluorobenzoic acid; 2,3,4,5-tetrafluorobenzoic acid; 4-(trifluoro-methyl)benzoic acid; 2-(trifluoromethyl)benzoic acid; 3-(trifluoro-methyl)benzoic acid; 3,4,5-trifluorobenzoic acid; 2,4,5-trifluorobenzoic acid; 2,3,4-trifluorobenzoic acid; 2,3,5-trifluorobenzoic acid; 2,3,6-trifluorobenzoic acid; 2,4,6-trifluorobenzoic acid; and the like, perfluoromethylcyclopentane (PMCP), perfluoromethylcyclohexane (PMCH), perfluorodimethylcyclobutane (PDMCB), m-perfluorodimethylcyclohexane (m-PDMCH), o-perfluorodimethylcyclohexane (o-PDMCH), p-Perfluorodimethylcyclohexane (p-PDMCH), perfluorotrimethylcyclohexane (PTMCH), perfluoroethylcyclohexane (PECH), perfluoroisopropylcyclohexane (IPPCH), and the like.
Any chemical compound can be used as tracer with the present invention if it is not present at a measurable level in the reservoir fluids being produced from the well being tested, it can be measured at levels sufficiently low to allow its use to be economical, and the tracer does not interfere or interact undesirably with other materials present in the oil well at the levels used. Preferably, the tracers are detectable at a range of from about 1 parts per trillion to about 10,000 parts per million in the fluid being analyzed. Preferably the tracers are detectable at a range of from 5 parts per trillion to about 1,000 parts per million. More preferably the tracers are detectable at a range of from 100 parts per trillion to about 100 parts per million. At concentrations greater than about 1000 parts per million, the use of some tracers can become prohibitively expensive or cause unacceptable interactions with other materials present in an oil well.
The tracers of the present invention are desirably compatible with the fluids wherein they are used. Preferably, the tracer selected is chosen to be more compatible with the injected materials than with the reservoir fluids which may recovered concurrently with the injected materials. The fluorinated benzoic acids are particularly preferred as tracers for the present invention because they are compatible in both aqueous fluids as a salt and in organic based fluids as an acid.
In an alternative embodiment of the present invention, more than one tracer can be used to measure multiple operations in the same well. For example, oil wells often have more than one producing strata or zone. In the practice of the present invention, a fracture job could be done on one strata using a first tracer and a fracture job could be done on another strata using a second tracer. In recent years, horizontal drilling has allowed for the drilling of multiple bores terminating in a common bore which connects to the surface. In multilateral wells such as these, several different tracers could be used to keep track of concurrent recovery of materials from the several legs (lateral bores) of such wells.
In a similar but different embodiment, the method of the present invention is used in a process to fracture stimulate multiple intervals in single or multiple formations, within the same wellbore. This is performed by: (i) perforating a first interval; (ii) stimulating that first interval; (iii) isolating the first interval, (iv) perforating a second interval; (v) stimulating the second interval; (iii) isolating the second interval; and continuing this pattern. There may be as many as 12 or 13 such stimulations done on a single wellbore in a short period of time, sometimes only weeks or even days. The operator of the well will then retrieves the isolation mechanism, typically a bridge plug, between each interval and begins to clean up all of the stimulated intervals, often at one time. The method of the present invention is very useful in such an operation because a different tracer can be used in each interval and thus can be individually detected during the flowback. The method of the present invention thereby provides an opportunity for a well operator to determine which to what extent each of the intervals is contributing to the flowback.
In the practice of the present invention, a tracer is admixed with a material that is to be injected into an oil well. The tracer can be premixed with the injection material or it can be admixed as it is injected. Preferably the tracer is admixed with the injection material through a static mixer as the admixture is pumped into the oil well. Any method known to those of ordinary skill in the art of admixing and injecting materials into oil wells can be used with the method of the present invention.
In one preferred embodiment, where a stream of fluids used for a hydraulic fracture job is being pumped into an oil well, a ten percent solution of a fluorinated benzoic acid salt tracer is pumped into the stream of fluids being used for a hydraulic fracture job, just upstream of a static mixer, using a peristaltic pump to meter the tracer into the stream of fluids. In another preferred embodiment, the pump used to feed the tracer solution into the fracture fluids is a triplex or a centrifugal pump. In either embodiment, the metering pump is adjusted such that the tracer is injected into the fracture fluids at a rate that results in a predetermined tracer concentration appropriate for the conditions in the oil well. The same process can also be used for injecting tracer into a stream of drilling fluids.
In the practice of the present invention, the chemical tracer compound is admixed with a material to be injected into an oil well at a predetermined concentration. The concentration of the tracer is above its detection limits and preferably at a concentration of ten times its detection limits. In the practice of the present invention, preferably the concentrations of the tracer and the total amount of admixture injected is determined and known.
After the fluid injected into an oil well during the practice of the present invention has performed its purpose, it is preferably recovered. Most often, the injected materials are recovered along with reservoir fluids as a production fluid. In the practice of hydraulic fracturing of wells, this phase of the process is the fracture clean up. In conventional practices, this process can take an extended amount of time where up to 72 hours would not be unusual.
In the practice of the present invention, the recovered materials are tested for tracer concentration and the amount of material recovered determined. At this point, the well operator can make an informed decision regarding whether to continue clean up or begin production.
The extent of recovery of materials injected including a tracer of the present invention is preferably determined by using a mass balance approach. Therein, the total amount of tracer admixed with the injected material is a known. A homogenous sample of production fluid is tested for tracer concentration and the amount of tracer recovered is thereby determined. The amount of injected admixture recovered is then determined using the formula:
AMTr=((Tr/Ti)xc3x97AMTi)
wherein AMTr is the amount of injected admixture recovered, Ti is the amount of tracer injected; Tr is the amount of tracer recovered; and AMTi is the amount of materials injected. Tr is determined by multiplying the concentrations of the tracer in the production fluid by the total quantity of production fluid recovered.
Where a mass balance approach is not possible or desirable, a relative rate of recovery can also be determined by measuring the concentration of tracer in the production fluids recovered from an oil well as a function of time. In a process such as this, samples of production fluid being recovered from the well are taken, analyzed for tracer concentration that is then plotted against time and/or flow rates. This can also be a desirable way for an operator to decide when to begin production from an oil well.
The tracers used with the method of the present invention can be analyzed by any method known to those of ordinary skill in the art of doing such analyses to be useful. For example, in one method of analyzing for a fluorinated benzoic acid tracer of the present invention, an emulsion of hydrocarbons, water and naturally occurring inorganic materials is first acidified with dilute hydrochloric acid and then extracted using a nonpolar solvent. The organic phase is then admixed with a 1 normal sodium hydroxide solution and then extracted with water. The water is then reacidified and extracted with methylene chloride. The recovered methylene chloride is then analyzed for the tracer, optionally after being reduced in volume by evaporation.
In addition to methylene chloride, other solvents can be used. For example, cyclohexane, normal hexane, pentane, can be used. While not preferred, organic solvents such as benzene and toluene can also be used as long as care is used to make sure that the solvent does not have a significant background level of the tracer being used.
In the case of the fluorinated benzoic acid tracers, very low levels of tracer can be determined by taking advantage of the carboxylate group to first separate the tracer from non-acidic organics as a salt and then, in a second step, concentrate the tracer into an organic solvent by returning it to its acid form and then extracting it from an aqueous phase.
There are many instrumental methods of analyzing for the tracer compounds useful with the method of the present invention, including but not limited to, gas chromatography (GC) using flame ionization detectors, electron capture detectors, and the like; liquid chromatography (LC); infrared spectroscopy; combination instrumentation such as Fourier transform infrared spectroscopy, GC-mass spectroscopy, LC-mass spectroscopy, and the like.
When especially demanding analytical conditions arise, other means of doing the analyses can also be used, including using biologically active tracers for immunoassay, preparing functional derivatives of the tracers including, for example, esterifacation with more easily analyzed alcohols, and the like.
To achieve low levels of detection, it is necessary that standard laboratory practices be maintained. Fluids produced from oil wells can contain hazardous or toxic materials and steps should be taken to ensure the safety of lab personnel including, but not limited to, avoiding fire hazards, scrubbing or removing H2S and other harmful gasses, and limiting skin contact with possible carcinogens. Quality assurance should be done as with any analytical procedure including using internal standards, external standards, and the like to ensure the accuracy of analyses. Recovery efficiencies can vary from oil well to oil well. It is important not to overlook simple steps such as accurately measuring sample volumes and filtering irrelevant solids from samples prior to analysis. Any analytical method that can detect the chemical tracers useful with the method of the present invention at useful levels can be used with the present invention.
In another embodiment of the present invention, the tracer is in the form of a coating on a solid substrate. In this application, the tracer is released gradually into production fluid over time. When co-injected with solids such as proppant or pack sand, this use of the tracers of the present invention would allow for an estimation of the amount of co-injected solids in place in the well. If too little tracer were detected after completion of the injection, or if the tracer level decreased too quickly after completion, an oil well operator would know that the injected solids were either not properly placed in the well or are being washed out or otherwise being removed from the oil well.

Method for determining the extent of recovery of materials injected into oil wells during oil and gas exploration and production


This invention provides compounds of formula I having the structure

The present invention relates to cycloocta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives thereof, which are serotonin 5-hydroxytryptamine 2c (5HT2C) receptor agonists useful for the treatment of disorders, such as obsessive-compulsive disorder, depression, anxiety, generalized anxiety disorder, schizophrenia, migraine, sleep disorders, eating disorders, obesity, epilepsy, and spinal cord injury.
Obesity is a medical disorder characterized by an excess of body fat or adipose tissue. Comorbidities associated with obesity are Type II diabetes, cardiovascular disease, hypertension, hyperlipidemia, stroke, osteoarthritis, sleep apnea, gall bladder disease, gout, some cancers, some infertility, and early mortality. As the percentage of obese individuals continues to rise both in the U.S. and abroad, obesity is expected to be a major health risk in the 21st Century. The serotonin 5-hydroxytryptamine (5-HT) receptor is a G-protein coupled receptor which is expressed in neurons in many regions of the human central nervous system. [Wilkinson, L. O. and Dourish, C. T. in Serotonin Receptor Subtypes: Basic and Clinical Aspects (ed. Peroutka, S. J. ) 147-210 (Wiley-Liss, New York, 1991).] The 5HT2C receptor (formerly called the 5HT1C receptor) is a prominent subtype of the serotonin receptor found in the central nervous system of both rats and humans. It is expressed widely in both cortical and subcortical regions. [Julius, D. MacDermott, A. B., Axel, R. Jessell, T. M. Science 241:558-564 (1988).] Studies in several animal species and in humans have shown that the non-selective 5HT2C receptor agonist, meta-chlorophenylpiperazine (MCPP) decreases food intake. [Cowen, P. J., Clifford, E. M. , Williams, C., Walsh, A. E. S., Fairburn, C. G. Nature 376: 557 (1995).] Tecott, et al have demonstrated that transgenic mice lacking the 5HT2C receptor eat more and are heavier than Wild Type mice. [Tecott, L. H., Sun, L. M., Akana, S. F., Strack, A. M., Lowenstein, D. H., Dallman, M. F., Julius, D. Nature 374:542-546 (1995).] Compounds of this invention are 5HT2C receptor subtype selective agonists which are selective over other monoamine receptors, causes a reduction in food intake and result in a reduction in weight gain. Other therapeutic indications for 5HT2C agonists are obsessive compulsive disorder, depression, panic disorder, schizophrenia, sleep disorders, eating disorders, epilepsy, and spinal cord injury.
U.S. Pat. No. 3,914,250 (Oct. 21, 1975) describes 1,4-diazepino[6,5,4-jk]carbazoles as anticonvulsant agents. The compounds of this invention are not carbazoles. This invention relates to cycloocta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives which bind to and activate 5HT2C receptors in the CNS and are useful for the treatment of CNS disorders which can benefit from modulation of the 5HT2C receptor.
This invention provides compounds of formula I having the structure
wherein:
R1 and R2 are each independently selected from hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, fluorinated alkyl of 1-6 carbon atoms, xe2x80x94CN, xe2x80x94NHxe2x80x94SO2-alkyl of 1-6 carbon atoms, xe2x80x94SO2xe2x80x94NH-alkyl of 1-6 carbon atoms, alkyl amide of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, fluorinated alkoxy of 1-6 carbon atoms, acyl of 2-7 carbon atoms, or aroyl;
R3, R4 are each independently hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl or xe2x80x94CH2xe2x80x94C3-C7 cycloalkyl;
R5 is hydrogen or C1-C6 alkyl;
R6 is hydrogen or C1-C6 alkyl; and
wherein the dashed line indicates an optional double bond; or a pharmaceutically acceptable salt thereof.
In the definitions of R1 and R2 herein, the fluorinated alkyl and fluorinated alkoxy groups indicate the specified alkyl or alkoxy groups having any amount of fluorine substitution including, but not limited to, groups such as xe2x80x94CHF2, xe2x80x94CF3, xe2x80x94C2F5, xe2x80x94OCF3, etc.
The dashed line in formula I indicates an optional double bond, indicating the optional reduction described above.
One group of compounds of this invention comprises those of the formulae:
wherein
R1 and R2 are each independently selected from hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, trifluoromethyl, xe2x80x94CN, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, or trifluoromethoxy;
R3, R4 are each independently hydrogen or C1-C6 alkyl;
R5 is hydrogen or C1-C6 alkyl;
R6 is hydrogen or C1-C6 alkyl; or a pharmaceutically acceptable salt thereof.
Another group of compounds of this invention comprises those in which each of R1, R2, R3, R4, R5, and R6 are independently selected from H or alkyl of 1-6 carbon atoms, or a pharmaceutically acceptable salt thereof.
The 5HT2C receptor agonists of this invention are useful for the treatment or prevention in mammals, preferably in humans, of disorders involving the central nervous system such as obsessive-compulsive disorder, depression, atypical depression, bipolar disorders, anxiety, generalized anxiety disorder, schizophrenia, psychoses, personality disorders, organic mental disorders, behavioral disorders associated with dementia or age-related conditions, aggressivity, drug and alcohol addiction, social phobias, sexual dysfunction, panic disorder, migraine, sleep disorders, such as sleep apnea, eating disorders, such as hyperphagia, bulimia or anorexia nervosa, obesity, epilepsy, and premenstrual tension.
This invention also includes methods of utilizing the compounds herein in treatments or preventative regimens for treatment of central nervous system deficiencies associated with trauma, stroke, neurodegenerative diseases or toxic or infective CNS disorders including, but not limited to, encephalitis or meningitis; or cardiovascular disorders, including thrombosis; gastrointestinal disorders such as malfunction of gastrointestinal motility; and diabetes insipidus. These methods include the improvement or inhibition of further degradation of central nervous system activity during or following the malady or trauma in question. Included in these improvements are maintenance or improvement in motor and motility skills, control, coordination and strength.
These methods of this invention comprise administering to a mammal in need thereof a pharmaceutically or therapeutically effective amount of a compound of this invention, or a pharmaceutically acceptable salt thereof.
The compounds of this invention contain asymmetric carbon atoms and thus give rise to optical isomers and diastereoisomers. While shown without respect to stereochemistry in Formula I, the present invention includes such optical isomers and diastereoisomers; as well as the racemic and resolved, enantiomerically pure R and S stereoisomers; as well as other mixtures of the R and S stereoisomers and pharmaceutically acceptable salts thereof.
The term xe2x80x9calkylxe2x80x9d includes both straight- and branched-chain saturated aliphatic hydrocarbon groups and cycloalkyl groups. Halogen is defined as Cl, Br, F, and I. The term xe2x80x9caroylxe2x80x9d is defined as an aryl ketone, where aryl is defined as an aromatic system of 6-14 carbon atoms, which may be a single ring or multiple aromatic rings fused or linked together as such that at least one part of the fused or linked rings forms the conjugated aromatic system. Preferred aryl groups include phenyl, thiophenyl, naphthyl, biphenyl, anthryl, tetrahydronaphthyl, phenanthryl groups.
Pharmaceutically acceptable salts can be formed from organic and inorganic acids, for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, napthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable acids.
Preferred compounds of this invention are those in which R is hydrogen. Especially preferred are compounds which are enantiomerically pure stereoisomers of compounds where R is hydrogen and the indole ring is reduced or not reduced.
The compounds of this invention can be prepared according to the following scheme from commercially available starting materials or starting materials which can be prepared using literature procedures. Scheme 1 shows the preparation of a key intermediate and Scheme 2 shows the preparation of representative compounds of this invention.
According to Scheme 1, a substituted or unsubstituted isatoic anhydride is allowed to react with substituted or unsubstituted glycine hydrochloride or an ester of the same in an organic base such as pyridine or triethylamine, to give either open-chain intermediate I or the benzodiazepinedione II. Intermediate I can be converted to intermediate II by heating in the presence of an acid, such as acetic acid. The benzodiazepinedione II is reduced to the benzodiazepine III using a reducing agent such as lithium aluminum hydride or a borane-tetrahydrofuran complex. The secondary nitrogen atom in III is protected using a protecting group, such as an amide by reacting III with an acylating agent, such as acetic anhydride, in the presence of a base, such as triethylamine, to give an acylated benzodiazepine IV.
According to Scheme 2, Intermediate IV is allowed to react with a nitrosating agent, such as sodium nitrite, in the presence of an acid, such as acetic acid, to give nitroso compounds V. The nitroso compounds are reduced to hydrazines VI using a reducing agent, such as zinc powder in acetic acid and water. The hydrazines VI are allowed to react with substituted or unsubstituted cyclooctanones in acid, such as acetic acid, to give the fused indoles VII. The fused indoles VII can be treated with a base, such as NaOH, in a polar solvent, such as water or an alcohol, or with an acid, such as hydrochloric acid, to give the fused indoles VIII, which are products of this invention. In addition, fused indoles VIII can be reduced, with a reducing agent, such borane in THF, in the presence of an acid, such as trifluoroacetic acid, to give fused indolines IX which are products of this invention. Fused indolines IX are diastereoisomeric mixtures that can be resolved using chiral HPLC or chiral resolving agents to give stereo isomers X and XI and enantiomers thereof, which are products of this invention. Also, compounds VII can be reduced with reducing agents, such as a borane-THF complex, to give XII which are compounds of this invention.
The acylation steps of this invention are understood to include reactions of the appropriate compound with any acylating agent and reaction conditions known in the art. Useful in these steps are acylating agents include acid halides and esters or anhyrides of the appropriate aliphatic carboxylic acid. Useful acid halides include acetyl chloride, propionyl chloride, isobutyryl chloride, benzoyl chloride, etc. Acid anhydrides include acetic anhydride and benzoic anhydride. Similarly, alkylation steps herein are understood to include any relevant alkylating agents and conditions known in the art. These include, but are not limited to the use of alkyl halides, such as methyl iodide, or alkyl tosylates or aldehyde alkylating agents in the presence of an applicable reducing agent.
Pharmaceutically acceptable salts can be formed from organic and inorganic acids, for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, napthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known pharmaceutically acceptable acids. The processes herein will be understood to include an optional additional step of forming a salt form of the products via standard addition reactions with any pharmaceutically acceptable organic or inorganic acid.
The ability of the compounds of this invention to act as 5HT2C agonists was established in several standard pharmacological test procedures; the procedures used and results obtained are provided below.
Test Procedures
5HT2C Receptor Binding Test Procedure
To evaluate high affinity for the 5HT2C receptor, a CHO (Chinese Hamster Ovary) cell line transfected with the cDNA expressing the human 5-hydroxytryptamine2C (h5HT2C) receptor was maintained in DMEM (Dulbecco""s Modified Eagle Media) supplied with fetal calf serum, glutamine, and the markers: guaninephosphoribosyl transferase (GTP) and hypoxanthinethymidine (HT). The cells were allowed to grow to confluence in large culture dishes with intermediate changes of media and splitting. Upon reaching confluence, the cells were harvested by scraping. The harvested cells were suspended in half volume of fresh physiological phosphate buffered saline (PBS) solution and centrifuged at low speed (900xc3x97g). This operation was repeated once more. The collected cells were then homogenized with a polytron at setting #7 for 15 sec in ten volumes of 50 mM Tris.HCl, pH 7.4 and 0.5 mM EDTA. The homogenate was centrifuged at 900xc3x97g for 15 min to remove nuclear particles and other cell debris. The pellet was discarded and the supernatant fluid recentrifuged at 40,000xc3x97g for 30 min. The resulting pellet was resuspended in a small volume of Tris.HCl buffer and the tissue protein content was determined in aliquots of 10-25 microliter (xcexcl) volumes. Bovine Serum Albumin (BSA) was used as the standard in the protein determination by the method of Lowry et al., (J. Biol. Chem., 193:265 (1951). The volume of the suspended cell membranes was adjusted with 50 mM Tris.HCl buffer containing: 0.1% ascorbic acid, 10 mM pargyline and 4 mM CaCl2 to give a tissue protein concentration of 1-2 mg per ml of suspension. The preparation membrane suspension (many times concentrated) was aliquoted in 1 ml volumes and stored at xe2x88x9270 C. until used in subsequent binding experiments.
Binding measurements were performed in a 96 well microtiter plate format, in a total volume of 200 xcexcl. To each well was added: 60 xcexcl of incubation buffer made in 50 mM Tris.HCl buffer, pH 7.4 and containing 4 mM CaCl2; 20 xcexcl of [125I] DOI (S.A., 2200 Ci/mmol, NEN Life Science).
The dissociation constant, KD of [125I] DOI at the human serotonin 5HT2C receptor was 0.4 nM by saturation binding with increasing concentrations of [125I] DOI. The reaction was initiated by the final addition of 100.0 xcexcl of tissue suspension containing 50 xcexcg of receptor protein. Nonspecific binding is measured in the presence of 1 xcexcM unlabeled DOI added in 20.0 xcexcl volume. Test compounds were added in 20.0 ml. The mixture was incubated at room temperature for 60 min. The incubation was stopped by rapid filtration. The bound ligand-receptor complex was filtered off on a 96 well unifilter with a Packard(copyright) Filtermate 196 Harvester. The bound complex caught on the filter disk was dried in a vacuum oven heated to 60xc2x0 C. and the radioactivity measured by liquid scintillation with 40 xcexcl Microscint-20 scintillant in a Packard TopCount(copyright) equipped with six (6) photomultiplier detectors.
Specific binding is defined as the total radioactivity bound less the amount bound in the presence of 1 xcexcM unlabeled DOI. Binding in the presence of varying concentrations of test drugs is expressed as percent of specific binding in the absence of drug. These results are then plotted as log % bound vs log concentration of test drug. Non linear regression analysis of data points yields both the IC50 and the Ki values of test compounds with 95% confidence limits. Alternatively, a linear regression line of decline of data points is plotted, from which the IC50 value can be read off the curve and the Ki value determined by solving the following equation:   Ki  =      IC50          1      +              L        /        KD
where L is the concentration of the radioactive ligand used and the KD is the dissociation constant of the ligand for the receptor, both expressed in nM.
The following Ki""s are provided for various reference compounds:
Ki value and 95% confidence interval.
Ritanserin 2.0 (1.3-3.1) nM
Ketanserin 94.8 (70.7-127.0) nM
Mianserin 2.7 (1.9-3.8) nM
Clozapine 23.2 (16.0-34.0) nM
Methiothepin 4.6 (4.0-6.0) nM
Methysergide 6.3 (4.6-8.6) nM
Loxapine 33.0 (24.0-47.0) nM
mCPP 6.5 (4.8-9.0) nM
DOI 6.2 (4.9-8.0) nM
Stimulation of [3H] Inositol Monophosphate Production by 5HT2C Agonists.
CHO cells transfected with the cDNA expressing the human 5-HT2C receptor were cultured in Dulbecco""s modified Eagle""s medium (DMEM) supplemented with 10% fetal bovine serum and non-essential amino acids. Upon reaching confluence the cells were harvested using PBS/EDTA and plated in 24 well plates at an initial density of 2.5xc3x97105 cells per well. One (1) ml of maintenance medium containing 1 xcexcCi/ml myo-[3H] inositol was added to each well. After 48 hours labeling, the cells were washed once with 0.5 ml DMEM containing 25 mM HEPES and 10 mM LiCl, then preincubated with the medium for 30 min (antagonists were included in this period if tested). At the end of the preincubation, the medium was removed, the cells were then incubated with test compounds (in presence of antagonists if needed) for 30 min. The reaction was terminated by removal of the incubation solution and addition of 0.5 ml ice-cold 5% PCA, followed by 15 to 30 min incubation on ice. 200 xcexcl of 0.5 M Tes/1.5 M K2CO3 was added to each well to neutralize to pH 7, and plates were left on ice for another 15 to 30 min to precipitate all salts. The liquid and solid phases were separated by centrifugation.
A portion (350 xcexcl) of the upper aqueous phase was applied to Dowex AG-1X8 (formate form, 100-200 mesh) columns. The columns were then washed stepwise with 10 ml of water and 10 ml of 25 mM ammonium formate to remove free myo-[3H]inositol and deacylated phosphoinositol, respectively. Finally 10 ml of 0.2 M ammonium formate solution was applied to the columns to elute [3H] inositol monophosphate ([3H] IP1) directly into scintillation vials. Of this eluate, 1 ml was used to determine radioactivity by scintillation counting.
Agonist-stimulated levels of [3H]inositol monophosphate (IP1) is expressed as a percentage of the response observed with a maximally effective concentration of 5-HT (10 xcexcM). A 3-parameter logistic function is used to generate estimate of EC50/IC50. Antagonists are tested in the presence of 10 xcexcM 5-HT.
The following data are provided for various reference compounds:
Results
The results obtained in this standard pharmacological test procedures demonstrate that the compounds of this invention are 5HT2C receptor agonists useful for the treatment of diseases involving the central nervous system such as obsessive-compulsive disorder; depression; anxiety; generalized anxiety disorder, panic disorder; schizophrenia; migraine; sleep disorders, such as sleep apnea; eating disorders, such as hyperphagia; obesity; epilepsy, and spinal cord injury.
This invention also comprises pharmaceutical compositions comprising a pharmaceutically or therapeutically effective amount of one or more compounds of this invention, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutical carriers or excipients. The compounds of this invention can be formulated neat or with a pharmaceutical carrier for administration, the proportion of which is determined by the solubility and chemical nature of the compound, chosen route of administration and standard pharmacological practice. The pharmaceutical carrier may be solid or liquid.
A solid carrier can include one or more substances which may also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders or tablet-disintegrating agents; it can also be an encapsulating material. In powders, the carrier is a finely divided solid which is in admixture with the finely divided active ingredient. In tablets, the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain up to 99% of the active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins.
Liquid carriers are used in preparing solutions, suspensions, emulsions, syrups, elixirs and pressurized compositions. The active ingredient can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fats. The liquid carrier can contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators. Suitable examples of liquid carriers for oral and parenteral administration include water (partially containing additives as above, e.g. cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, e.g. glycols) and their derivatives, lethicins, and oils (e.g. fractionated coconut oil and arachis oil). For parenteral administration, the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid carriers are useful in sterile liquid form compositions for parenteral administration. The liquid carrier for pressurized compositions can be halogenated hydrocarbon or other pharmaceutically acceptable propellant.
Liquid pharmaceutical compositions which are sterile solutions or suspensions can be utilized by, for example, intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be administered intravenously. The compounds of this invention can also be administered orally either in liquid or solid composition form.
The compounds of this invention may be administered rectally or vaginally in the form of a conventional suppository. For administration by intranasal or intrabronchial inhalation or insufflation, the compounds of this invention may be formulated into an aqueous or partially aqueous solution, which can then be utilized in the form of an aerosol. The compounds of this invention may also be administered transdermally through the use of a transdermal patch containing the active compound and a carrier that is inert to the active compound, is non toxic to the skin, and allows delivery of the agent for systemic absorption into the blood stream via the skin. The carrier may take any number of forms such as creams and ointments, pastes, gels, and occlusive devices. The creams and ointments may be viscous liquid or semisolid emulsions of either the oil-in-water or water-in-oil type. Pastes comprised of absorptive powders dispersed in petroleum or hydrophilic petroleum containing the active ingredient may also be suitable. A variety of occlusive devices may be used to release the active ingredient into the blood stream such as a semipermeable membrane covering a reservoir containing the active ingredient with or without a carrier, or a matrix containing the active ingredient. Other occlusive devices are known in the literature.
As used herein, the terms xe2x80x9cpharmaceutically effective amountxe2x80x9d or xe2x80x9ctherapeutically effective amountxe2x80x9d means the total amount of each active component of the pharmaceutical composition or method that is sufficient to show a meaningful patient benefit, i.e., treatment, prevention or amelioration of the cause or symptoms of the malady or condition, or an increase in rate of treatment, prevention or amelioration of such conditions. When applied to an individual active ingredient, administered alone, the term refers to that ingredient alone. When applied to a combination, the term refers to combined amounts of the active ingredients that result in the therapeutic effect, whether administered in combination, serially or simultaneously.
The dosage requirements vary with the particular compositions employed, the route of administration, the severity of the symptoms presented and the particular subject being treated. Daily dosages of active compound would be 0.02 xcexcg/kg-750 xcexcg/kg. Treatment will generally be initiated with small dosages less than the optimum dose of the compound. Thereafter the dosage is increased until the optimum effect under the circumstances is reached; precise dosages for oral, parenteral, nasal, or intrabronchial administration will be determined by the administering physician based on experience with the individual subject treated. Preferably, the pharmaceutical composition is in unit dosage form, e.g. as tablets or capsules. In such form, the composition is sub-divided in unit dose containing appropriate quantities of the active ingredient; the unit dosage forms can be packaged compositions, for example, packaged powders, vials, ampoules, pre filled syringes or sachets containing liquids. The unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form.

Abstract: wherein: R1 and R2 are H, alkyl, cycloalkyl, alkoxy, halogen, fluorinated alkyl, xe2x80x94CN, xe2x80x94NHxe2x80x94SO2-alkyl, xe2x80x94SO2xe2x80x94NH-alkyl, alkyl amide, amino, alkylamino, dialkylamino, fluorinated, acyl, or aroyl; R3, R4 are H, alkyl, cycloalkyl or xe2x80x94CH2-cycloalkyl; R5 is H or alkyl; R6 is H or alkyl; and wherein the dashed line indicates an optional double bond; or a pharmaceutically acceptable salt thereof, as well as methods for using these compounds to treat central nervous system disorders, including obsessive-compulsive disorder, depression, anxiety, generalized anxiety disorder, schizophrenia, migraine, sleep disorders, eating disorders, obesity, epilepsy, and spinal cord injury.