Pharmaceutical compositions for treating bone lesions in multiple myeloma or pharmaceutical compositions for treating multiple myeloma which contain as an active ingredient a compound having both of an effect of suppressing bone resorption accompanying multiple myeloma and an effect of inhibiting multiple myeloma, more particularly, 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane-1,1-bisphosphonic acid or its salt.

This invention relates to medicines, in particular, pharmaceutical compositions for treating bone lesions in multiple myeloma and pharmaceutical compositions for treating multiple myeloma.
Multiple myeloma is a neoplastic disease in plasma cells which produce and secrete immunoglobulins (Ig""s). The Ig""s thus produced are homogeneous proteins called M proteins. The M proteins are observed in the blood in most cases. Known examples of these M proteins include IgG, IgA, BJP, IgD, IgE and IgM. BJP is a protein comprising the L chain of Ig (Bence Jones Protein: BJP) alone. The main focus of this disease resides in bone marrow. Myeloma cells tubercularly proliferate in the bone marrow and thus bone lesions frequently arise. In addition, clinical pictures such as anemia, renal failure and immunodeficiency are observed.
Among all, osteolytic bone lesions are pathognomonic symptoms which are observed in most patients with multiple myeloma. It has been clarified that these bone lesions also affect the prognosis of patients with multiple myeloma and relate to the survival time. Further, bone pain due to bone lesions and pathologic fracture and neuropathy due to spinal compression fracture are causative factors worsening patients"" quality of life (QOL). It is known that these bone lesions pathologically include clinical pictures of osteolysis, osteoporosis, bone fracture and combinations thereof. Studies are now under way on the onset mechanism of bone lesions in patients with multiple myeloma. At the present time, it is proposed that parathyroid hormone-related protein (PTHrP), which is a cytokine secreted from myeloma cells and has effects of promoting the formation of osetoclasts and enhancing the activity thereof, might participate therein (Byori to Rinsho, 17(1), 12-17, 1999).
In treating multiple myeloma, use is mainly made of chemotherapies (MP therapy, VAD therapy, C-VAD therapy, polypharmacy, etc.) and chemotherapy with the use of IFN-xcex1. Also, topical radiotherapy and the like are selected depending on the bone lesion conditions (Clinical Oncology, edited by Japan Clinical Oncology Group, published in 1996 by Gan to Kagakuryoho Sha). As the results of the long-term observation on patients with multiple myeloma under chemotherapy, it is reported that a bone resorption marker in urine did not correlate to changes in M proteins due to chemotherapy in many cases, though a tendency toward a decrease in the bone resorption marker was observed in a chemotherapy reaction group showing a decrease of 25% or more in M proteins (Blood, 90, 3743-3750, 1997). Therefore, it becomes more and more necessary to establish a novel therapy for bone lesions accompanying multiple myeloma from the viewpoint of patients"" QOL.
As medicines for inhibiting the progress of bone lesions (osteolysis and pathologic fracture) in multiple myeloma, bisphosphonate compounds (hereinafter referred to simply as BP) such as etidronate (7.5 mg/kg body weight, injection), clodronate (800 to 2,400 mg/day, oral, 300 mg/day, injection) and pamidronate (90 mg/4 weeks, intravenous drip) have been marketed in Europe and America. Although it is reported that risedronate (30 mg/day, oral), which is one of BPs, suppressed bone resorption and elevated bone mineral density in patients with multiple myeloma (Bone, Vol. 15, No. 1, p. 41-49, 1994), it has not yet approved as a medicine for treating multiple myeloma so far.
In case of using BPs as remedies for bone lesions in multiple myeloma, these compounds are administered in a higher dose than in case of using as remedies for osteoporosis. In addition, BPs are poor in oral absorbability, which considerably elevates the dose of oral BP preparations. The administration of BP in a high dose sometimes worsens the side effects typified by gastrointestinal disorders such as retching, diarrhea and abdominal pain, allergic reaction, hypocalcemia, mental disorders such as insomnia, etc. Therefore, BP preparations are administered to patients parenterally in many cases in practice as parenteral preparations such as injections or intravenous drips. Even clodronate, which is only one BP marketed as oral preparations, should be administered in a very high dose (800 to 2,400 mg/day) and thus burdens a large load to patients. However, BP should be continuously administered to sustain its effects. Therefore, it has been urgently required from the viewpoint of patients"" QOL to develop a low-dose oral medicine showing little side effects.
Recently, studies have been made on the anticancer effects of BP""s and it is reported that several BP""s have an effect of inhibiting cell proliferation in vitro (Britishi J. Haematology, 98, 665-672, 1997), though any clinical usefulness has been proved in none of these cases and some reports rather denying the anticancer effect of BPs are also presented. That is to say, it is reported that pamidronate has been used in a murine model of myeloma, and although no effect on tumor growth was demonstrated, there was evidence of a cytotoxic effect within the bone marrow. It is also reported that risedronate has been used in a murine model of myeloma; however, although there was a clear reduction in bone destruction, no effect on tumor burden was noted (Leukemia and Lymphoma, 32, 129-138, 1998). In a patient who was intravenously administered in a higher dose than in prior clinical studies, a transient decrease in a cancer marker was observed. However, it is reported that it is possible that for a cytostatic or even cytotoxic effect to occur, higher dose or more frequent administration of pamidronate is require compared to dosing for its beneficial bone effects (Britishi J. Haematology, 103, 530-532, 1998). Accordingly, it has never been reported hitherto that BPs exert an anticancer effect (i.e., a therapeutic effect on multiple myeloma) in patients with multiple myeloma.
As discussed above, it has been considered that BPs have a therapeutic effect on bone lesions in multiple myeloma but no therapeutic effect on multiple myeloma per se.
On the other hand, it is stated in JP-B-6-99457 and EP 354806 that 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane-1,1-bisphosphonic acid (hereinafter referred to as the compound A) or its salt, which is a bisphosphonic acid compound having a fused heterocycle skeleton, suppresses bone resorption, for example, accelerated bone resorption accompanying Bechet""S disease, hypercalcemia, cancer metastasis into bone, osteoporosis, inflammatory joint diseases such as rheumatoid arthritis, etc. (The term xe2x80x9cJP-Bxe2x80x9d as used herein means an xe2x80x9cexamined Japanese patent publicationxe2x80x9d.) It is actually confirmed that the compound A exerts a favorable effect of inhibiting bone resorption in osteoporosis. However, no report has been presented so far concerning the therapeutic effect on multiple myeloma and the therapeutic effect on bone lesions in multiple myeloma.
In the course of a study on the pharmacological effects of the compound A, the inventors have unexpectedly found out that it has a therapeutic effect on multiple myeloma per se. That is to say, they have found out that the compound A is a BP of a completely novel type which has an effect of suppressing bone resorption accompanying multiple myeloma and an effect of inhibiting multiple myeloma per se and, therefore, is usable particularly in treating bone lesions in multiple myeloma and multiple myeloma, thereby completing the invention.
Accordingly, the invention relates to pharmaceutical compositions for treating bone lesions in multiple myeloma and pharmaceutical compositions for treating multiple myeloma which contain as the active ingredient a compound having an effect of suppressing bone resorption accompanying multiple myeloma and an effect of inhibiting multiple myeloma.
Now, the invention will be described in detail.
The term xe2x80x9ccompound having an effect of suppressing bone resorption accompanying multiple myeloma and an effect of inhibiting multiple myelomaxe2x80x9d as used in the invention means a compound which has been confirmed as having an effect of suppressing bone resorption accompanying multiple myeloma and an effect of inhibiting the progress of multiple myeloma per se in a clinically acceptable administration dose and administration frequency in human clinics. More particularly speaking, it means the compound A or its salt which has been confirmed as having both of these effects at a low dose in clinical tests as will be described in Examples hereinafter. As the pharmaceutical compositions according to the invention, pharmaceutical compositions of the compound A or its salt for oral administration are preferable and pharmaceutical compositions of the compound A or its salt for oral administration to be used in a dose of 3 to 10 mg per day are still preferable.
The term xe2x80x9ctreating bone lesions in multiple myelomaxe2x80x9d as used in the invention means inhibiting or ameliorating bone lesions accelerated by multiple myeloma, for example, bone pain, osteolysis, bone fracture, skeletal fracture and/or decrease in bone mineral density. Further, amelioration of bone-related symptoms of patients with multiple myeloma accompanying the inhibition or amelioration of these bone lesions also falls within the scope of xe2x80x9ctreating bone lesions in multiple myelomaxe2x80x9d. The amelioration of bone-related symptoms of patients with multiple myeloma is exemplified by a decrease in the radiotherapy frequency, a decrease in the dose of analgesics used and a decrease in the frequency of performing surgical operations. Moreover, improvement in the QOL of patients with multiple myeloma accompanying the inhibition or amelioration of these bone lesions also falls within the scope of xe2x80x9ctreating bone lesions in multiple myelomaxe2x80x9d. For example, citation may be made of the improvement in the items reported as the result of a questionnaire on the QOL carried out by EORTC (European Organization for Research and Treatment of Cancer) (more particularly, physical activity, role activity, mental activity, social activity, general activity, pain, fatigue, nausea/retching, shortness of breath, insomnia, inappetence, constipation, diarrhea, economic conditions, etc.).
The term xe2x80x9ctreating multiple myelomaxe2x80x9d as used herein means inhibiting or ameliorating the progress of multiple myeloma via the inhibition of the proliferation of myeloma cells. In general, it can be confirmed depending on changes in immunoglobulin (Ig) which is a marker of the progress of myeloma. Moreover, a decrease in the administration frequency of chemotherapeutics and a decrease in the frequency of radiotherapy also fall within the scope of xe2x80x9ctreating multiple myelomaxe2x80x9d.
According to the prior reports, although tumor mass is reduced by chemotherapy but bone resorption does not correlate thereto in many cases (ibid., Blood). On the other hand, it is known that a bone resorption marker can be reduced by administering conventionally known BPs to patients with multiple myeloma but tumor mass is not affected thereby (ibid., Leukemia and Lymphoma).
In contrast thereto, it has been clinically confirmed for the first time that the pharmaceutical compositions containing the compound A according to the invention exert a therapeutic effect on multiple myeloma as medicinal BP compositions as well as an effect of inhibiting bone lesions accompanying multiple myeloma, as will be shown by Examples given hereinafter. Because of showing little side effects too, these pharmaceutical compositions are useful as medicinal BP compositions of a novel type satisfying the needs in practical medicine. In particular, it is expected that both of the effect of suppressing bone resorption and the effect of inhibiting myeloma of the compound according to the invention contribute to the treatment of bone lesions in multiple myeloma, thereby achieving more favorable results.
The pharmaceutical compositions according to the invention are applicable to the treatment of multiple myeloma or to the treatment of bone lesions in multiple myeloma. Needless to say, these compositions may be used for both of these purposes.
The pharmaceutical compositions according to the invention can be used together with other anticancer agents such as chemotherapeutics, if needed. While monitoring immunoglobulin (Ig) as a marker indicating the progress of myeloma to thereby confirm the progress of myeloma, the pharmaceutical compositions according to the invention can be administered optionally with the performance of an appropriate chemotherapy or radiotherapy. In case where the pharmaceutical compositions according to the invention are used to inhibit or ameliorate myeloma, it is expected that the administration frequency of these chemotherapeutics, etc. can be lowered. It is also expected that a more favorable effect of inhibiting myeloma can be established by the combined use of the pharmaceutical compositions according to the invention with other anticancer agents.
The 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane-1,1-bisphosphonic acid (compound A) or its salt according to the invention is described in JP-B-6-99457 and can be easily obtained by the method described in this document. The term xe2x80x9csaltxe2x80x9d as used herein is not particularly restricted but involves any pharmacologically acceptable salts. Particular examples thereof include salts with inorganic bases containing metals such as sodium, potassium, magnesium, calcium and aluminum, salts with organic bases such as methylamine, ethylamine, ethanolamine, lysine and ornithine, and ammonium salts. Furthermore, the compound A or its salt may be in any form of various hydrates, solvates or polymorphisms. In case of using as a solid preparation for oral administration, in particular, it is preferable to use 1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethane-1,1-bisphosphonic acid monohydrate (hereinafter referred to simply as the compound A monohydrate) crystals.
The pharmaceutical compositions according to the invention can be prepared by a conventionally employed method with the use of one or more member selected from among the compound A and its salts, pharmaceutically acceptable carriers, more particularly, drug carriers, excipients and other additives commonly employed in pharmaceutical preparations. The administration may be carried out either by oral administration in the form of tablets, pills, capsules, granules, powders, liquids and the like, or by parenteral administration in the form of injections such as intravenous injections or intramuscular injections, suppositories, percutaneous preparations and the like.
The solid compositions for oral administration according to the invention is used in the form of tablets, powders, granules, etc. In these solid compositions, one or more active ingredients are blended with at least one inert diluent, for example, lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, corn starch, polyvinyl pyrrolidone, aluminum magnesium silicate. These compositions may further contain additives other than the inert diluents in accordance with the conventional methods, for example, lubricants such as magnesium stearate, disintegrating agents such as calcium cellulose glycolate, stabilizers such as lactose or solubilization assisting agents such as glutamic acid or aspartic acid. Tablets or pills may be coated, if necessary, with sugar coating or gastric or enteric films made from sucrose, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose phthalate, macrogol, titanium oxide, talc or the like.
The liquid compositions for oral administration involve pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs, etc. These compositions contain inert diluents commonly employed, for example, purified water and ethanol. In addition to the inert diluents, these compositions may further contain auxiliary agents such as humectants and suspending agents, sweeteners, flavors, aromatics and preservatives.
The injection compositions for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions and emulsions. The aqueous solutions and suspensions contain, for example, distilled water for injection and physiological saline. Examples of the non-aqueous solutions and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, polysorbate 80 and the like. These compositions may further contain auxiliary agents such as preservatives, humectants, emulsifiers, dispersants, stabilizers (for example, lactose), solubilization assisting agents (for example, glutamic acid, aspartic acid). These compositions are sterilized by, for example, filtering through a bacteriostatic filter, adding bactericides or irradiating. It is also possible to produce these compositions by preparing sterile solid compositions and then dissolving in sterile water or sterile solvents for injections before using.
In case of usual oral administration, the daily dose ranges from about 1 to 20 mg, preferably from about 3 to 10 mg and still preferably from about 6 to 9 mg. The daily dose is administered once a day or divided into 2 to 4 doses per day. The dose may be appropriately determined case by case taking the body weight, conditions, age, sex, etc. of the patient into consideration.
In case of intravenous administration, the single dose ranges from about 0.1 to 10 mg, preferably from about 0.1 to 5 mg and still preferably from about 0.5 to 2 mg. The composition can be intravenously dripped in this dose once in 2 to 6 weeks, preferably once in 3 to 5 weeks and still preferably once in 4 weeks over 10 to 60 minutes (preferably 30 minutes). The dose may be appropriately determined case by case taking the body weight, conditions, age, sex, etc. of the patient into consideration.
Next, the effects of the pharmaceutical compositions according to the invention will be illustrated by reference to the following Examples. However, it is to be understood that the invention is not limited thereto.

Medicinal compositions for treating osseous lesion in multiple myeloma


A cardio-thoracic compression harness that includes a pair of bands are placed around the body of the user so as to compress and hold in place the thorax, sternum, and ribs. The device is positioned so that the bands contact the user""s body above and below the breasts. This allows a female user to wear the device while wearing a bra. The device can also be constructed as a device integral to an undergarment such as a bra. The device includes a plurality of closures so that it can conform easily to the shape of the user""s body. The device may also include shoulder straps for more secure positioning. The harness can be worn under or over the user""s clothing.

This invention relates generally to medical support devices, and more particularly is a post-operative open heart and thoracic surgery elastic assisting device to reduce pain while allowing increased upper torso movement, particular that of the arms and shoulders, that reduces the transfer of energy and usage of chest wall musculature when performing upper arm and body tasks.
In 1996, according to the American Heart Association, there were 753,345 open heart procedures performed in the United States alone. That number does not include other sternotomy procedures. The essential access to the heart in performance of a cardiac procedure is obtained by cutting the patient at mid-chest from the collar bone to the solar plexus, (approximately 12 inches), and then opening the chest cage at that mid-point. The chest cage is opened by spreading the rib cage so that access to the heart and lungs is obtained. Closure of the chest cage is accomplished by placing the sternum in its original position and binding it with surgical wire, then suturing the approximately 12 inch skin opening. There is no casting of the area and the only means of ensuring closure of the sternum break to allow healing/regeneration is the surgical wire. Upper arm and torso movement, such as that required when opening doors, gripping rails on treadmills, tieing shoes, rolling during sleep, etc., causes substantial discomfort for which pain reducing drugs are prescribed.
The known prior art is relegated to the protection of the wearer from outside forces to the body such as described in xe2x80x9cShock Absorbing Athletic Equipmentxe2x80x9d, by Donzis, U.S. Pat. No. 4,513,449, issued Apr. 30, 1985. This device essentially contains padded air pockets to absorb the impact. Further known prior art is a xe2x80x9cRib Protectorxe2x80x9d, by Whiteside et al., U.S. Pat. No. 5,337,417, issued Aug. 16,1994. The device disclosed in this reference is also is an impact absorption device consisting of movable, substantially rigid plates in pockets which distribute the impact load. One additional prior art device that is somewhat related to the field of the present invention is the xe2x80x9cProtector and Article of Sportswear Using the Samexe2x80x9d, by Kato, et al., U.S. Pat. No. 5,337,418, issued Aug. 16, 1994. This device also is an impact device containing air cushions and rigid ribs.
A medical device used on the upper body of the patient is the xe2x80x9cAmbulatory Lumbo-Sacral Traction Systems and Methodsxe2x80x9d, by Scott, U.S. Pat. No. 4,715,362, issued Dec. 29, 1987. This device encircles a user under the arms and adjacent the pelvis. The device is used to apply traction and as a shock absorber, but discloses no means to provide a compression force on the user""s chest region. A medical device that does provide a means of compression is the xe2x80x9cPatient-Activated Body Immobilizer and Method of Usexe2x80x9d, by Williams, Jr., U.S. Pat. No. 4,641,642, issued Feb. 10, 1987. This device hangs loosely about the patient""s upper body, and is activated by the user applying pressure.
There are no prior art devices adapted to laterally and continually compress the chest wall in any manner, which isolates the pectoral muscles from pulling on the severed sections, thereby allow the post-operative or post-trauma patient to move more comfortably while healing. The current medical practice is to issue the patient a pillow to hold across his chest when trauma to the chest is imminent. Using this method, the patient loses the ability to use his arms. Further, this method cannot be used while the patient is sleeping (when coughing or sneezing can still occur). Medical journals have recognized the shortcomings of the xe2x80x9cpillow-to-the-chestxe2x80x9d method, and have explored methods to provide post-operative thoracic support, including internal fixation.
Accordingly, it is an object of the present invention to provide a device that continually compresses and holds in place the thorax and sternum post-surgery.
It is a further object of the present invention to provide a device that is adjustable by the user.
It is a further object of the present invention to provide a device that maintains pressure even when the patient is sleeping.
It is a still further object of the present invention to provide a device that is simple and inexpensive to manufacture.
The present invention is a cardio-thoracic compression harness that comprises at least one horizontal stretchable band applied to the thorax of the user. Preferably, a pair of bands are placed around the body of the user so as to compress and hold in place the sternum and thorax. The device is positioned so that the bands contact the user""s body above and below the breasts. This allows a female user to wear the device while wearing a bra. The device can also be constructed as a device integral to an undergarment such as a bra. The device includes a plurality of closures so that the device can conform easily to the shape of the user""s body without compressing breast tissue. Each band of the harness has an independent closure which permits adjustments, medical examination, and use of monitoring devices without releasing all the support of the harness. The harness may also include shoulder straps for more secure positioning. The device can be worn under or over the user""s clothing.
An advantage of the present invention is that it provides a means of adjustable compression, applicable by either the health-care provider or the patient, to the cardio-thoracic region of a post-trauma patient.
Another advantage of the present invention is that it can be worn either over or under the user""s clothing.
A still further advantage of the present invention is that it can be used in conjunction with a shoulder harness to hold the device more securely in place.
A further advantage of the present invention is that it provides a device that maintains pressure even when the patient is sleeping.
These and other objects and advantages of the present invention will become apparent to those skilled in the art in view of the description of the best presently known mode of carrying out the invention as described herein and as illustrated in the drawings.


Methods and systems for performing a surgical procedure using implantable sensors are disclosed. The method includes providing one or more implantable sensors, each sensor configured for implantation adjacent to an anatomical feature of a patient; imaging the patient to determine the relative positions of the one or more implantable sensors relative to the anatomical features of the patient; inserting an implant adjacent to at least one of the anatomical features; and tracking the position of the implant relative to the at least one anatomical feature during the inserting of the implant using the implantable sensors.

The present disclosure is directed to improved systems and methods for diagnosing, treating, and/or tracking medical conditions. More particularly, in some aspects the present disclosure is directed to systems and methods for diagnosing, treating, and/or tracking spinal disorders.
In addition to the areas that are scientific in nature, a significant portion of the practice of medicine is artistic in nature. The medical professional studies at length the biology, physiology and other disciplines related to his or her preferred medical specialty or practice, and thereafter may reference the scientific work of others for assistance. Further, he or she may have specific data obtained from measurements or assessments of the particular patient by way of x-rays, thermometers, electrocardiograms, and/or other devices and machines. Even though the data obtained may be undisputed, in many cases the root problem may not be entirely clear. Further, even where the root problem is clear there may be several possible treatment options. Accordingly, the physician or other medical professional will rely on experience, skill, and intuition to come to a conclusion as to what the most effective treatment may be for the patient.
While decisions based on experience, skill, and intuition are successful in many instances, in other instances these decisions result in a course of treatment that is less effective than had been hoped. In such cases, the patient may continue to be subjected to discomfort during the less-effective treatment, or a condition may worsen. Additionally, as medical procedures and devices become more expensive and time-consuming, it becomes more important to achieve a successful patient outcome in the first place from a resource-conservation standpoint as well. Accordingly, there is a need for improved devices, systems, and methods for diagnosing, treating, and/or tracking medical problems. For example and without limitation, there remains a need for improved devices, systems, and methods for diagnosing, treating, and/or tracking spinal disorders.

Methods and systems for diagnosing, treating, or tracking spinal disorders


A micromechanical pump has a membrane (2) positioned above a substrate (1). The substrate is provided with a cavity (8) which is formed in an endlessly continuous shape (e.g., circular) to provide a channel for a drive fluid. A cover (9) is positioned above the substrate with the membrane being between the substrate and cover. The cover is provided with an inlet (11) and outlet (10). Electrodes (3, 4) are provided around the floor of the cavity. The electrodes are selectively actuated so as to attract selected areas of the membrane resulting in a gap forming between the cover and the selected areas of the membrane. The areas of the membrane above the non-selected electrodes form a seal with the cover. By selectively actuating the electrodes a peristaltic pumping action results in a pumped fluid traveling from the inlet, through the gaps and out the outlet.

This application claims the priority of German Patent Document 199 22 612.1, filed May 17, 1999.
The invention relates to a micromechanical pump, with a peristaltic actuator for transporting and/or managing defined quantities of liquid or gas (pump medium).
The metering of minimum quantities of liquid in the microliter up to the nanoliter range is becoming ever more relevant for many applications in analytic chemistry and medical or environmental engineering. Frequently it is of interest to receive a defined quantity of liquid at one place, to transport it and deliver it at another place. Tasks of this nature are an essential part of quantitative analysis. Modern equipment can meter a few tens of microliters up to a few hundred microliters of a liquid with an accuracy of better than one percent by means of stepping motor-controlled injection pumps and precision pipettes. To manipulate, however, quantities of a few hundred nanoliters up to a few tens of microliters with the same accuracy, it is necessary to find other concepts of metering.
The micropump-based metering systems are dominated by two concepts. On the one hand, membrane pumps with two passive valves are used, and, on the other hand, valveless pumps, according to the diffuser nozzle principle, which are not sealed in the idle state, are used. Both types are unidirectional. That is, they can transport only in one direction. In both cases piezo actuators, which are cemented on the pump membrane, are usually used as the drive. An electrostatically driven micromembrane pump with passive valves is known from the German Patent DE 19719862. At high drive frequencies, this pump""s direction of delivery reverses itself owing to the inertia of the passive valves. However, this property can be used only to a limited degree for pumping backwards. The delivery rate is a function not only of the supplied power, but also of the properties of the pump medium to be pumped. Therefore, it is not possible to conclude from the supplied electric power the flow rate of an arbitrary pump medium. Since the volume displaced at each stroke of the pump is only a fraction of the volume of the pump chamber, the pump has a high dead volume.
The U.S. Pat. No. 57 05 018 discloses a micromechanical peristaltic pump, where the medium to be pumped is delivered by means of an electrically conductive membrane in a cavity equipped with electrodes. This pump has the drawback that it does not seal in the idle state and that the voltage between membrane and electrodes decreases across the medium to be pumped. Pumps with a circular drive element are disclosed, for example, in the WO 98/07199.
The principle of a pneumatic coupling of entrapped air volumes for a microvalve is known from the published German patent application DE 196 37 928 A1, where a micropump system, based on this principle, is disclosed. The drawback of this system is that the membrane does not form a tight seal at the cover. Hence, additional valves are needed to guarantee that the pump is tight in the idle state. Furthermore, since the delivery channel does not exhibit an endlessly continuous shape, the pump medium cannot be transported continuously without interruption. These drawbacks have a negative effect on the accuracy of the metering capability and on the output of the pump.
In summary one can state that there exist no metering systems that receive a predetermined quantity of liquid at one place and deliver it again at another place. Micropumps, which can meter precisely in the range below ten microliters, are also not available.
The invention is based on the problem of providing a bidirectional micropump, which can both transport in the microliter range continuously and manage defined volumes of liquid.
The micromechanical pump, based on the principle of a peristaltic actuator, is formed by stretching sealingly an electrically conductive membrane over a preferably ring-shaped hollow space, which continues endlessly in the linear direction and is filled with a drive medium, in a substrate (cavity). Electrodes, which can be driven separately at least to some degree, are installed permanently on the floor of the cavity. When some of the electrodes are driven, the membrane above the driven electrodes is pulled downwards; and through displacement of the drive medium the membrane above the non-driven electrodes is pressed upwards.
In this respect the electrodes have to be separated from the membrane with a passivating layer so that in the driven state no short circuit can occur between the electrodes and the membrane. This layer is applied preferably on the underside of the membrane and in the case of a silicon membrane is made preferably of a silicon oxide.
Because the cavity is closed, i.e. forms a hollow space with a fixed volume, and because this cavity contains the drive medium, the membrane must bulge upwards, owing to the displacement of the drive medium out of the areas of the cavity, in which the membrane is pulled downwards, to locations where the electrodes are not driven. If an adequate number of electrodes are driven, the drive medium is compressed below the upwardly bulging membrane areas in such a manner that the buckled areas are pressed firmly against the cover. This effect is called pneumatic coupling. While the electrodes are driven in pairs by a suitable method next to the buckled areas, the buckled areas can be slid over the cavity. The actuation of the electrodes is switched off in the pumping direction behind the buckling and switched on in front. Thus, it involves an indirect drive. The pump medium is displaced in the pumping direction not directly by the actuation of the electrodes, but by the displacement of one or several of the buckled area(s), under which the drive medium is compressed. The drive medium can be a liquid or a gas. If it is a liquid, then the volume of the liquid quantity must be less than the volume of the cavity. Owing to the incompressibility of liquids, the membrane cannot bulge downwards. Owing to the smaller volume of liquid, the membrane is bulged downwards already in the unactuated state. The results are analogous when, in the case of a gas as the drive medium, there is a vacuum in the hollow space of the cavity covered by the membrane.
It is especially advantageous, in the case of a vacuum of the drive medium or in the case of a liquid as the drive medium, if the membrane is under compressive stress, so that it forms a buckled area by itself (spontaneous buckling) without having to drive the electrodes. The spontaneous buckling can be achieved, for example, with a silicon membrane by oxidizing on a layer of silicon oxide. Such a membrane has the property that it bulges downwards and in other areas upwards in some areas over the cavity. The pump, according to the invention, holds its state, assumed last, by actuating the electrodes, even when the actuation of the electrodes is switched off. In the unpowered, i.e. non-driven state, the pump medium cannot flow through the pump in the case of spontaneous buckling of the membrane. In the ideal case the spontaneous buckling is characterized in conjunction with the vacuum or the fixed volume of liquid in the cavity in such a manner that the result is a desired number of seals, which are just adequately wide to cover the inlets and outlets of the pump.
To build a pump, the drive element, i.e. the membrane, is tightly covered with a flat cover, containing the inlet and the outlet. In the areas of the driven electrodes, where the membrane is pulled downwards, the result is a gap between the cover and the membrane, whereas in the areas of the, non-driven electrodes the membrane is pressed against the cover. This gap serves to receive the pump medium. When the electrodes are driven selectively, the area, in which the membrane is pressed against the cover, can be moved peristaltically from the inlet to the outlet. The pump medium, enclosed in the gap, is transported so as to be defined. However, the cover can also exhibit a notched surface above the cavity that is similar to the cavity, thus a passage. Due to the high forces pressing the membrane against the cover due to pneumatic coupling in the buckled membrane areas, the buckled area can adapt in accordance with the elasticity of the membrane to the shape of the passage.
Especially advantageous is the preferably annular shape of the cavity which forms an endlessly continuous channel for a drive medium such that the cross sectional shape of the cavity can match the shape of the downwards buckled membrane and the shape of the electrode is also curved in such a manner. In this case even if the membrane rests tightly against the substrate in the driven state and the drive medium can be displaced, therefore, only in the pumping direction, a continuous pumping process can be maintained. This would not be possible in the case of a cavity that were not endlessly continuous, since then the electrodes would have to be driven in such a manner that the drive medium for the next pump cycle would have to be displaced again in the direction of the inlet.
The cross sectional shape of the cavity that is adapted to the downwards buckled membrane is especially advantageous, if the drive medium is a gas, because then, as the electrodes are driven, the pressure increase in the gas, due to its lower volume, is especially high; and the membrane in the unselected areas is pressed tighter against the cover; and, therefore, the pump seals better. This feature is especially advantageous when used as a valve.
The pump is bidirectional. That is, there is the possibility of reversing at any time the pumping direction; and the pump has a low dead volume, a feature that is of decisive importance for pumps with compressible mediums, i.e., gases. The suction and the pump pressure of the pump, according to the invention, are approximately identical, since the shape of the bulges produced by the compressed gas or the fixed volume of the drive medium liquid is determined on all sides by means of the driven electrodes. The drive can occur separately from the medium. That is, the electrodes do not make contact with the pump medium. In particular, the voltage between the driven electrodes and the membrane must not drop directly across the pump medium.
Because the capacity between individual electrodes and the membrane in the arched areas differs considerably from the capacity in the areas adjoining below, the pumping process can be monitored electronically. Controlled metering of the smallest quantity of liquid is possible.
Another advantage is that the membrane is under compressive stress, that is, bulges in sub-areas without any actuation (spontaneous bulging), so that because it is less necessary for the membrane to expand, less force has to be expended to move the arched areas, serving as a seal, inside the cavity. When the membrane is under compressive stress, less force is needed to form the defined bulges, since sub-areas of the membrane are already bulged downwards and thus, in these areas, no force has to be generated to stretch the membrane in the direction of the cavity. Then the pump can be driven with significantly less voltage; and the result is a bistable valve, whose switching states can be held without power.
The present invention is described below with reference to the embodiments and the drawings without restricting the general inventive idea.

Fraunhofer Gesellschaft zur Forderung der angewandten Forschung e.V.


The present invention relates to a process for improving the pour point of a feed including paraffins containing more than 10 carbon atoms. Desirably, the feed to be treated is brought into contact with a catalyst based on NU-85 zeolite, at least partially in its acid form, and at least one hydro-dehydrogenating element, at a temperature which is in the range 170xc2x0 C. to 500xc2x0 C., a pressure in the range 1 to 250 bar and at an hourly space velocity in the range 0.05 to 100 hxe2x88x921, in the presence of hydrogen in a proportion of 50 to 2000 l/l of feed.

The present invention concerns a process for improving the pour point of feeds containing linear and/or slightly branched, long (more than 10 carbon atoms) paraffins, to provide good yields on converting feeds with high pour points to at least one cut with a low pour point and a high viscosity index for oil bases.
The present invention also concerns a NU-85 zeolite from which a portion of the elements Al, Fe, Ga or B has been removed, for example dealuminated, a catalyst containing that zeolite, its use in converting hydrocarbons, and a process for reducing the pour point using that catalyst.
High quality lubricants are fundamentally important for the proper operation of modern machines, automobiles and trucks. However, the quantity of paraffins originating directly from untreated crude oil with properties which are suitable for use in good lubricants is very low with respect to the increasing demand in this sector.
Heavy oil fractions containing large amounts of linear or slightly branched paraffins must be treated in order to obtain good quality oil bases in the best possible yields, using an operation which aims to eliminate the linear or slightly branched paraffins from feeds which are then used as base stock, or as kerosene or jet fuel.
High molecular weight paraffins which are linear or very slightly branched which are present in the oils or kerosene or jet fuel result in high pour points and thus in coagulation for low temperature applications. In order to reduce the pour points, such linear paraffins which are not or are only slightly branched must be completely or partially eliminated.
This operation can be carried out by extracting with solvents such as propane or methyl ethyl ketone, termed dewaxing, with propane or methyl ethyl ketone (MEK). However, such techniques are expensive, lengthy and not always easy to carry out.
A further technique is selective cracking of the longest linear paraffin chains to form compounds with a lower molecular weight, part of which can be eliminated by distillation.
Because of their form selectivity, zeolites are among the most widely used catalysts. The idea underlying their use is that zeolitic structures exist which have pore openings which allow long linear or very slightly branched paraffins to enter their micropores but which exclude branched paraffins, naphthenes and aromatic compounds. This phenomenon leads to selective cracking of linear or very slightly branched paraffins.
Zeolite based catalysts with intermediate pore sizes such as ZSM5, ZSM-11, ZSM-12, ZSM-22, ZSM-23, ZSM-35 and ZSM-38 have been described for their use in such processes.
The present invention proposes a pour point reduction process based on NU-85 zeolite.
Further, processes using some of such zeolites (ZSM-5, ZSM-11, ZSM-12, ZSM-22, ZSM-23, ZSM-35 and ZSM-38) can produce oils by cracking feeds containing less than 50% by weight of linear or linear or very slightly branched paraffins. However, for feeds containing higher quantities of these compounds, it has become apparent that cracking them leads to the formation of large quantities of products with lower molecular weights such as butane, propane, ethane and methane, which considerably reduces the yield of desired products.
In order to overcome these disadvantages, we have concentrated our research on developing catalysts based on NU-85 zeolites which also encourage isomerisation of such compounds.
The invention provides a process for improving the pour point of a paraffinic feed comprising paraffins containing more than 10 carbon atoms, in which process the feed to be treated is brought into contact with a catalyst based on NU-15 zeolite and at least one hydro-dehydrogenating element, at a temperature which is in the range 170xc2x0 C. to 500xc2x0 C., a pressure in the range 1 to 250 bar and an hourly space velocity in the range 0.05 to 100 hxe2x88x921, in the presence of hydrogen in a proportion of 50 to 2000 l/l of feed.
NU-85 in its hydrogen form, termed H-NU-85, obtained by calcining and/or ion exchanging as synthesised NU-85, used in the process of the invention, to and its synthesis are described in European patent EP-A2 0 462 745. This NU-85 is a hybrid of EU-1 and NU-87 zeolites.
The composition of this NU-85 zeolite, expressed as its anhydrous form, in terms of molar ratios of the oxides, has the following formula:
100xc3x97O2: 10 or less Y2O3: 20 or less R2/nO
where R represents one or more cations with valency n, X represents silicon and/or germanium, Y represents one or more of the following: aluminium, iron, gallium, boron, titanium, vanadium, zirconium, molybdenum, arsenic, antimony, chromium or manganese, preferably Al, Fe, Ga, B (elements T).
This NU-85 zeolite comprises crystals with an X ray diffraction diagram which has the characteristic lines of EU-1- and NU-87 zeolites and these peaks have between them a continuity and are characteristic of a continuous crystalline framework.
In its as synthesised state, i.e., prepared by synthesis, this NU-85 zeolite also comprises network images (obtained using a transmission electron microscope) which, in the orientation producing 20xc2x10.2 xc3x85 fringes for EU-1-zeolite, exhibits intermediate fringes of 12.5xc2x10.2 xc3x85 in association with those fringes of 20xc2x10.2 xc3x85, and/or an X ray diffraction diagram containing the lines shown in the following table:
The term xe2x80x9cNU-85 zeolitexe2x80x9d encompasses a family of products in which the NU-87 and EU-1 contents can vary substantially depending on the conditions selected to synthesis the NU-85 zeolite. Thus, and as is well known to the skilled person, the intensity of these lines can vary depending on the form of the zeolite, without raising doubts as to whether that zeolite belongs to the NU-85 family.
The process can advantageously convert a feed with a high pour point to a product with a lower pour point. It can be applied to reducing the pour point of gas oils, for example. It can also be used to convert heavier feeds to oils with a high viscosity index.
Among others, the feed is composed of linear and/or slightly branched paraffins containing at least 10 carbon atoms, preferably 15 to 20 carbon atoms, and advantageously 15 to 40 carbon atoms. Heavy feeds (to produce oils) contain paraffins essentially containing more than 30 carbon atoms; gas oils contain paraffins containing 10-30 carbon atoms.
The isomerised products present in the final products may contain about 65% to 80% of single-branched products and about 20% to 35% of multi-branched products. The term xe2x80x9csingle-branched productsxe2x80x9d means linear paraffins comprising a single methyl group, and the term xe2x80x9ctwo-branched productsxe2x80x9d means linear paraffins containing 2 methyl groups which are not carried by the same carbon atom. Thus xe2x80x9cmulti-branchedxe2x80x9d paraffins can be defined by extension.
Further, the catalyst comprises at least one hydro-dehydrogenating function, for example a group VIII metal (noble or non-noble) or a combination of at least one group VIII (non noble) metal or compound and at least one group VI metal or compound, and the reaction is carried out under conditions which will be described below.
Using the NU-85 zeolite of the invention under the conditions described above can produce products with a low pour point in good yields, with a high viscosity index for oils.
NU-85 zeolite has an Si/T atomic ratio in the range 5 to 600 and in particular in the range 10 to 300.
The global Si/T ratio of the zeolite and the chemical composition of the samples are determined by X ray fluorescence and atomic absorption,
The NU-85 zeolite used in the process of the invention can be obtained with the desired Si/T ratio for the catalytic application of the invention directly by synthesis by adjusting the operating conditions for synthesis. Then the zeolite is calcined and exchanged by at least one treatment using a solution of at least one ammonium salt to obtain the ammonium form of the zeolite which, once calcined, leads to the hydrogen form of the zeolite.
Advantageously, in other cases the NU-85 zeolite has undergone a treatment aimed at eliminating (removing) a portion of elements T, for example aluminium (in which case it is dealumination) so as to increase the low Si/T ratio obtained on synthesis. The global Si/T ratio is at least 18, preferably at least 20, or better at least 22 or even over 30, and generally NU-85 zeolites are used with Si/Al ratios of at most 600, preferably at most 300, or even at most 150.
This zeolite is obtained from as synthesised zeolite and thus contains silicon and an element T selected from the group formed by Al, Fe, Ga and B. A portion of elements T have been removed from the zeolite framework and advantageously they are extracted from the sample (they then pass into solution in the case of acid attack). In this advantageous case, the global Si/T atomic ratio of the zeolite is greater than that of the starting zeolite, the difference (increase) is at least equal to 10% of the Si/T ratio of the starting zeolite. The surface Si/T atomic ratio (obtained by XPS) does not diminish, and advantageously it increases.
The zeolite constitutes a further aspect of the invention.
The dealuminated NU-85 zeolite of the invention, in the preferred case where T is Al, can be prepared using two dealumination methods from as synthesised NU-85 zeolite containing an organic structuring agent. These methods are described below. However, any other method which is known to the skilled person can also be used. These methods described for Al can also be used for other elements T.
The first (preferred) method, direct acid attack, comprises a first calcining step carried out in dry air, at a temperature which is generally in the range 450xc2x0 C. to 550xc2x0 C., which eliminates the organic structuring agent present in the micropores of the zeolite, followed by a step in which the zeolite is treated with an aqueous solution of a mineral acid such as HNO3 or HCl or an organic acid such as CH3CO2H. This latter step can be repeated as many times as is necessary to obtain the desired degree of dealumination. Between these two steps, one or more ion exchange steps can be carried out using at least one NH4NO3 solution, to at least partially and preferably almost completely eliminate the alkaline cation, in particular sodium. Similarly, at the end of the direct acid attack dealumination step, one or more optional ion exchange steps can be carried out using at least one NH4NO3 solution to eliminate residual alkaline cations, in particular sodium.
In order to obtain the desired Si/Al ratio, the operating conditions must be correctly selected; tile most critical parameters in this respect are the temperature of the treatment with the aqueous acid solution, the concentration of the latter, its nature, the ratio between the quantity of acid solution and the mass of the treated zeolite, die treatment period and the number of treatments carried out.
Dealumination can also be achieved using chemical dealuminating agents such as (by way of non exhausting examples) silicon tetrachloride (SiCl4), ammonium hexafluorosilicate [(NH4)2SiF6], ethylenediaminetetraacetic acid (EDTA) and its mono and disodium forms. These reactants can be used in solution of in the gaseous phase, for example in the case of SiCl4.
The second method, heat treatment (in particular using steam, by steaming)+acid attack, comprises firstly calcining in dry air at a temperature which is generally in the range 450xc2x0 C. to 550xc2x0 C., to eliminate the organic structuring agent occluded in the micropores of the zeolite. The solid obtained then undergoes one or more ion exchanges using at least one NH4NO3 solution, to eliminate at least a portion, preferably practically all of the alkaline cation, in particular sodium, present in the cationic position of the zeolite. The zeolite obtained then undergoes at least one framework dealumination cycle comprising at least one heat treatment which is optionally and preferably carried out in the presence of steam, at a temperature which is generally in the range 500xc2x0 C. to 900xc2x0 C., and optionally followed by at least one acid attack using an aqueous solution of a mineral or organic acid as defined above. The conditions for calcining in the presence of steam (temperature, steam pressure and treatment period), also the post-calcining acid attack conditions (attack period, concentration of acid, nature of acid used and the ratio between the volume of the acid and the mass of zeolite) are adapted so as to obtain the desired level of dealumination. For the same reason, the number of heat treatment-acid attack cycles can be varied.
In a variation of this second method, the acid attack step, i.e., treatment using a solution of an acid, can be replaced by treatment with a solution of a chemical dealuminating compound such as those cited above, for example, namely silicon tetrachloride (SiCl4), ammonium hexafluorosilicate [(NH4)2SiF6], ethylenediaminetetraacetic acid (EDTA) and its mono and disodium forms.
In the preferred case when T is Al, the framework dealumination cycle, comprising at least one heat treatment step, optionally and preferably carried out in the presence of steam, and at least one attack step carried out in an acid medium of the NU-85 zeolite, can be repeated as often as is necessary to obtain the dealuminated NU-85 zeolite having the desired characteristics. Similarly, following the heat treatment, optionally and preferably carried out in the presence of steam, a number of successive acid attacks can be carried out using different acid concentrations.
In a variation of this second calcining method, heat treatment of the NU-85 zeolite containing the organic structuring agent can be carried out at a temperature which is generally in the range 500xc2x0 C. to 850xc2x0 C., optionally and preferably in the presence of steam. In this case, the steps of calcining the organic structuring agent and dealumination of the framework are carried out simultaneously. The zeolite is then optionally treated with at least one aqueous solution of a mineral acid (for example HNO3 or HCl) or an organic acid (for example CH3CO2H). Finally, the solid obtained can optionally undergo at least one ion exchange step using at least one NH4NO3 solution, to eliminate practically all of the alkaline cations, in particular sodium, present in the cationic position in the zeolite.
The NU-85 zeolite of the invention is at least partially, preferably practically completely, in its acid form, i.e., in its hydrogen (H+) form. The Na/T atomic ratio is generally less than 10%, preferably less than 5%, and more preferably less than 1%.
The catalyst of the invention contains NU85 zeolite with an Si/T ratio of at least 18, which may or may not be mixed with a matrix, and optionally at least one hydro-dehydrogenating elements which is a noble metal or a combination of at least one group VI metal or compound and at least one group VIII metal or compound.
The catalyst used in the process of the invention generally contains at least one hydro-dehydrogenating element, for example at least one group VIII element, preferably a noble metal, advantageously selected from the group formed by Pt or Pd, which is introduced into the molecular sieve by dry impregnation or ion exchange, for example, or by any other method which is known to the skilled person, or it is introduced into the matrix.
The amount of metal thus introduced, expressed as weight % with respect to the mass of molecular sieve engaged, is generally less than 5%, preferably less than 3%, and the amount of noble metal in the catalyst is generally less than 2% by weight.
The hydro-dehydrogenating element can also be a combination of at least one group VI metal or compound (for example molybdenum or tungsten) and at least one group VIII metal or compound (for example nickel or cobalt). The total concentration of group VI and group VIII metals, expressed as the metal oxides with respect to the support, is generally in the range 5% to 40% by weight, preferably in the range 7% to 30% by weight. The weight ratio (expressed as the metallic oxides) of group VIII metals to group VI metals is preferably in tie range 0.05 to 0.8: more preferably in the range 0.13 to 0.5.
The element can also be rhenium and/or niobium, used alone or in combination with the group VIII and/or VI elements.
This type of catalyst can advantageously contain phosphorous, the content of which is generally less than 15% by weight, preferably less than 10% by weight, expressed as phosphorous oxide P2O5 with respect to the support.
When treating a real feed, the molecular sieve of the invention is first formed. In a first variation, the molecular sieve can have at least one hydro-dehydrogenating element deposited on it, and it can be formed by any technique which is known to the skilled person. In particular, it can be mixed with a matrix, which is generally amorphous, for example a moist alumina gel powder. The mixture is then formed, for example by extrusion through a die. The amount of molecular sieve in the mixture obtained is generally in the range 0.5% to 99.9%, advantageously in the range 5% to 90% by weight, with respect to the mixture (molecular sieve+matrix) and preferably in the range 10% to 90%, more preferably in the range 20% to 70%.
In the remaining text, the tern xe2x80x9csupportxe2x80x9d is used to describe the molecular sieve+matrix mixture.
Forming can be carried out with matrices other than alumina, such as magnesia, amorphous silica-aluminas, natural clays (kaolin, bentonite, sepiolite, attapulgite), silica, titanium oxide, boron oxide, zirconia, aluminium phosphates, titanium phosphates, zirconium phosphates, coal and mixtures thereof. Techniques other than extrusion, such as pelletization or bowl granulation, can be used.
The group VIII hydrogenating metal, preferably Pt and/or Pd, can also be deposited on the support using any process which is known to the skilled person which can deposit metal on the molecular sieve. Competitive cation exchange can be used, with ammonium nitrate as the preferred competitor; the competition ratio being at least about 20 and advantageously about 30 to 200. When platinum or palladium is used, a platinum tetramine complex or a palladium tetramine complex is normally used: these latter are almost completely deposited on the molecular sieve. This cation exchange technique can also be used to deposit the metal directly on powdered molecular sieve before mixing it with any matrix.
Deposition of the group VIII metal(s) is generally followed by calcining in air or oxygen, usually between 300xc2x0 C. and 600xc2x0 C. for 0.5 to 10 hours, preferably between 350xc2x0 C. and 550xc2x0 C. for 1 to 4 hours. Reduction in hydrogen can then follow, generally at a temperature which is in the range 300xc2x0 C. to 600xc2x0 C. for 1 to 10 hours, preferably in the range 350xc2x0 C. to 550xc2x0 C. for 2 to 5 hours.
The platinum and/or palladium can also be deposited not directly on the molecular sieve, but on the matrix (alumina binder) before or after forming, by anion exchange with hexachloroplatinic acid, hexachloropalladic acid and/or palladium chloride in the presence of a competing agent, for example hydrochloric acid. As before, after depositing the platinum and/or palladium, the catalyst is generally calcined then reduced in hydrogen as indicated above.
The non noble group VIII metals or an association of oxides of non noble group VI and VIII metals, comprising the hydro-dehydrogenating function, can be introduced into the catalyst at various stages of the preparation and in various fashions.
It can be introduced only in part (for associations of group VI and VIII metals) or completely on mixing the molecular sieve of the invention with the gel of the oxide selected as the matrix. It can be introduced using one or more ion exchange operations on the calcined support constituted by the molecular sieve of the invention dispersed in the selected matrix, using solutions containing the precursor salts of the selected metals when these belong to group VIII. They may be introduced by one or more impregnation operations carried out on the formed and calcined support, using a solution of precursors of oxides of metals from group VIII (in particular cobalt or nickel) when the precursors of oxides of metals from group VI (in particular molybdenum or tungsten) have first been introduced on mixing the support. Finally, it can be introduced by one or more impregnation operations carried out on the calcined support constituted by a molecular sieve of the invention and the matrix, using solutions containing the precursors of the oxides of metals from groups VI and/or VIII, the precursors of oxides from group VIII metals preferably being introduced after those of group VI or at the same time as the latter.
When the metal oxides are introduced in a plurality of impregnation steps using the corresponding precursor salts, an intermediate calcining step must be carried out at a temperature in the range 250xc2x0 C. to 600xc2x0 C.
Molybdenum impregnation can be facilitated by adding phosphoric acid to the ammonium paramolybdate solutions.
The mixture is then formed, for example by extrusion through a die. The amount of molecular sieve in the mixture obtained is generally in the range 0.5% to 99.9%, advantageously in the range 10% to 90% by weight with respect to the mixture (molecular sieve+matrix), preferably in the range 20% to 10%.
Deposit of the final metal is generally followed by calcining in air or in oxygen, usually between 300xc2x0 C. and 600xc2x0 C. for 0.5 to 10 hours, preferably between 350xc2x0 C. and 550xc2x0 C. for 1 to 4 hours.
It is then generally followed by suppuration of the catalyst before bringing it into contact with the feed, using any method known to the skilled person. Thus in this case the catalyst advantageously contains sulphur.
The catalyst of the invention is used to convert hydrocarbons, in particular to reduce the pour point as will be defined below.
The process for reducing the pour point as defined below can also be carried out using a catalyst containing a NU-85 zeolite, obtained by synthesis, with the formula described above, in particular with a Si/T ratio of 5 to 600, advantageously 10 to 300. Zeolites with Si/T ratios of less than 20 are thus included.
Feeds which can be treated using the process of the invention are advantageously fractions with relatively high pour points which are to be reduced.
The process of the invention can be used to treat a variety of feeds from relatively light fractions, such as kerosenes and jet fuels, to feeds with higher boiling points such as middle distillates, vacuum residues, gas oils, middle distillates from FCC (LCO and HCO) and hydrocracking residues.
The feed to be treated is, for the most part, a C10 cut with an initial boiling point of more than about 175xc2x0 C., preferably a heavy cut with a boiling point of at least 280xc2x0 C., advantageously a boiling point of at least 380xc2x0 C. The process of the invention is particularly suitable for treating paraffinic distillates such as middle distillates which encompass gas oils, kerosenes, jet fuels, vacuum distillates and all other fractions with a pour point and viscosity which must be adapted to satisfy specifications.
Feeds which can be treated using the process of the invention call contain paraffins, olefins, naphthenes, aromatics and heterocycles and have a high proportion of high molecular weight n-paraffins and very slightly branched paraffins, also of high molecular weight.
The reaction is carried out so that the cracking reactions remain sufficiently low to render the process economically viable. The amount of cracking reactions is generally below 40% by weight, preferably below 30%, and advantageously below 20%.
Typical feeds which can advantageously be treated by the process of the invention generally have a pour point of more than 0xc2x0 C. The products resulting from treatment in accordance with the process have pour points of below 0xc2x0 C., preferably below about xe2x88x9210xc2x0 C.
These feeds contain amounts of n-paraffins and very slightly branched paraffins containing more than 10 carbon atoms, also with high molecular weight, of over 30% and tip to about 90%, and in some cases more than 90% by weight. The process is of particular interest when this proportion is at least 60% by weight.
Non limiting examples of other feeds which can be treated in accordance with the invention are bases for lubricating oils, synthesised paraffins from the Fisher-Tropsch process, high pour point polyalphaolefins, synthesised oils, etc . . . The process can also be applied to other compounds containing an n-alkane chain such as those defined above, for example n-alkylcycloalkanes, or containing at least one aromatic group.
The process is carried out under the following operating conditions:
the reaction temperature is in the range 170xc2x0 C. to 500xc2x0 C., preferably in the range 180xc2x0 C. to 470xc2x0 C., advantageously 190xc2x0 C. to 450xc2x0 C.;
the pressure is in the range 1 to 250 bar, preferably in the range 10 to 200 bar;
the hourly space velocity (HSV expressed as the volume of feed injected per unit volume of catalyst per hour) is in the range about 0.05 to about 100, preferably about 0.1 to about 30 hxe2x88x921.
The feed and the catalyst are brought into contact in the presence of hydrogen. The amount of hydrogen used, expressed in liters of hydrogen per liter of feed, is in tie range 50 to about 2000 liters of hydrogen per liter of feed, preferably in the range 100 to 1500 liters of hydrogen per liter of feed.
The quantity of nitrogen compounds in the feed to be, treated is preferably less than about 200 ppm by weight, more preferably less than 100 ppm by weight. The sulphur content is below 1000 ppm by weight, preferably less than 500 ppm, more preferably less than 200 ppm by weight. The quantity of metals in the feed, such as Ni or V, is extremely low, i.e., less than 50 ppm by weight, preferably less than 10 ppm by weight and more preferably less than 2 ppm by weight.
The compounds obtained using the process of the invention may contain single-branched, two-branched and multi-branched compounds, advantageously with methyl groups.

NU-85 zeolite catalyst and a process for improving the pour point of feeds containing paraffins


Low pressure sensing and imperviousness to corrosion and to the effects of harsh environments are achieved in a pressure sensor that employs a flexible membrane supporting piezoresistive elements. A plurality of piezoresistive elements are aligned substantially collinearly across one surface of the flexible membrane. Innermost piezoresistive elements are disposed in such a way that they experience tension in response to an applied pressure, whereas outermost piezoresistive elements are disposed in such a way that they experience compression in response to the same applied pressure. Contact pads for each end of each piezoresistive element allow the elements to be configured in any number of desirable arrangements. In one exemplary embodiment, four piezoresistive elements are disposed along a main central axis of the membrane. The contacts of the elements are connected to form a Wheatstone bridge. Conventional Wheatstone bridge techniques are utilized to convert an applied pressure into an output electrical signal. The membrane includes amorphous or nanocrystalline semiconductor layers grown on a flexible substrate such as Kapton or suitable plastic materials.

1. Field of the Invention
This invention relates to the field of pressure sensors and, more particularly, to thin-film pressure sensors adapted for low pressure sensing applications.
2. Description of the Related Art
Pressure sensors have wide applicability today from microphones, household electronics, and simple vacuum sensing applications to biomedical instrumentation, wind tunnel, and automotive performance applications. Many of these devices depend on integrated sensor technology that utilizes the piezoresistive effect. Simply put, the piezoresistive effect is one in which the resistance of an element changes as a result of length changes for that element generally as a result of stress. Resistance changes can behave anisotropically in directions parallel to and perpendicular to the direction of the stress.
It is well known in sensor technology to employ a Wheatstone bridge arrangement of piezoresistors to sense pressure and pressure changes. The arrangement commonly chosen involves four piezoresistors located at four distinct edges of a pressure sensing membrane that is supported on a substrate. Generally, the position chosen for each resistor is one where the stress is greatest when vertical pressure is applied to the membrane at its the center or uniformly across the membrane surface. In these designs, orientation of the piezoresistors is also important. Usually, two piezoresistors are oriented parallel to the direction of stress so that their resistance increases with increasing pressure and the other two piezoresistors are oriented perpendicular to the direction of stress so that their resistance decreases with increasing pressure. See, for example, C. Malhaire et al., "Design of a polysilicon-on-insulator pressure sensor with original polysilicon layout for harsh environment," Thin Solid Films, No. 427, pp. 362–366 (2003) and U.S. Pat. No. 6,700,174 issued to Miu et al. on Mar. 2, 2004.
Most proposed designs known in the art include rigid substrates. This limits the applicability of such pressure sensors to relatively high pressure environments. Many of the rigid substrates commercially known utilize metallic membranes such as stainless steel. These membranes are easily damaged in severe natural or corrosive environments.


As subject of the present invention, a woven composite fabric, comprising metal elements and polymer elements is provided. The metal elements being metal wires, bundles of metal wires, metal strands or metal cords. According to the invention, the polymer elements are polymer tapes, having a substantially rectangular cross-section.

Flexible reinforced tubes and hoses are widely known in the art.
A method to produce such reinforced tubes and hoses, comprises the steps of winding reinforcing material round a polymer tube or hose or round a mandrel. E.g. U.S. Pat. No. 3,930,091 shows such method to provide a reinforced tube, winding glasfibers round a mandrel.
When metal elements, being metal wires, bundles of metal wires, metal cords or metal strands are to be used to reinforce a tube or hose, a polymer strip, comprising metal elements running essentially in the longitudinal direction of the strip may be used. Such strips are wound round a polymer tube or on a mandrel. Afterwards, after providing the reinforcing layers, the polymer is to be heated to ensure the adhesion of the polymer layers to each other and eventually to the polymer tube supporting the reinforcing layers.
The advantage of the use of such strips is that only one or a few strips are to be controlled during production of the reinforced tube or hose, rather than controlling individually a large set of metal elements during production.
The present invention relates to disadvantages, which may be met using such polymer strips, comprising metal elements in longitudinal direction. These disadvantages are mainly that no polymer material can make contact with a metal element of an adjacent layer, when two (or more) layers of such strips are wound on top of each other. Further, due to the necessary thickness of the polymer material surrounding the metal elements, a minimum thickness of the reinforcing layer is provided, which for some applications still is too thick. Too much than necessary polymer material may be present between different layers of metal elements.

This patent is subject to a terminal disclaimer.


Process for the manufacture of furfural wherein a pentosan-containing raw material acidified or not, is heated to a temperature T1 by admitting steam through valve 2 while the valves 3 and 4 are closed. During the very short heating process, the steam condenses, thus increasing the moisture content of the charge. Then, valve 2 is closed and a leak valve 3 is opened so as to produce a steady small flow of product vapor by gradual depressurization. This causes a slow drop in temperature. When a suitably chosen temperature T2 is reached, the leak valve 3 is closed to terminate the first xe2x80x9cgradual depressurizationxe2x80x9d. If at the end of this period no more furfural was obtained, the digestion is completed by opening valve 4 to discharge the residue. If, however, furfural was still obtained, the reactor is reheated and submitted to another xe2x80x9cgradual depressurizationxe2x80x9d period.

This invention relates to a process for the manufacture of furfural.
Chemical reactors must be designed to suit the characteristics of the process intended. In making furfural, this has not been the case. For the first industrial production of furfural, QUAKER OATS used reactors from an abandoned cereal process as they happened to be available, and such reactors leave been used ever since. Later, ROSENLEW and ESCHER WYSS built furfural plants based on reactors designed for making wood pulp. None of the industrial furfural reactors employed today were conceived to meet the special requirements of furfural production, and it is, therefore, not surprising that the yields obtained with these reactors do not even exceed 60%.
The principal yield losses are caused by a reaction between furfural and xylose, so that striving for a high yield forbids having furfural and xylose in the same place. All existing furfural reactors violate this requirement. By pointedly eliminating this deficiency, the process here described permits attaining yields in the order of 100%.
In analytical chemistry, the conversion of pentosan or pentose to furfural is used for a quantitative determination of these substances. This is possible as it was shown that in this procedure the furfural yield is a proven 100%. The procedure consists in an atmospheric digestion of pentosan or pentose in 12% aqueous HCl saturated with NaCl. By contrast, in the present industrial furfural processes mentioned above, a pressure reactor is used to submit the raw material to a steam treatment. By condensing, the steam effects heating to a constant temperature, and by passing through the raw material, it entrains furfural produced therefrom. The furfural reaction is catalysed either by added mineral acid or by various carboxylic acids (mainly acetic acid and formic acid) formed from the raw material. As compared to the analytical furfural process, a fundamental difference lies in the fact that in the latter process an appropriate heat input maintains the reaction medium in a state of boiling, whereas in the industrial processes at any pressure a condensation of steam is thermodynamically incapable of bringing the reaction medium, a pentose solution to boiling, because of the boiling point elevation caused by the xylose. The difference is illustrated schematically in FIG. 1 showing phase diagrams for furfural in an aqueous solution boiling at 110xc2x0 C. (12% HCl saturated with NaCl), and in an aqueous solution boiling at 101xc2x0 C. (xylose solution). If a small furfural concentration xcex6 is generated in the first system representing the analytical furfural process, this leads to point A lying in the vapour field, which means that any furfural formed in this boiling solution will be instantly transformed to vapour where it cannot react with pentose as the latter is not volatile. Consequently, in this case, loss reactions between furfural and pentose are impossible, which explains the proven yield of 100%.
On the other hand, if a small furfural concentration xcex6 is generated in the second system, and if this system is heated by condensing steam at atmospheric pressure, this leads to point B lying in the liquid field. Hence, in the present industrial furfural reactors the reaction medium is not brought to boiling, so that the furfural remaining in solution can react with pentose to form furfural pentose, which explains the known high yield losses. The entrainment of furfural vapour by the steam flow does not change this statement to any significant extent, since this entrainment is a slow and inefficient process giving the loss reactions in the liquid phase plenty of time to take place.
As the principal difference between the analytical furfural process of 100% yield and the industrial processes of less than 60% yield lies in the fact that in the first case the reaction medium is boiling while in the second case it is not boiling, it was compelling to create an industrial process in which the reaction medium is maintained in a state of boiling. In view of the fact that with giant furfural reactors, charged with solids not conductive to being stirred, an indirect energy input by heating the walls can be ruled out, it is the essence of this invention to bring about continuous boiling by a gradual (slow) depressurization. In this fashion, a uniform boiling down to molecular dimensions is enforced without a need for mixing.
Apart from the poor yields achieved, the present commercial processes available are extremely expensive to operate. This is due to the large quantities of steam required. typically 30 to 50 tons of steam per ton of furfural produced, and also the lengthy reaction times of between 2 and 5 hours.
It is therefore an object of this invention to provide a manufacturing process which not only produces a greater yield, but also requires a lower input of steam per ton of furfural produced and results in a shorter reaction time.
According to the invention, a process for the manufacture of furfural includes the steps of charging a reactor with a pentosan containing material, acidified or not, heating the charge by introduction of pressurized steam to a first predetermined temperature, closing the steam inlet valve of the reactor and subjecting the charge to a gradual reduction of pressure until a second predetermined temperature is attained, the depressurization maintaining the liquid phase within the reactor in a constantly boiling state.
In the preferred form the rate of depressurization is sufficient to complete the conversion to furfural before a second predetermined temperature is attained. Also in the preferred form of the invention, the charge is acidified prior to heating.
Also in the preferred form of the invention, the gradual depressurization comprises the controlled leaking of a stream of vapour from the reactor until the second predetermined temperature is attained.
In one form of the invention, a first depressurization is followed by a reheating to a temperature at or near the first predetermined temperature, the reheating being followed by a second gradual depressurization.
Subsequent reheating and depressurization cycles may also be employed if required.
In one form, steam may be added during depressurization to increase the reaction temperature and improve yield.
In the preferred form of the invention, the charge material may be in solid or liquid form. Bagasse from sugar cane is a common feed and may be added to the reactor in solid or slurry form.
Also in the preferred form of the invention the gradual depressurization takes place in the temperature range between 280xc2x0 Celsius and 150xc2x0 Celsius, however the preferred range of operation is between 230xc2x0 Celsius and 170xc2x0 Celsius.
By an appropriate choice of the first and second temperatures, and by appropriate selection of a mineral or organic acid concentration, it is possible, if desired, to complete the process in a single depressurization period since high temperatures and high acidity result in a short reaction time.
In the preferred form of the invention, phosphoric acid is used as the catalyst.
An apparatus for use in a process according lo the invention comprises a pressure reactor including an inlet for steam under pressure, and an outlet for condensate vapour, the inlet and outlet including one or more valves for controlling the flow rate therethrough.
The outlet includes, after a valve, an orifice plate of predetermined dimensions for assisting in controlling the rate of depressurization. In this form, the valve and orifice plate may be operated in tandem to obtain a range of depressurization rates or a flow control valve governed by temperature or pressure can be used.
In any form of the invention the reactor may be thermally well insulated.
In an alternative form of the invention the reactor walls are designed to be heated. Also in this form, all valve operations are preferably controlled automatically by a computerized control unit. It has been demonstrated experimentally, on a pilot plant scale, that by maintaining the liquid phase of the reaction medium in a state of boiling throughout the reaction period, the furfural yield obtained is substantially greater than current commercial processes, and if correctly controlled may approach yields achieved in the analytical furfural process. The Applicant contends further that apart from increasing the yield, the process of the invention is operable at substantially lowered capital and production costs, for the following reasons:
(1), The process of the invention does not use steam for stripping furfural from the mass of feed material as once the reactor is sufficiently heated, the steam inlet is closed. Further steam will only be required briefly if a reheating cycle is employed.
(2), As a result of the non-use of steam to strip the furfural, the volume of condensate existing the reactor is significantly reduced and the concentration of furfural therein will be proportionately increased in relation to existing processes. This increased furfural concentration will greatly simplify the primary azeotropic distillation. In special cases, for instance in the application of the furfural as a nematicide, no distillation is needed at all.
(3), The product of the invention contains less acetic and formic acid (formed from the raw material) since, after reaching the second predetermined temperature of the decompression, most of these by-products are discharged with the residue. This greatly reduces the loading of the effluent generated by the plant.

International Furan Technology (PTY) Limited