A composition for treating inflammation and pain in mammals, particularly humans. Effective amounts of a boswellic acid, a curcuminoid, a gingerol, a capsaicinoid, a bioflavonoid, and a vitamin C source, in various combinations, all preferably from a botanical source, are blended to form a dose for oral administration. Administration of the dose provides relief from pain and inflammation of connective tissue. The dose may be administered as a tablet, a liquid, or a powder.

1. The Field of the Invention
This invention relates compositions and methods used to prevent and treat inflamation in mammals. More particularly, the present invention relates to compositions and methods for reducing inflamation and pain associated with acute inflammation of mammalian body parts, particularly joints, due to injury or due to arthritic conditions or other disease conditions.
2. The Background Art
Millions of people and animals suffer pain due to inflamation of connective tissue, including joints and other body parts. The suffering which is encountered ranges from mild soreness to debilitating pain which prevents any motion of the afflicted body part.
The term xe2x80x9cconnective tissuexe2x80x9d loosely refers to the tissues which hold a body together. Connective tissue disease is the term used to generally describe a long list of afflications which involve connective tissue. Connective tissue is present in all organs, so the term connective tissue diseases describes a group of diseases which influence a wide range of different body systems.
Rheumatic diseases, which are one type of connective tissue disease, include a variety of different conditions. However, a common feature a rheumatic diseases is that they all involve joints and the surrounding tissues such as ligaments, tendons and muscles. Rheumatic diseases can involve other, seemingly unrelated organs as well, such as eyes, skin and glands. Rheumatic diseases are usually divided into those that primarily involve joints, known as arthritis, and those involving other tissues, generally referred to connective tissue diseases. Arthritis is further subdivided into inflammatory and non-inflammatory arthritis.
One of the most common forms of connect tissue disease is osteoarthritis which is a non-inflammatory type of arthritis. Osteoarthritis is generally considered to be due to xe2x80x9cwear and tearxe2x80x9d of the joints leading to damage of the joint surfaces which results in pain on movement of the joint. There are many factors influencing development of osteoarthritis, including a family history of osteoarthritis and previous damage to the joint caused by injury or surgery. Osteoarthritis is very common in older age groups, but can afflict younger people and animals.
Symptoms in osteoarthritis tend to get worse with activity, so that the greatest pain is experienced at the end of the day. In contrast, the symptoms of inflammatory arthritis include the greatest pain occurring at the movement of a joint after a night""s sleep of inactivity. In the case of osteoarthritis, there may be hard, bony swelling of the joints, and a gritty feeling (or even noise) when the joint is moved.
The term arthritis also refers to conditions where inflamation occurs in a joint. While some in the field use the term xe2x80x9carthritisxe2x80x9d to strictly mean inflammation of the joints, the term is used more generally for almost all joint problems. So the term xe2x80x9cinflammatory arthritisxe2x80x9d generally means those diseases of joints where, for example, the immune system is causing inflammation in the joint. Among the more common types of inflammatory arthritis are rheumatoid arthritis, gout, psoriatic arthritis (associated with the skin condition psoriasis), reactive arthritis, viral or post-viral arthritis (occurring after an infection), and spondylarthritis which affects the spine as well as joints.
These different types of arthritis all have many features in common, so that it may be impossible to say exactly what type of arthritis a patient is afflicted with. This is especially true at the onset of arthritis, as the early symptoms are generally common to all types. As a rule, any type of arthritis can affect any joint, but some patterns of affected joints are typical of particular types of arthritis, as discussed below.
The characteristic symptoms of inflammatory arthritis are pain and swelling of one or more joints. The afflicted joints are often warmer than the other joints of the body. Stiffness of the joints when getting up in the morning, or after sitting still for a time, is very common and is sometimes the first symptom. These symptoms may begin after a minor illness such a sore throat or a cold, or may even be associated with a period of emotional stress such as a bereavement. Usually, however there is no identifiable cause associated with the commencement of inflammatory arthritis.
Moreover, there are many common minor pains which are not arthritis but are due to injury, strain or inflammation of tendons or ligaments and are referred to as xe2x80x9csoft tissue rheumatism.xe2x80x9d Some of the more common soft tissue rheumatism conditions which afflict humans include tennis elbow, frozen shoulder, carpal tunnel syndrome, plantar fasciitis, and Achilles tendonitis.
Tennis elbow is due to inflammation of the tendons of the hand gripping muscles where these tendons are attached to the elbow. This results in pain at the elbow, worse on gripping with the hand, and the afflicted area is tender when pressed. It usually gets better by itself if the hand is rested, but the condition can recur. Conventional treatment includes injection of steroids at the tender spot. As is well appreciated, tennis elbow is not confined to tennis players.
Frozen shoulder is a stiffening of the ligaments around the shoulder joint which usually comes on after prolonged unaccustomed use of the arm, such as painting a ceiling. When afflicted with frozen shoulder, it is painful and difficult to move an arm in any direction. In this condition, it is important to start treatment quickly since delay will make the condition more difficult to treat. Past treatment has included a program of exercises to slowly increase the range of movement of the arm with a steroid injection into the shoulder to get it moving again.
Carpal tunnel syndrome involves a nerve which passes through the carpal tunnel on the front of the wrist into the human hand. When this tunnel becomes inflamed it can press on the nerve causing shooting pain into the thumb and first two fingers. The syndrome can arise due to many conditions such as thyroid disease, pregnancy and arthritis. Symptoms are often worse at night keeping the sufferer awake. Past treatments include steroid injections and rest. In some cases, surgery to open up the tunnel may be necessary.
Plantar fasciitis involves ligaments in the sole of the foot which can get inflamed leading to pain on the bottom of the heel on walking. Steroid injections and orthotic shoe devices have been used to treat the condition.
Achilles tendonitis involves the Achilles tendon located at the back of the human ankle and which becomes inflamed and painful when walking or especially painful to stand up on tip-toe. This condition is usually caused by shoes which rub at the back of the heel. Further information regarding these afflictions can be obtained from Arthritis Foundation (see http://www.arthritis.org and the links provided thereat as of the filing of this application).
All of these conditions and afflictions are the subject of continuing research looking for better treatments. For many arthritis sufferers, an improved treatment would include one which does not require the consumption of over-the-counter or prescription drugs. Moreover, many people suffer from afflictions attacking organs such as the skin and muscles and expressing symptoms via headaches and backaches, all of which would benefit from better treatments. For example, treatments utilizing botanical compositions can benefit many patients and provide advantages not otherwise available.
In view of the above described state of the art, the present invention seeks to realize the following objects and advantages.
It is a primary object of the present invention to provide a composition used to treat mammals which reduces acute and chronic inflammation.
It is also an object of the present invention to provide a composition which is orally administered which reduces inflammation in mammals.
It is also an object of the present invention to provide a composition for use as a dietary supplement which, when ingested, is effective in treating the pain and discomfort of inflammatory ailments such as, but not limited to, rheumatoid arthritis, osteoarthritis, juvenile rheumatoid arthritis, soft tissue rheumatism, gout, low back pain, minor soft tissue injuries, minor burns and other skin injuries and afflictions, sprains, headache, backache, and general muscle soreness after exercise and exertion.
It is another object of the present invention to provide a composition for use as a dietary supplement which, when ingested on a regular basis, improves the use of joints which are afflicted with arthritis.
It is still another object of the present invention to provide a dietary supplement which reduces the swelling, pain and morning stiffness of arthritic joints and which increases range of motion, grip strength and general mobility in affected joints.
It is yet another object of the present invention to provide a dietary supplement composition which improves the general health, quality of life, and well being of those suffering from chronic inflammatory diseases, including rheumatism and arthritis.
It is a yet further object of the present invention to provide a safe and effective dietary supplement composition which can be used to reduce the dosage of, or replace conventional Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), for the symptomatic treatment of pain, inflammation and swelling in mammals.
It is also an object of the present invention to provide a safe and effective composition for the treatment of pain, inflammation and swelling in individuals for whom NSAIDs are no longer desirable due to gastrotoxicity, gut intolerance or risk of renal damage.
It is a further object of the present invention to provide a composition which is formulated using rigorously and correctly identified, analyzed, and documented botanical ingredients from which active ingredients have been water extracted to prepare a concentrate, which is dried, and which results in the end composition standardized to contain minimum levels of certain indicator phytochemicals having the desired physiological attributes.
These and other objects and advantages of the invention will become more fully apparent from the description and claims which follow, or may be learned by the practice of the invention.
The present invention provides a composition for treating inflamation and pain in mammals, particularly humans. In one preferred composition, an effective amount of a boswellic acid, the boswellic acid being derived from a botanical source, and an effective amount of a curcuminoid, the curcuminoid being derived from a botanical source, are blended to form a dose for oral administration to the human or other mammal. Administration of the dose provides relief from pain and inflamation of connective tissue.
In one preferred dose of the composition, the effective amount of boswellic acid comprises from about 10 to about 1800 milligrams of Boswellia gum extract and more preferably about 100 to about 800 milligrams of Boswellia gum extract. Other preferred sources of boswellic acid include extracts of: Boswellia serrata, Boswellia bhau-dajiana, Boswellia frereana, Boswellia papyrifera, Sudanese Boswellia sacra, and Boswellia carteri, Commiphora incisa, Commiphora myrrha, Commiphora abyssinica, Commiphora erthraea, Commiphora molmol, and Bursera microphylla. The extract providing the boswellic acid preferably comprises in the range from about 20% to about 40% by weight of the dose.
In the preferred dose of the composition, the effective amount of curcuminoid comprises from about 50 milligrams to about 400 milligrams of curcuminoids and more preferably about 100 milligrams to about 300 milligrams of curcuminoids. Preferably, the curcuminoids are contained in a tumeric rhizome extract. The extract providing the curcuminoid preferably comprises in the range from about 5% to about 40%, and more preferably from about 10% to about 30%, by weight of the dose.
In another preferred embodiment of the invention, the formulation can also contain an effective amount of gingerol, the gingerol being derived from a botanical source. The gingerol is preferably obtained from ginger rhizome extract. The amount of gingerol in the composition is preferably about 1 to about 200 mg, more preferably about 1 to about 100 mg, and most preferably about 2 to about 50 mg.
The preferred doses of the present invention may also include an effective amount of capsaicin, an effective amount of an antioxidant, an effective amount of flavonoids (for example, quercetin or isoquercetin), and/or an effective amount of vitamin C. The extract providing the capsaicinoid preferably comprises in the range from about 1% to about 25%, and more preferably from about 1% to about 15%, by weight of dose. The extract providing the bioflavonoid preferably comprises in the range from about 1% to about 25%, and more preferably from about 1% to about 20%, and most preferably from about 2% to about 20%, by weight of the dose. The dose may be administered as a tablet, a liquid, or a powder.
In another preferred embodiment of the invention, the present invention further comprises effective amounts of certain minerals, such as calcium and phosphorus. In tablet form, the present invention can further comprise additives for imparting satisfactory compression characteristics to the formulation, including diluents, binders, and lubricants, and for giving additional desirable physical characteristics to the finished tablet, such as disintegrators, colors, flavors, and sweetening agents.
One method of treating a mammal in accordance with the present invention to reduce inflamation in connective tissues includes the steps of: extracting from a first botanical sample an amount of a boswellic acid, the first botanical sample being at least one selected from the group consisting of genus Boswellia, Commiphora, and Bursera or closely related woody plant species of the family Burseraceae to derive a Boswellic acid extract; extracting from a second botanical sample an amount of a curcuminoid, the second botanical sample being at least one selected from the group consisting of turmeric, Curcuma xanthorrhiza (Zingiberaceae), Javan turmeric, and Curcuma zedoaria (Zingiberaceae), to derive a curcuminoid extract; blending an effective amount of the boswellic-acid-containing extract and an effective amount of the curcuminoid-containing extract to form a dose; and orally administering the dose to the mammal. It is preferred that the dose be administered at least once each day for a period of at least seven days.
The method of the present invention also optionally include the steps of: extracting from a third botanical sample a gingerol-containing extract, the third botanical sample being at least one selected from the Zingiber genus and blending the gingerol-containing extract with the dose; extracting from a fourth botanical sample a capsaicinoid-containing extract, the fourth botanical sample being at least one selected from the Capsicum genus and blending the capsaicinoid-containing extract with the dose; extracting from a fifth botanical sample a bioflavonoid-containing extract and blending the bioflavonoid-containing extract (for example, derived from quercetin) with the dose; and blending a vitamin C source with the dose.
Other preferred compositions of the present invention for treating inflamation of connective tissue in humans comprise: boswellic acid, a curcuminoid, a gingerol, a capsaicinoid, a bioflavonoid, and vitamin C source, all preferably extracted from a botanical source.
Still another preferred embodiment of the invention is a composition comprising, in parts by weight, about 10 to 1800 parts of Boswellia gum extract comprising at least about 10% by weight of boswellic acids, more preferably at least about 30% by weight of boswellic acids, and most preferably at least about 50% by weight of boswellic acids, and about 50 to 400 parts of turmeric gum extract comprising at least about 30% by weight of curcuminoids, more preferably at least about 50% by weight of curcuminoids, and most preferably at least about 70% by weight of curcuminoids. Preferably, the composition further comprises about 40 to 1000 parts of ginger rhizome extract comprising at least about 1% by weight of gingerols, more preferably at least about 2% by weight of gingerols, and most preferably at least about 2.5% by weight of gingerols. Further, the composition preferably additionally comprises about 20 to 500 parts of bioflavonoids. These bioflavonoids are preferably selected from the group consisting of quercetin, isoquercetin, hesperidin, rutin, troxirutin, naringen, naringenin, limonene, chrysin, isoflavones, proanthocyanidins, anthocyanidins, ellagic acid, catechin, tannin, and mixtures thereof. Citrus bioflavonoids are especially preferred bioflavonoids. In still another embodiment of the invention the composition preferably further comprises about 20 to 500 parts of cayenne pepper and/or about 100 to 500 parts of vitamin C. In yet another embodiment of the invention, the composition preferably further comprises about 20 to 500 parts of a mineral selected from the group consisting of calcium, phosphorus, and mixtures thereof. A still further preferred embodiment of the invention is in the form of a tablet and further comprises an effective amount of an additive selected from the group consisting of diluents, binders, lubricants, disintegrators, colors, flavoring agents, and mixtures thereof. Preferred additives can be selected from the group consisting of dicalcium phosphate, microcrystalline cellulose, stearic acid, gum acacia, silica, magnesium stearate, and mixtures thereof.
As is well known, many mammals suffer pain and disability from inflamation of connective tissues, particularly the tissue which makes up joints. Rheumatic diseases, such as those that primarily involve joints and which are generally known as arthritis, and those involving other connective tissues which are generally known as connective tissue diseases, impair or cripple millions. Such diseases cause huge personal and financial drains all around the world. The present invention provides a safe and effective mode of treatment of such diseases which provides benefits not heretofore available.
Importantly, in the description which follows various preferred compositions and methods of the present invention are disclosed but the scope of the present invention is not intended to be limited to the specific examples, process steps and materials disclosed herein. As will be understood, compositions, process steps and materials can vary significantly without diverging from the claimed invention.
In accordance with particular objects of the present invention, the primary ingredients of the presently preferred compositions described herein are derived from herbs such as Boswellia, turmeric, ginger, and capsicum. Each genus, family, or species, of herb provides benefits as will be fully described herein. Importantly, use of such herbal ingredients in accordance with the present invention provides relief from inflamation, pain, and swelling while avoiding the undesirable side effects of NSAIDs. Moreover, the compositions of the present invention provide herbal bioflavonoid and vitamin ingredients providing additional benefits including reducing pain and inflamation in mammalian connective tissue, particularly joints.
The compositions of the present invention preferably comprise extracts from plants belonging to at least one of following genera: Boswellia, Commiphora, and Bursera or closely related woody plant species of the family Burseraceae, from which an effective amount of one or more Boswellic acids are derived. The compositions of the present invention also preferably comprise extracts from plants providing a source of curcuminoids, such as from Curcuma longa (a common turmeric) rhizome, or from some other standardized turmeric ingredient which provides a concentrated curcuminoid extract.
While the present invention""s use of botanical extracts provides many previously unrecognized benefits, it is necessary that the botanical extracts be properly prepared to realize the benefits of the present invention. In contrast to the techniques and procedures previously used by many in the industry when preparing compositions from botanical components, when formulating the compositions of the present invention, great care must be used to ensure that standardized dosage forms of each herb and standardized amounts of active ingredients are provided in the finished composition.
The term xe2x80x9cstandardizedxe2x80x9d as used herein is intended to refer to the process whereby the plant source and the appropriate plant parts, such as rhizome, bark, seed, and so forth, are accurately identified and processed so that amounts of active ingredients in the finished composition can be predicted and thus the physiological effect of the active ingredients also anticipated. For example, a qualified botanist can utilize biochemical markers to confirm true plant identification.
Furthermore, during standardized processing of the herbs in accordance with the present invention, the extraction process which is employed to concentrate bioactive compounds found in the plants must be carefully carried out to realize many of the benefits of the present invention. Moreover, also in accordance with the present invention, analytical techniques are preferably used to ensure that the desired active compounds are present in the botanical components, at the desired levels, in the specific herbal concentrates used to make up the finished composition.
As used herein, the term xe2x80x9ceffective amountxe2x80x9d means an amount necessary to achieve a selected result. For example, administration of an effective amount of a boswellic acid or a curcuminoid will result in the desired reduction in pain and/or inflamation. By way of further example, an effective amount of a disintegrant is an amount such that a tablet formulation of the composition disintegrates to a selected extent within a selected period of time. Such an effective amount can be readily determined without undue experimentation by a person of ordinary skill in the art.
In accordance with the present invention, the botanical extracts used in the preferred compositions of the present invention can assume many forms but preferably include one or more exudate gums or standardized gum extracts derived from an appropriate botanical source. For example, a preferred source of Boswellic acids are the trees of the genus Boswellia, the genus Commiphora, the genus Bursera, or closely related woody plant species of the family Burseraceae. Also included in the preferred compositions of the present invention are curcuminoids. One preferred botanical source for the curcuminoids is common turmeric rhizome (Curcuma longa). Other preferred sources of curcuminoids preferably include a concentrated source of curcuminoids, such as extracted from turmeric samples.
The trees of the genera Boswellia, Commiphora, Bursera, or closely related woody plant species of the family Burseraceae typically grow wild in the arid and semi-arid tropics and warm temperate zones of the world and contain high concentrations of boswellic acids and other closely related compounds. Boswellic acids influence mammalian, and particularly human, eicosanoid biosynthesis.
Eicosanoids, such as prostaglandins, are involved in the inflammation of connective tissue and the contraction/relaxation of muscles, chemotaxis (especially cells of the immune system), promotion/inhibition of platelet aggregation, inhibition of gastric acid secretion, and other physiological actions. Linoleic acid, an essential fatty acid, plays an important role in proper eicosanoid metabolism in humans.
Boswellic acid gum extracts have been reported to contain different sugars like D-galactose, D-arabinose, D-xylose and D-mannose as well as volatile oil and uronic acids. As used herein, the term xe2x80x9cBoswellic acidsxe2x80x9d is intended to include related acids such as xcex2xcex2-Boswellic acids, Acetyl-xcex2xcex2-boswellic acid, keto -xcex2xcex2-boswellic acid and any other related acid which is now known or which becomes known in the future which provides the therapeutic effect described herein.
Turmeric (also spelled tumeric and also sometimes referred to as Curcumin, Curcuma longa, Indian saffron, Saffron, Curcuminoids), a member of the ginger family, contains a variety of bioactive substances called curcuminoids. The most active component is curcumin, an orange-yellow volatile oil that includes three curcuminoids: turmerone, atlantone, and zingiberone. Curcuminoids are naturally occurring phytochemicals that have beneficial effects on human eicosanoid biosynthesis leading to a net decrease in the localized production of certain inflammatory eicosanoids at the site of disease or trauma. Although curcuminoids are found in high concentrations in turmeric root, they are also present in other related plant species, such as Curcuma xanthorrhiza (Zingiberaceae) or Javan turmeric, and Curcuma zedoaria (Zingiberaceae), also known to practitioners of Chinese medicine as Shoti or Zedoary, which can readily substitute for common Indian turmeric.
In addition to boswellic acids and curcuminoids, the compositions of the present invention optionally include, in a herbaceous blend, ginger (preferably Zingiber officinalis), a rich source of gingerols. Ginger contains many active ingredients, including phenylalkylketones (gingerols, shogaols, and zingerone) and volatile oils (zingiberone, bisabolene, camphene, geraniol, linalool, and borneol). Ginger provides benefits when treating indigestion and flatulence, and it has a broad range of action against intestinal parasites. Gingerols and other active ingredients in ginger provide beneficial anti-inflammatory properties and reductions in blood platelet clumping. Gingerols are compounds that also inhibit 5-lipoxygenase in humans, and therefore reduce biosynthesis of certain inflammatory thromboxanes. See Kiuchi F., Iwakami S., Shibuya M., Hanaoka F., Sankawa U., Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids, Chem. Pharm. Bull. (Tokyo) 1992 February;40(2):387-391. The ginger is preferably provided in the form of ginger rhizome extract.
The compositions of the present invention also optionally include cayenne pepper (Capsicum annuum). Cayenne pepper is a source of capsaicinoids. Capsaicinoids are vanilyl fatty acid amides that provide the characteristic xe2x80x9chotxe2x80x9d and spicy pungency to foods containing certain peppers and capsaicin acts specifically at the site of inflammation by depleting stores of substance P from sensory neurons therefore blocking the transmission of painful stimuli to the brain. See Garrett N. E., Cruwys S. C., Kidd B. L., Tomlinson D. R., Effect of capsaicin on substance P and nerve growth factor in adjuvant arthritic rats, Neurosci Lett Jul. 11, 1997; 230(1):58.
It is believed that the mechanism responsible for the beneficial effects of some of the ingredients described herein is the reduction of pain and inflammation by interference with the development of an exaggerated inflammatory response mediated by the activity of several enzymes catalyzing the synthesis of prostaglandins and leukotrienes and the inhibition of platelet aggregation.
It is also believed that inhibition of 5-lipoxygenase and C3-convertase is thought to play the key role in the reduction in pain and inflammation observed with use of certain plant medicines containing boswellic acids, curcuminoids, capsicum and gingerols. See Ammon H. P., Safayhi H., Mack T., Sabieraj J., xe2x80x9cMechanism of antiinflammatory actions of curcumine and boswellic acids,xe2x80x9d J. Ethnopharmacol 1993 March;38(2-3):113-11 9, Department of Pharmacology, Eberhard-Karls University, Tubingen, FRG; Safayhi H., Mack T., Sabieraj J., Anazodo M. I., Subramanian L. R., Ammon H. P., xe2x80x9cBoswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase,xe2x80x9d J Pharmacol Exp Ther 1992 June;261(3):1143-11 46, Department of Pharmacology, University of Tuebingen, FRG.
On the other hand, in accordance with the present invention, Boswellia serrata extracts appear to have little or no influence on cycleoxygenase activity and are used in accordance with the present invention as alternative anti-inflammatory agents for use where NSAIDs may otherwise be contraindicated in a patient for the treatment of numerous ailments, e.g., symptomatic treatment of rheumatoid arthritis, osteoarthritis, juvenile rheumatoid arthritis, soft tissue rheumatism, gout, low back pain, myositis and fibrositis. Some of the most significant beneficial effects of Boswellia serrata on inflammation may include reduction of joint swelling, restoration and improvement of blood supply to inflamed joints, pain relief, increased mobility, reduced morning stiffness, steroid sparing, reduced disability and general improvement in quality of life and in performance of the routine activities of daily living. See Kulkami R. R., Patki P. S., Jog V. P., Gandage S. G., Patwardhan B., xe2x80x9cTreatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study,xe2x80x9d J Ethnopharmacol 1991 May;33(1-2):91-95.
Curcumin, a phytochemical component of turmeric, is known to inhibit human platelet aggregation induced by arachidonic acid, adrenaline and collagen. In vitro, it inhibits thromboxane B2 production from arachidonic acid and increases formation of 12-lipoxygenase products. Curcumin also inhibits incorporation of carbon into platelet phospholipids and inhibits the deacylation of phospholipids on stimulation with calcium. Curcumin""s anti-inflammatory properties in vivo are believed to be related to its effects on eicosanoid biosynthesis in humans.
Ginger provides additional antiinflammatory benefits. The anti-inflammatory effects of ginger are reportedly attributable to the presence of gingerols. It is also reported that the active components of ginger inhibit cyclo-oxygenase and 5-lipoxygenase activity in a manner that inhibits biosynthesis of prostaglandin E2 (PGE-2) and leukotriene B4 (LTB4), respectively. See Srivastava K. C., Mustafa T., Med Hypotheses 1992, xe2x80x9cGinger (Zingiber officinale) in rheumatism and musculoskeletal disorders,xe2x80x9d December;39(4):342-348, Department of Environmental Medicine, Odense University, Denmark. The inhibitory effects of the active components of ginger on cyclo-oxygenase activity, a key enzyme system required for biosynthesis of prostaglandins, which are active in the etiology of acute and chronic inflammation as well as cytoprotection of the gastric mucosa, is expected to be confirmed in the future. Anti-platelet activity and inhibition of thromboxane synthetase (5-lipoxygenase) are the most likely mechanisms proposed to explain the observed biological activity of ginger as an antiinflammatory agent. See Guh J. H., Ko F. N., Jong T. T., Teng C. M., xe2x80x9cAntiplatelet effect of gingerol isolated from Zingiber officinale,xe2x80x9d J Pharm Pharmacol 1995 April;47(4):329-332; Kiuchi F., Iwakami S., Shibuya M., Hanaoka F., Sankawa U., xe2x80x9cInhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids,xe2x80x9d Chem Pharm Bull (Tokyo)1992 February;40(2):387-391.
A potential advantage of Boswellia serrata, ginger and turmeric, alone or in combination, as well as the other botanical extracts described herein, is low gastrotoxicity compared to now available NSAIDs and other drug therapies. NSAIDs are contraindicated among patients who have a history of gastric ulcers or other chronic gastric conditions. NSAID use also increases the risk of developing new gastric ulcers among those who have had no history of ulcer disease. The present invention thus provides the great advantage of providing an alternative agent which can be used for relief of pain and inflammation which does not increase the risk of developing new gastric ulcers or exacerbate existing conditions in patients requiring medication for chronic pain.
It is recognized in the art that development of selective NSAIDs, which inhibit 5-lipoxygenase without also inhibiting cyclo-oxygenase, would be a great advance. Thus, the embodiments of the present invention, which provide a natural, botanical-based composition with appropriate antiinflammatory properties, fulfill a long felt need in the industry. Moreover, the embodiments of the present invention provide the unexpected safety benefits of a selective, natural 5-lipoxygenase inhibiting composition providing further advantages when treating arthritis and other inflammatory conditions.
Another optional component included in the compositions of the present invention is quercetin. Quercetin is a bioflavonoid and a natural reverse transcriptase blocker commonly found in red apples and red onions. Quercetin has been shown to have antiviral activity against HIV, herpes simplex, and the respiratory syncytial virus. Kaul, T. N., Middleton E., and Ogra P. L. xe2x80x9cAntiviral effects of flavonoids on human viruses,xe2x80x9d J Med Virol, 15: 71-79, 1985 and Vrijsen, R., Everaert, L., and Boeye A. xe2x80x9cAntiviral activity of flavones and potentiation by ascorbate,xe2x80x9d J Gen Virol 69: 1749-51, 1988.
Flavonoids (also called bioflavonoids) are natural botanical pigments that provide protection from free-radical damage, among other functions. Bioflavonoids provide protection from damaging free radicals and are believed to reduce the risk of cancer and heart disease, decrease allergy and arthritis symptoms, promote vitamin C activity, improve the strength of blood vessels, block the progression of cataracts and macular degeneration, treat menopausal hot flashes, and other ailments. Flavonoids occur in most fruits and vegetables. It is believed that flavonoids act by inhibiting hormones, such as estrogen, that may trigger hormone-dependent malignancies like cancers of the breast, endometrium, ovary, and prostate.
Limonene, a flavonoid available in citrus fruits, promotes the production of enzymes that help destroy possible carcinogens (cancer-causing agents). In addition, studies show that quercetinxe2x80x94another flavonoid found in citrus fruitsxe2x80x94can block the spread of cancer cells in the stomach. Flavonoids also stabilize mast cells, a type of immune cell that releases inflammatory compounds, like histamine, when facing foreign microorganisms. Histamine and other inflammatory substances are involved in allergic reactions. Mast cells are large cells present in connective tissue. Flavonoids fortify and repair connective tissue by promoting the synthesis of collagen. Collagen is a remarkably strong protein of the connective tissue that xe2x80x9cgluesxe2x80x9d the cells together. Flavonoids are believed to benefit connective tissue and reduce inflammation.
Citrus bioflavonoids include isoquercetin, quercetin, hesperidin, rutin, naringen, naringenin, and limonene. Isoquercetin is a common flavonoid found in onions, apples, Arnica species, Gossypium arboreum, Ginko biloba, Ricinus communis, Ocimum basilicum, Salix acutifolia, and Narcissus pseudonarcissus. Rich dietary sources of quercetin are onions, apples, kale, sweet cherries, grapes, red cabbage, and green beans. Hesperidin is found in the rinds of oranges and lemons. It helps strengthen capillary walls in conjunction with vitamin C. Naringen is found in grapefruit and is responsible for most of grapefruit""s bitter taste. Other bioflavonoids include: isoflavones, proanthocyanidins, anthocyanidins, ellagic acid, catechin, and tannin.
Isoquercetin shares the same aglycone with rutin and quercitrin: quercetin. It has been shown that quercetin-containing glycosides liberate quercetin in the intestinal tract. Therefore, it is justified to assume that all the pharmacological properties of quercetin are also shared by isoquercetin and rutin when administered orally. Recent investigation demonstrated a rapid absorption of isoquercetin and quercetin-glucosides by the sodium-dependent glucose transport pathway in the small intestine. Due to superior bioavailability, the health effects of isoquercetin are increased compared to other flavonoids. Isoquercetin is known to have anti-inflammatory activity without adverse effects on the gastrointestinal tract, such as those caused by NSAIDs. Isoquercetin further exhibits beneficial effects as an antioxidant, antihypertensive, anticarcinogenic, antimicrobial, and analgesic agent.
Other bioflavonoids that can be added advantageously to the compositions of the present invention include troxirutin, and chrysin, which contains analgesic properties related to benzodiazepine receptor agonism.
The benefits of vitamin C are well known. In accordance with the present invention, a vitamin C source can preferably include those vitamin C sources known in the industry and particularly those selected from the group consisting of ascorbic acid, ascorbyl palmitate, and mineral ascorbates.
Isoflavones which are found in soy foods such as soybeans, tofu, tempeh, soy milk, textured vegetable protein, soy flour, and miso. Two significant isoflavones are genistein and daidzein.
Proanthocyanidins that are bound together are collectively called proanthocyanidin oligomers, or PCOs. PCOs are plentiful in grape seeds, red wine, and extracts of the bark of the maritime pine.
Anthocyanidins are plant pigments responsible for the red- to blue-red colors in blackberries, raspberries, blueberries, and cherries. When consumed, anthocyanidins attach to connective tissue, where they strengthen collagen.
Ellagic acid, a flavonoid in fruits (especially grapes) and vegetables, appears to directly protect genes from toxic compounds.
It is also within the scope of the present invention to add certain minerals to the compositions described herein. Many people, particularly those people living in North America, do not currently consume enough calcium. Calcium is important in the maintenance of bones and teeth, where it is primarily found with phosphorus as hydroxyapatite. Calcium also plays extremely important roles in cell communication and the regulation of body processes. Calcium also helps regulate enzymes and is necessary in blood clotting. It is involved in transmitting chemical and electrical signals along nerves and muscles, and is necessary for the release of neurotransmitters, which allow nerve impulses to pass from one nerve to another and from nerves to tissues. Calcium also plays a role in blood pressure regulation, possibly by controlling the contraction of muscles in the blood vessel walls and signaling the secretion of substances that regulate blood pressure. Inside muscle cells, calcium allows two muscle proteins, actin and myosin, to interact to cause muscle contraction. It is not possible to precisely estimate the dietary intake needed for maximum retention of calcium, thus, rather than a recommended dietary allowance (RDA), an adequate intake (AI) for adults age 19 through 50 years of 1000 mg per day has been determined. Since calcium absorption decreases with age, the AI for older adults is 1200 mg per day. For adolescents the AI is higher than for adults-1300 mg per day for boys and girls age 9 through 18.
Phosphorus makes up about 1% of the adult body by weight, and 85% or this is found as a structural component of bones. Phosphorus is also a component of phospholipids, which form the structure of cell membranes. Phosphorus is also a major constituent of DNA and RNA. Phosphorus is also involved in regulating enzyme activity because addition of a phosphate group can activate or deactivate certain enzymes. The high-energy bonds of ATP are formed between phosphate groups. Phosphorus as phosphate is an important buffer that helps regulate the pH in the cytoplasm of all cells. For adults 19 to 50 years of age, the RDA for phosphorus is 700 mg.
As described previously, the compositions of the present invention may be manufactured in tablet, liquid, or powder form. In powder form, the various dry, powdered ingredients are mixed together until a relatively homogeneous mixture is obtained. The powder is generally administered by mixing with a liquid, such as water or fruit juice, and then drinking the resulting suspension. In liquid form, the powder is mixed with an appropriate liquid carrier, preferably water, and the resulting suspension is packaged in appropriate containers. In tablet form, the ingredients are mixed together and then the tablets prepared according to methods well known in the art: (1) the wet-granulation method, (2) the dry-granulation method, or (3) direct compression. See Remington""s Pharmaceutical Sciences.
As used herein, xe2x80x9ctabletsxe2x80x9d are solid dosage forms containing the active substances with or without suitable additives and prepared either by compression or molding methods well known in the art. See Remington""s Pharmaceutical Sciences. Tablets are a preferred dosage form because of the advantages afforded both to the manufacturer (e.g., simplicity and economy of preparation, stability, and convenience in packaging, shipping, and dispensing) and the user (e.g., accuracy of dosage, compactness, portability, blandness of taste, and ease of administration). Although tablets are most frequently discoid in shape, they may also be round, oval, oblong, cylindrical, or triangular. They may differ greatly in size and weight depending on the amounts of active substances present and the intended method of administration. They are divided into two general classes, (1) compressed tablets, and (2) molded tablets or tablet triturates. In addition to the active ingredients, tablets contain a number or inert materials or additives. A first group of such additives includes those materials that help to impart satisfactory compression characteristics to the formulation, including diluents, binders, and lubricants. A second group of such additives helps to give additional desirable physical characteristics to the finished tablet, such as disintegrators, colors, and flavoring agents.
As used herein, xe2x80x9cdiluentsxe2x80x9d are inert substances added to increase the bulk of the formulation to make the tablet a practical size for compression. Commonly used diluents include calcium phosphate, calcium sulfate, lactose, kaolin, mannitol, sodium chloride, dry starch, powdered sugar, and the like.
As used herein, xe2x80x9cbindersxe2x80x9d are agents used to impart cohesive qualities to the powdered material. Binders, or xe2x80x9c granulatorsxe2x80x9d as they are sometimes known, impart a cohesiveness to the tablet formulation, which insures the tablet remaining intact after compression, as well as improving the free-flowing qualities by the formulation of granules of desired hardness and size. Materials commonly used as binders include starch; gelatin; sugars, such as sucrose, glucose, dextrose, molasses, and lactose; natural and synthetic gums, such as gum acacia, sodium alginate, extract of Irish moss, panwar gum, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone, Veegum, microcrystalline cellulose, microcrystalline dextrose, amylose, and larch arabogalactan, and the like.
As used herein, xe2x80x9clubricantsxe2x80x9d are materials that perform a number of functions in tablet manufacture, such as improving the rate of flow of the tablet granulation, preventing adhesion of the tablet material to the surface of the dies and punches, reducing interparticle friction, and facilitating the ejection of the tablets from the die cavity. Commonly used lubricants include talc, magnesium stearate, calcium stearate, stearic acid, and hydrogenated vegetable oils. Preferred amounts of lubricants range from about 0.1% by weight to about 5% by weight.
As used herein, xe2x80x9cdisintegratorsxe2x80x9d or xe2x80x9cdisintegrantsxe2x80x9d are substances that facilitate the breakup or disintegration of tablets after administration. Materials serving as disintegrants have been chemically classified as starches, clays, celluloses, algins, or gums. Other disintegrators include Veegum HV, methylcellulose, agar, bentonite, cellulose and wood products, natural sponge, cation-exchange resins, alginic acid, guar gum, citrus pulp, cross-linked polyvinylpyrrolidone, carboxymethylcellulose, and the like.
As used herein, xe2x80x9ccoloring agentsxe2x80x9d are agents that give tablets a more pleasing appearance, and in addition help the manufacturer to control the product during its preparation and help the user to identify the product. Any of the approved certified water-soluble FDandC dyes, mixtures thereof, or their corresponding lakes may be used to color tablets. A color lake is the combination by adsorption of a water-soluble dye to a hydrous oxide of a heavy metal, resulting in an insoluble form of the dye.
As used herein, xe2x80x9cflavoring agentsxe2x80x9d are compounds designed to give the tablet a more palatable taste. Flavoring agents vary considerably in their chemical structure, ranging from simple esters, alcohols, and aldehydes to carbohydrates and complex volatile oils. Synthetic flavors of almost any desired type are now available and are well known in the art.
The following examples provide illustrative representations of the effectiveness of some preferred compositions within the scope of the present invention. The following examples are not intended to limit the scope of the claims set forth herein.

Composition and method for treatment of inflammation and pain in mammals


An apparatus for modulating an incident beam includes a body that is non-transmissive and rotatable about an axis perpendicular to a surface of the body. The body has a first set of features including transmissive features with respect to the incident beam along a first radial path at a first radial distance from the axis and a second set of features including data storage features along a second radial path at a second radial distance from the axis. The apparatus also includes a reference sensor disposed over a first position along the second radial path. In the apparatus. the radial distances are different and the numbers of transmissive features and data storage features are relatively prime. When the body is rotating, the first set of features modulate the incident beam and the reference sensor generates a reference signal based on the data storage features traversing the first position.

In general, a measurement result typically includes some portion or contribution attributable to the desired signal of interest, and some portion attributable to noise, jitter, and/or interference. Based on the magnitude of the signal of interest relative to the magnitude of noise, jitter, and/or interference, the sensitivity and accuracy of the measurement are limited. The measurand generally cannot be measured accurately if the signal-to-noise ratio (SNR) or signal-to-noise-plus-interference ratio (SNIR) is less than one. However, special techniques can be used to limit the effective bandwidth of the measurement process to regions where the signal is high and noise is low, thereby effectively increasing the signal-to-noise ratio and increasing the ability to extract the true value of the measurand from the noisy measurement result. For example, simple averaging can be used to increase the effective signal-to-noise ratio in some cases, especially in the case of white noise. Unfortunately, in many cases, the dominant noise is not white noise and simple averaging may not be effective. Therefore, more sophisticated techniques are generally needed to recover the signal.
A lock-in amplifier is commonly used to measure or extract the amplitude and phase of the measurand in a modulated signal that is accompanied by a significant amount of noise and/or interference. In general, lock-in amplifiers require modulated signals, and such modulation may be achieved by using a chopped incident beam. A lock-in amplifier makes use of a priori information describing the modulation of the signal, in the form of an internal reference signal or waveform corresponding to the modulation waveform of the signal, to recover or extract the signal from the noise. A lock-in amplifier mixes (multiplies point-by-point) the measured input signal with the internal reference signal waveform, and integrates the result of this process over a specified time interval, which can be chosen according to the signal and noise characteristics present in the system, the desired accuracy and precision of the measurement, and the time allowed for the measurement. The result of the integration may be seen as an essentially-DC signal which corresponds to the amplitude of the original signal before modulation. Contributions from any source of noise, interference, or perturbation that are not at the same frequency and/or phase as the internal reference signal are effectively cancelled, as the integrated result of the mixing process from these contributions will approach or tend toward a zero value. Offset or baseline errors in the signal measurement channel will also be eliminated, because the reference waveform has an average value of zero. Importantly, chopping and lock-in amplification allow for the reduction of 1/f noise which dominates many experimental systems at lower frequencies. By modulating the signal, the experimental system can be effectively removed from the region where 1/f noise sources dominate.

Signal measurement apparatus and beam modulation apparatus used therein


A method and apparatus for limiting longitudinal stretch during fixation of a harvested aortic root including valve leaflets and the product produced. The apparatus includes an inflow plug inserted into the inflow section of the aortic root and having an apertured tube or cannula extending through the valve leaflets to an outflow plug inserted into the outflow section of the aortic root. Apertures in the tube are located on either side of the valve leaflets and the tube is coupled to a fluid inlet, preferably located on the outflow plug. The outflow plug is slidable relative to the tube and is provided with an engagement mechanism such as a setscrew for fixing the location of the outflow plug relative to the tube and the inflow plug. After assembly of the aortic root to the apparatus, the fluid inlet is coupled to a source of defined pressure and the root is inflated. The outflow plug is then fixed relative to the tube to define the maximum elongation of the root and fixative is then delivered to the interior of the root via the apertured tube.

The present invention relates to the production of tissue heart valves generally and more particularly to fixtures for use in conjunction with fixation of valve tissue.
Tissue heart valves may be fabricated by harvesting a mammalian aortic root including the aortic valve and thereafter fixing the harvested aortic root to crosslink the tissue. Thereafter, the aortic root may be trimmed and employed as heart valve for implantation in human beings. The valve may be mounted to a stent or frame, for example as disclosed in U.S. Pat. No. 5,824,069, issued to Lemole, U.S. Pat. No. 4,816,029, issued to Penney, et al., U.S. Pat. No. 5,716,401, issued to Eberhardt, et al. or U.S. Pat. No. RE 30,912, issued to Hancock. Alternatively, the valve may be implanted without an associated stent, as described in U.S. Pat. No. 5,336,258, issued to Quintero, et al or U.S. Pat. No. 6,074,419, issued to Healy, et al.
U.S. Pat. No. 5,824,060 issued to Christie, et al. and incorporated herein by reference in its entirety describes a process for heart valve fixation, in which the harvested aortic root is subjected to a fixative fluid to provide a first differential fluid pressure across the tubular wall of the outflow section of the aortic root and a second differential fluid pressure across the valve leaflets. As disclosed, the inflow and outflow sections of the aortic root are coupled to fluid couplings that are in turn coupled to sources of fixative fluid under pressure. The entire assembly is also placed in fixative fluid during the fixation process.
U.S. Pat. No. 5,830,239 issued to Toomes and incorporated herein by reference in its entirety describes an improvement to the process of the ""060 patent, in which only the outflow section of the aortic root is mounted to a fluid coupling and the inflow section of the root is blocked by a plug. The plug is provided with a tube or cannula having an inlet portion extending through the valve leaflets and an outlet opening located in the inflow section of the aortic root, allowing fixative fluid to flow through the valve so that fluid may be applied to both sides of the valve and to the inflow and outflow sections of the aortic root. The fluid coupling is coupled to a source of fixative and the entire assembly is placed in fixative during the fixation process. The process disclosed in the ""239 patent substantially simplifies the fixturing process as compared to the ""060 patent.
The present invention is an improvement to the process described in the ""239 patent, providing a way to control axial stretch of the aortic root during the fixation process. Because the stretch of the aortic root is controlled, the fixturing system and process of the present invention is intended to produce an increased yield as compared to the process in the ""239 patent.
The fixturing system of the present invention resembles that as described in the ""239 patent, in that only a single fluid coupling is employed, preferably part of an outflow plug coupled to the outflow section of the aortic root, and in that the inflow section of the aortic root is blocked by an inflow plug. However, in the present invention, the cannula or tube extending from the inflow plug extends through the valve all the way to the outflow plug. The tube smoothly slides into the outflow plug, allowing for adjustment of the relative positions of the inflow and outflow plug. The outflow plug preferably has a setscrew or other mechanism associated therewith for fixing the location of the inflow plug relative to the outflow plug. The tube is provided with a series of holes extending along of the tube and arranged to be located on both sides of the valve leaflets, so that a zero pressure differential across the leaflets can be achieved during fixation.
In use, the outflow section of the aortic root is preferably first coupled to the fluid coupling, which in the preferred embodiment of the invention is part of an outflow plug, around which the outflow section of the aortic root is mounted. The fluid coupling is then coupled to a source of compressed air to close the valve leaflets and a contour ring is placed around the inflow section of the aortic root. The aortic tissue at the end of the inflow section of the aortic root is then folded back over the contour ring and a length of plastic tubing is slid over the tissue and contour ring and is maintained in place, for example, by means of a cable tie. Other mechanisms for restraining the outflow section of the aortic root during fixation may be substituted for the contour ring or the contour ring might, in some embodiments, be attached without prior application of pressure to close the valve leaflets.
The apertured tube or cannula and the attached inflow plug are then inserted into the aortic root with the tube passing through the valve leaflets and engaging the fluid coupling. The inflow plug attached to the tube is located within the plastic tubing and attached to it by means of cable ties or the like, compressing the tubing around the inflow plug. The fluid coupling is then again attached to a source of compressed air, which is used to inflate the aortic root to a desired pressure and the setscrew is employed to fix the outflow plug to the tube, correspondingly stabilizing the relative location of the inflow and outflow sections of the aortic root and preventing excessive longitudinal stressing during fixation. The assembly is then moved to a fixative bath where the outflow plug is coupled to a source of fixative under pressure, and the assembly is placed into the fixative bath during the fixation process. On completion of fixation, the aortic root is removed and trimmed and may thereafter be mounted to an associated heart valve stent.

Heart valve fixation process and apparatus


A lithographic printing plate precursor comprises an electrochemically grained aluminium substrate, the grained surface of which is coated with a layer of gel-like amorphous colloidal oxides and hydroxides of aluminium and their hydrates incorporating metallic aluminium and inter-metallic aluminium alloysxe2x80x94generally at a level of below 5%xe2x80x94this layer being produced during the electrochemical graining process. The layer is typically present in an amount of from 0.1-20 g/m2 and at a layer thickness of 0.1-4.0 xcexcm, the particle sizes in the said layer generally falling in the range of from 10 to 2000 nm. Methods are disclosed for the preparation of said precursors via the electrochemical graining of aluminium substrates. The invention provides lithographic printing plate precursors which may be imagewise exposed by means of a high intensity laser beam to provide printing plates showing high durability on press and giving images which show good resolution and are free from background staining.

This invention relates to the formation of images directly from electronically composed digital sources and is particularly concerned with the formation of images on lithographic printing plate precursors. More particularly, the invention relates to lithographic printing plate precursors which incorporate an imaging layer comprising gel-like amorphous colloidal oxides and hydroxides of aluminium and their hydrates incorporating metallic aluminium and inter-metallic aluminium alloys, and a method of preparing lithographic printing plates wherein image formation is achieved by means of exposure to thermal radiation, and which does not require the use of chemical treatments.
Lithographic printing is a process of printing from surfaces which have been prepared in such a way that certain areas are capable of accepting ink (oleophilic areas), whereas other areas will not accept ink (oleophobic areas). The oleophilic areas form the printing areas while the oleophobic areas form the background areas.
Plates for use in lithographic printing processes may be prepared using a photographic material that is made imagewise receptive or repellent to ink upon photo-exposure of the photographic material and subsequent chemical treatment. However, this method of preparation, which is based on photographic processing techniques, involves several steps, and therefore requires a considerable amount of time, effort and expense.
Consequently it has, for many years, been a long term aim in the printing industry to form images directly from an electronically composed digital database, ie by a so-called xe2x80x9ccomputer-to-platexe2x80x9d system. The advantages of such a system over the traditional methods of making printing plates are:
(i) the elimination of costly intermediate silver film and processing chemicals;
(ii) a saving of time; and
(iii) the ability to automate the system with consequent reduction in labour costs.
The introduction of laser technology provided the first opportunity to form an image directly on a printing plate precursor by scanning a laser beam across the surface of the precursor and modulating the beam so as to effectively turn it on and off. In this way, radiation sensitive plates comprising a high sensitivity polymer coating have been exposed to laser beams produced by water cooled UV argon-ion lasers and electrophotographic plates having sensitivities stretching into the visible spectral region have been successfully exposed using low powered air-cooled argon-ion, helium-neon and semiconductor laser devices.
Imaging systems are also available which involve a sandwich structure which, on exposure to a heat generating infra-red laser beam, undergoes selective (imagewise) delamination and subsequent transfer of materials. Such so-called peel-apart systems are generally used as replacements for silver halide films.
A digital imaging technique has been described in U.S. Pat. No. 4,911,075 whereby a so-called driographic plate which does not require dampening with an aqueous fountain solution to wet the non-image areas during printing is produced by means of a spark discharge. In this case, a plate precursor comprising an ink-repellent coating containing electrically conductive particles coated on a conductive substrate is used and the coating is ablatively removed from the substrate. Unfortunately, however, the ablative spark discharge provides images having relatively poor resolution.
It is known to improve this feature by the use of lasers to obtain high resolution ablation as described, for example, by P E Dyer in xe2x80x9cLaser Ablation of Polymersxe2x80x9d (Chapter 14 of xe2x80x9cPhotochemical Processing of Electronic Materialsxe2x80x9d, Academic Press, 1992, p359-385). Until recently, imaging via this method generally involved the use of high power carbon dioxide or excimer lasers. Unfortunately, such lasers are not well-suited to printing applications because of their high power consumption and excessive cost, and the requirement for high pressure gas handling systems. Recent developments have, however, led to the availability of more suitable infra-red diode lasers, which are compact, highly efficient and very economical solid state devices. High power versions of such lasers, which are capable of delivering up to 3000 mJ/cm2, are now commercially available.
Coatings which may be imaged by means of ablation with infra-red radiation have previously been proposed. Thus, for example, a proofing film in which an image is formed by imagewise ablation of a coloured layer on to a receiver sheet is described in PCT Application No. 90/12342. This system is, however, disadvantageous in requiring a physical transfer of material in the imaging step, and such methods tend to give rise to inferior image resolution.
Much superior resolution is obtained by means of the ablation technique described in European Patent No 649374, wherein a driographic printing plate precursor is imaged digitally by means of an infra-red diode laser or a YAG laser, and the image is formed directly through the elimination of unwanted material. The technique involves exposing a plate precursor, incorporating an infra-red radiation ablatable coating covered with a transparent cover sheet, by directing the beam from an infra-red laser at sequential areas of the coating so that the coating ablates and loses its ink repellancy in those areas to form an image, removing the cover sheet and ablation products, and inking the image.
A heat mode recording material is disclosed in U.S. Pat. No. 4,034,183 which comprises an anodised aluminium support coated with a hydrophilic layer. On imagewise exposure using a laser, the exposed areas are rendered hydrophobic, and thereby accept ink.
Japanese patent application laid open to public inspection No 49-117102 (1974) discloses a method for producing printing plates wherein a metal is incorporated in the imaging layer of a printing plate precursor which is imaged by irradiation with a laser beam modulated by electric signals. Typically, the plate precursor comprises a metal base, such as aluminium, coated with a resin film, which is typically nitrocellulose, and on top of which has been provided a thin layer of copper. The resin and metal layers are removed in the laser-struck areas, thereby producing a printing plate. The disadvantage of this system, however, is that two types of laser beam irradiation are required in order to remove firstly the copper (eg by means of an argon-ion laser) and then the resin (eg with a carbon dioxide laser); hence, the necessary equipment is expensive.
Subsequently a method of printing plate production which obviated the requirement for a second laser exposure was disclosed in Japanese patent application laid open to public inspection No 52-37104 (1977). Thus, a printing plate precursor comprising a support, typically aluminium, an anodic aluminium oxide layer, and a layer of brass, silver, graphite or, preferably, copper is exposed to a laser beam of high energy density in order to render the exposed areas hydrophilic to yield a printing plate. The printing plate precursor is, however, of rather low sensitivity and requires the use of a high energy laser for exposure.
An alternative heat mode recording material for making a lithographic printing plate is disclosed in European Patent No 609941, which comprises a support having a hydrophilic surface, or provided with a hydrophilic layer, on which is coated a metallic layer, on top of which is a hydrophobic layer having a thickness of less than 50 nm. A lithographic printing plate may be produced from the said material by imagewise exposing to actinic radiation, thereby rendering the exposed areas hydrophilic and repellent to greasy ink.
Conversely, European Patent No 628409 discloses a heat mode recording material for making a lithographic printing plate which comprises a support and a metallic layer, on top of which is provided a hydrophilic layer having a thickness of less than 50 nm. A lithographic printing plate is produced by imagewise exposing the material to actinic radiation in order to render the exposed areas hydrophobic and receptive to greasy ink.
In each of the two foregoing heat mode recording materials, however, difficulties in printing will be encountered. On exposure of the materials to actinic radiation, the energy is converted to heat in the image areas by interaction with the metallic layer, thereby destroying the hydrophilicity or hydrophobicityxe2x80x94depending on the material employedxe2x80x94of the topmost layer in those areas. Consequently, the surface of the metallic layer becomes exposed, and the success of the printing operation is dependent upon differences in hydrophilicity and oleophilicity between the metallic surface and the hydrophilic or hydrophobic layer, as the case may be. Since the metallic layer functions as the hydrophobic surface in one case, and as the hydrophilic surface in the alternative case, it would be expected that such differences in hydrophilicity and oleophilicity would not be sufficiently clearly defined so as to provide a satisfactory printing surface. Furthermore, when a hydrophilic layer is present, and the metallic surface functions as the oleophilic areas of the plate, image areas will necessarily be printed from the metallic surface; such an arrangement is known to be unsatisfactory, and to result in difficulties in achieving acceptable printing quality.
Subsequently, imaging systems have been provided wherein a radiation sensitive layer comprising metallic silver is applied to a grained and anodised aluminium substrate, the resulting lithographic printing plates being imaged by exposure to thermal radiation which causes ablation of the silver layer in the radiation struck areas. The resulting systems, which are described in PCT patent applications WO 98/55307-WO 98/55311 and WO 98/55330-WO 98/55332 provide press ready plates showing high image quality, good press properties and high durability on press without the requirement for the use of costly intermediate film and developer chemistry and the attendant inconvenience resulting from the use of these materials. However, the plates do utilise costly silver intermediates in their manufacture and, as a consequence, are expensive to use. Indeed, in all of the systems of the prior art, it is necessary that a costly radiation sensitive layer should be applied to a prepared substrate in order to provide an imaging system.
Consequently, it is an object of the present invention to provide an imaging system which obviates the requirement for the use of costly radiation sensitive imaging layers.
It is a further object of the present invention to provide a lithographic printing plate having excellent printing properties, and a method of making said plate which obviates the requirement for the use of processing developers after exposure.
It is a still further object of the present invention to provide a method of preparing a lithographic printing plate which does not require the use of costly intermediate film and relies on direct-to-plate exposure techniques.
It is also an object of the present invention to provide a method of producing a lithographic printing plate in which a high quality image results from the ablation of a layer from a hydrophilic support, thus providing a high degree of differentiation between hydrophilic and oleophilic areas.
The present invention provides in one aspect a method for making a lithographic printing plate. The method comprises the steps of providing a lithographic printing plate precursor comprising an electrochemically grained aluminium substrate, the grained surface of which is coated with a smut layer comprising amorphous colloidal oxides and hydroxides of aluminium and their hydrates incorporating metallic aluminium and inter-metallic aluminium alloys, and exposing the lithographic printing plate precursor to heat, wherein the smut layer is removed from the substrate by ablation.
According to a first aspect of the present invention there is provided a lithographic printing plate precursor comprising an electrochemically grained aluminium substrate, the grained surface of which is coated with a layer of gel-like amorphous colloidal oxides and hydroxides of aluminium and their hydrates incorporating metallic aluminium and inter-metallic aluminium alloys, the said layer being produced during the electrochemical graining process.
Said layer of gel-like amorphous colloidal oxides and hydroxides of aluminium and their hydrates incorporating metallic aluminium and inter-metallic aluminium alloys is commonly referred to as a xe2x80x98smutxe2x80x99 layer, and said inter-metallic aluminium alloys comprise alloys of aluminium with the other metals generally present in lithographic quality aluminium. Said metals primarily include manganese and iron, which may be present in amounts of between 0.5 and 1.0%, together with lesser quantities of other metals, such as magnesium, copper, zinc and titanium. In any event, the overall level of metallic aluminium and inter-metallic aluminium alloys present in the layer of amorphous colloidal oxides and hydroxides of aluminium and their hydrates rarely exceeds 5% and, in general, these materials would be present at levels below 1%.
The chemical graining process is preferably an electrochemical graining process which is carried out by passing the aluminium substrate through a bath containing at least a mineral acid, under the influence of an electric current.
Preferably, said mineral acid is hydrochloric or nitric acid, which is applied to the aluminium surface either alone or in combination with another acid, preferably an organic acid such as acetic acid. Said organic acid is advantageously present at a level of 0-80%, preferably 0-10%, most preferably 0-5%. Especially effective results are obtained with a mixture of hydrochloric and acetic acids in the ratio of 2:1 to 1:4, preferably 1:2. Optionally said mineral acid may also contain amounts of salts at a level of 0-80%, preferably 0-20%; suitable examples of such salts include aluminium chloride, aluminium sulphate, aluminium nitrate, ammonium chloride and potassium hexafluorozirconate.
The electric current may be a direct current or an alternating current, but is most preferably an alternating current having a current density of from 500-5000 A/m2, most particularly from 2000-3000 A/m2. The current can be applied in AC, sine or square waveforms having from 1 to 6 phases, with either positive or negative biasing, at xc2x110 V. The charge densities are from 1 to 1000 C/dm2, preferably from 200 to 1000 C/dm2. The graining process is carried out at a temperature of from 0-100xc2x0 C., preferably from 20-50xc2x0 C., for a dwell time of from 2 seconds to 3 minutes, preferably from 2 seconds to 20 seconds.
The layer of smut is preferably present in an amount of from 0.1-20 g/m2, giving a layer thickness of from 0.1-4.0 xcexcm. The particle sizes in the said layer typically range from 10 to 2000 nm, preferably from 50 to 500 nm, in diameter.
The substrate employed in the present invention is an aluminium substrate which is chemically grained on at least one surface in order to enhance its lithographic properties. Optionally, however, the aluminium may be laminated to other materials, such as paper or various plastics materials, in order to enhance its flexibility, whilst retaining the good dimensional stability associated with aluminium.
Preferably, the plate precursors according to the first aspect of the present invention additionally include an anodic layer, said layer comprising oxides of aluminium and being formed by means of an electrochemical anodising process. Said process involves treatment of the grained substrate, including the smut layer, in an acid bath, preferably comprising at least a mineral acid, in the presence of an electric current. Typically the mineral acid comprises sulphuric or phosphoric acid, or a mixture of the two acids, preferably in a ratio of from 1:10 to 1:1, most preferably in a ratio of around 1:7. The process could suitably be carried out using, for example, a total acid concentration of 8-15%, with a dwell time of from 2 seconds to 2 minutes, in a bath having a temperature of from 10xc2x0 to 50xc2x0 C. A suitable current density for the process would be in the region of 1000 A/m2.
In order that a high degree of differentiation in terms of oleophilicity and hydrophilicity should be achieved between image and non-image areas, it is required that the entire layer of smut should be ablated from the substrate, and it is preferred that the lithographic printing plate should include a top layer comprising an oleophilic material, such as a binder resin, an organic compoundxe2x80x94for example octylmercaptotetrazolexe2x80x94or a metal such as silver or copper. Preferably, said oleophilic material comprises a polymeric material such as a polyurethane, nylon, (meth)acrylate, styrene, acrylonitrile or novolak resin or copolymer, but is most preferably a carboxylated polymer obtained by reacting a proportion of the residual hydroxy groups in a poly(vinyl acetal) resin, such as poly(vinyl butyral), with an acid anhydride, for example trimellitic anhydride, maleic anhydride or, preferably, phthalic anhydride.
As an alternative, it is possible to include a top layer comprising a material having a greater degree of hydrophilicity than the smut layer; this allows areas of differential ink acceptance to be provided following exposure of the material such that partial ablation of the lower layer occurs. Particularly favourable results are achieved with a hydrophilic layer comprising titanium dioxide, silicon dioxide and poly(vinyl alcohol), and the effect may be further enhanced by treatment of the anodised substrate surface with an agent capable of increasing its degree of hydrophobicity; suitable results in this regard are achieved by the use of complex salts such as potassium hexafluorozirconate.
As a still further alternative, a so-called driographic plate may be obtained by applying a top layer comprising an oleophobic material, typically an oleophobic polymeric resin, preferably a polysiloxane. Such driographic plates are advantageous in that printing may be carried out on presses without the need for damping solutions to be employed.
Optionally, an intermediate layer may be present between said smut layer and said top layer. Said intermediate layer may include a dynamic release accelerator which increases the rate of ablation of the material of the top layer during exposure of the printing plate precursor, thereby increasing the exposure sensitivity of the precursor. Suitable dynamic release accelerators could comprise, for example, a very thin layer of silver metal, but, more generally will include polymeric materials which undergo thermal decomposition, typical examples being azide or cellulosic polymers, polysulphones, polycarbonates and methacrylate polymers, such as tertiary butyl methacrylate polymers; most preferably, however, the dynamic release accelerator comprises nitrocellulose.
A second aspect of the current invention concerns a method for the preparation of lithographic and driographic printing plate precursors as envisaged according to the first aspect of the invention, said method comprising electrochemically graining an aluminium substrate in the manner hereinbefore described.
Furthermore, according to a third aspect of the present invention, there is provided a method of preparing a lithographic printing plate, said method comprising:
a) providing a lithographic printing plate precursor as hereinbefore described;
b) imagewise exposing said precursor by means of a high intensity laser beam;
and
c) removing extraneous material from imaged areas.
In order to prepare a lithographic printing plate, the precursor is imaged by a beam of radiation, preferably from a laser operating in the infra-red region of the spectrum. Examples of suitable infra-red lasers include semiconductor lasers and YAG lasers, for example the Agfa Galileo 2 Platesetter with a 12 W YAG laser outputting at 1064nm. Exposure to the beam of radiation causes ablation of the smut layer to occur in the radiation-struck areas.
In the case wherein the precursor includes a top layer comprising an oleophilic material, it is found that the said layer is generally ablated from the plate on exposure, together with the greater part of the smut layer. Remaining parts of said smut layer may subsequently be removed by simple physical rubbing with a dry or damp cloth, or by treatment with a suitable plate cleaning solution, such as NORMAKLEEN(trademark), FORTAKLEEN(trademark)or KLEENGUM(trademark).
However, when the precursor is a driographic printing plate precursor incorporating a hydrophobic top layer, this layer is not ablatively removed on exposure, nor by physical rubbing. Consequently, treatment with a processing solution is required in order to provide a press-ready plate. Suitable treatment solutions typically include PP1 and PA1.
The lithographic printing plates obtained by the method according to the second aspect of the present invention may be used on printing presses to obtain in excess of 50,000 high quality copies showing good resolution, and free from background staining.
The following examples are illustrative of the conditions employed in the preparation of lithographic printing plate precursors according to the invention, without placing any limit on the scope thereof:

Heat sensitive printing plate precursors


An improved holder, system and method for implanting a tissue-type prosthetic heart mitral valve that constricts the commissure posts of the valve and allows the user to detach the handle of the holder prior to withdrawing the holder itself. The ability to remove the handle allows a surgeon greater access to suturing the prosthetic valve to the mitral annulus. The holder may include two relatively movable plates, one of which attaches to the valve sewing on the inflow end of the valve ring and the other which attaches via sutures to the valve commissures on the outflow end. Separation of the plates places the sutures in tension and constricts the commissures. An adjusting member or adapter is interposed between the handle and holder to enable separation of the two plates and removal of the handle. The adjusting member or adapter may be packaged with the valve and holder combination, or may be sold as a separate unit, possibly with the handle, so that prior art holders can be retrofit.

The present invention relates generally to medical devices, and more particularly to an apparatus for facilitating the implantation of a bioprosthetic replacement heart valve, and associated methodology.
In mammalian animals, the heart is a hollow muscular organ having four pumping chambers: the left and right atria and the left and right ventricles, each provided with its own one-way valve. The natural heart valves are identified as the aortic, mitral (or bicuspid), tricuspid and pulmonary valves and have leaflets to control the directional flow of blood through the heart. The valves are each mounted in an annulus that comprises a dense fibrous ring attached either directly or indirectly to the atrial or ventricular muscle fibers. Various surgical techniques may be used to repair a diseased or damaged valve. In a valve replacement operation, the damaged leaflets are excised and the annulus sculpted to receive a replacement valve.
Two primary types of heart valve replacements or prostheses are known. One is a mechanical-type heart valve that uses a ball and cage arrangement or a pivoting mechanical closure to provide unidirectional blood flow. The other is a tissue-type or xe2x80x9cbioprostheticxe2x80x9d valve which is constructed with natural-tissue valve leaflets which function much like a natural human heart valve""s, imitating the natural action of the flexible heart valve leaflets which form commissures to seal against each other to ensure the one-way blood flow. In tissue valves, a whole xenograft valve (e.g., porcine) or a plurality of xenograft leaflets (e.g., bovine pericardium) provide occluding surfaces that are mounted within a surrounding stent structure. In both types of prosthetic valves, a biocompatible cloth-covered sewing or suture ring is provided on the valve body, for the mechanical type of prosthetic valve, or on the inflow end of the stent for the tissue-type of prosthetic valve.
In placing a tissue type prosthetic valve in the mitral position, the commissure posts are on the blind side of the valve and may become entangled with pre-installed sutures, and may damage the annulus or tissue during delivery. The difficulty of the delivery task is compounded if the surgery is through a minimally-invasive access channel, a technique that is becoming more common. The problem of entanglement is termed xe2x80x9csuture looping,xe2x80x9d and means that the suture that is used to attach or mount the valve to the heart tissue is inadvertently wrapped around the inside of one or more of the commissure post tips. If this occurs, the looped suture may damage one of the tissue leaflets when tightly tied down, or at least may interfere with valve operation and prevent maximum coaptation of the valve leaflets, resulting in a deficiency in the prosthetic mitral valve.
Some attempts have been made to overcome these problems in current holders for prosthetic mitral valves. An example of such a holder is U.S. Pat. No. 4,865,600, Carpentier, et al., incorporated herein by reference. Carpentier provides a holder having a constriction mechanism that constricts the commissure posts inwardly prior to implantation. The Carpentier device provides an elongate handle to both hold the valve/valve holder combination during implantation, as well as to cause the commissure posts to constrict inwardly. The valve is connected to the valve holder by the manufacturer using one or more sutures, and the combination shipped and stored as a unit. During the valve replacement procedure, the surgeon connects the handle to the holder and locks a locking nut to hold the commissure posts at a given constricted position. The surgeon then attaches the sewing ring of the valve to the native valve annulus with an array of sutures that has been pre-embedded in the annulus and extended outside the body. The valve is then advanced along the array of sutures to its desired implantation position and the sutures tied off. When the holder is cut free, the commissure posts are released to expand and the holder may be removed using the handle. The inability to remove the elongate handle while maintaining commissure constriction is a detriment. The handle must be attached to the holder so that the commissure posts remain in a constricted position during attachment of the array of sutures to the sewing ring. This can be awkward for manipulation of the valve/valve holder combination during this time-constrained operation. Further, the relatively wide holder periphery may interfere with the attachment step.
What is needed then is an improved tissue-type prosthetic valve holder attachable to the inflow end of the valve that can constrict the commissure posts with or without a handle being attached, yet provides improved visibility and accessibility to the surgeon during the valve attachment steps.
The present invention provides a holder for a tissue-type prosthetic heart valve having an inflow end and an outflow end and a flow axis therebetween. The valve includes an annular suture ring at the inflow end attached to a stent having posts circumferentially-spaced about the flow axis that support occluding tissue surfaces of the valve. In this type of valve the posts are cantilevered generally in the outflow direction.
The holder includes a valve abutment portion sized and shaped to abut the suture ring at the inflow end of the valve. The holder further includes a commissure post constriction mechanism adapted to constrict the commissure posts radially inward from a relaxed position to a constricted position when actuated by a handle adapted to operatively connect to the commissure post constriction mechanism. A retaining mechanism is also provided that retains the commissure post constriction mechanism in the constricted position after the handle is removed.
In one embodiment the commissure post constriction mechanism comprises an adjusting portion and an adjusting member adapted to adjust the distance between the adjusting portion and the valve abutment portion and one or more filaments attached to the adjusting portion and sutured through the end of the commissure posts distal the adjusting portion. When the adjusting member is operated to separate the adjusting portion from the valve abutment portion the adjusting portion pulls the filaments, which in turn urge the end of the commissure posts distal the adjusting portion radially inwardly, to the constricted position.
The valve abutment portion may be of a planar shape, with the adjusting portion of a substantially complementary planar shape to the valve abutment portion. It is preferred that the planar shape of the valve abutment portion be comprised of a plurality of tangs radiating from a central body to each cover a portion of the suture ring. In this manner a sufficient amount of the suture ring is left exposed to allow for suturing the suture ring to the native annulus.
Adjustment of the distance between the valve abutment portion and the adjusting portion may be achieved by providing a central threaded aperture in the adjusting portion and an adjusting member that cooperates with this threaded aperture. In this construction the end of the adjusting member proximal the valve abutment portion abuts the valve abutment portion during operation. When the adjusting member is advanced through the central aperture of the adjusting portion it pushes the valve abutment portion and the two portions separate.
A handle may be operatively connected to the adjusting member to turn it by providing a handle that has an externally threaded end portion and an adjusting member having a central longitudinal threaded bore sized to receive the threaded end of the handle. When the handle is introduced into the bore it is rotated in a first direction and will seat in the threaded bore of the adjusting member. Further rotation of the adjusting member separates the adjusting portion from the valve abutment portion, as recited above, and causes the commissure posts to constrict inwardly.
In the prior art the handle would have to remain attached during suturing of the suture ring to the host tissue to keep the commissure posts in the constricted position. The holder with the handle connected were removed by severing the filament(s) and removing the holder, handle and filaments together.
In accordance with the present invention, the adjusting member itself may be adapted to be the retaining mechanism. Preferably, the adjusting member threads create a greater frictional resistance with the threaded aperture of the adjusting portion than that between the threaded end of the handle and the threaded bore of the adjusting member. This frictional resistance between the adjusting member and the central aperture allows the handle to be further rotated in a second, opposite direction, and the handle will detach or unscrew from the adjusting member without moving the adjusting member, leaving the commissure posts in the constricted position. The tug of the filaments themselves on the adjusting portion when the commissure posts will cause the adjusting member/central aperture thread interface to bind and so may be used to achieve the requisite additional frictional resistance required for allowing the handle to be unscrewed.
In alternative embodiments other mechanisms may be used in accordance with the invention to act as the retaining mechanism. For example, a ratchet assembly may be provided to lock the valve attachment and adjusting portions apart, allowing the handle to be removed while leaving the commissure posts in the constricted position. A ratchet assembly may be comprised of a one or more toothed members affixed to the valve abutment portion that each engage a complementary notch, opening or, for example, a pawl affixed to the adjusting portion. As the valve abutment portion and the adjusting portion are separated by the adjusting member the successive teeth of the toothed member engage the notch, opening or pawl affixed to the adjusting portion, locking the two portions apart.
The present invention further provides a method for retrofitting a holder for a tissue-type prosthetic mitral heart valve attachable to a surgical delivery handle. The heart valve is of the type having an inflow end and an outflow end and a flow axis therebetween, and includes an annular suture ring at the inflow end and radially flexible commissure posts circumferentially-spaced around the outflow end that support occluding tissue surfaces of the valve. The holder has a commissure post constriction mechanism releasably attached to the sewing ring at the inflow end of the valve, the mechanism adapted to constrict the valve commissure posts radially inward from a relaxed position to a constricted position when actuated by the delivery handle. The method includes providing a retaining mechanism that retains the commissure post constriction mechanism in the constricted position after the delivery handle is removed. The retaining mechanism may be provided during the holder assembly process so that the retaining mechanism is attached to and shipped as a unit with the prosthetic valve. Alternatively, the retaining mechanism may be provided separately from the holder and valve combination and the method includes coupling the retaining mechanism to the holder at the time of surgical implantation of the valve. The retaining mechanism and delivery handle may be packaged and sold as a unit. The retaining mechanism desirably comprises an adapter that is interposed between and threadingly engaged to the holder and the handle.
Further in accordance with the invention a method for replacing a heart valve is provided, comprising the steps of removing an existing heart valve to leave an annulus of that heart valve, attaching a holder of the invention to a prosthetic tissue-type heart valve and constricting the commissure posts of the prosthetic heart valve with a handle; inserting the valve through the annulus of the heart valve; removing the handle while leaving the commissure posts in the constricted position; suturing the tissue-type heart valve to the heart annulus, and detaching the holder from the prosthetic heart valve.
After suturing the heart valve to the annulus the surgeon severs the filament, causing the posts of the stent to open to the relaxed, operational position. The severing of the filament(s) also releases the holder from the prosthetic heart valve, allowing it to be removed.
A further understanding of the nature and advantages of the present invention are set forth in the following description and claims, particularly when considered in conjunction with the accompanying drawings in which like parts bear like reference numerals.

Method for retrofitting a heart valve holder


Generating and providing rich media presentations to a requesting device is described. Attributes of the requesting device are determined and used to create optimized code for the requesting device. The attributes may include information relating to the operating system of the requesting device; a media player; a bandwidth parameter; presence or absence of a firewall, permissions related to the requesting device, and the like. A virtual player is created that includes code to play media files. A presentation package is created that sets the presentation attributes for the multimedia experience. A media package is created that instructs the virtual player what multimedia content to play.

The Internet has seen expansive growth over the last several years. Not only are there more Web sites providing a wide range of information, service, and goods, there are more users on the Internet than ever before.
Today, users may experience multimedia clips, purchase goods, access the world's news as it happens, obtain reviews on various items or products in a variety of formats, or access a variety of resources all on the Internet. For example, a user may read product reviews, view pictures of a product, or in some instances, watch a video presentation related to the product.
In order to access the available resources, however, Internet users are exposed to a variety of different media types while visiting a Web site. Not only may users access textual information, they may also view graphical images, or watch multimedia presentations, including audio and video, that may be streamed or downloaded. The steps required to access this media, however, may be overwhelming to many of the users. Not only do certain sites require users to use particular products to access the media, many sites require the user to know the configuration of their system in order to play certain media files. For example, a user may have to download a particular media player, upgrade to a different version, or know the particular programs they are using on their system. With so many available options to access and play media files, users are constantly bombarded with different requirements.
Another requirement to view many multimedia sites is a high bandwidth connection to the Internet. Many sites rely on the user having a high bandwidth when streaming media to the user. While the majority of businesses today have access to broadband, the majority of home users connect to the Internet through a low speed dial-up modem resulting in a poor multimedia experience.

This patent is subject to a terminal disclaimer.

Generating and providing rich media presentations optimized for a device over a network

Dandia Audio KG Limited Liability Company