WO2006117184A2 - Composition veterinaire - Google Patents

Composition veterinaire Download PDF

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Publication number
WO2006117184A2
WO2006117184A2 PCT/EP2006/004083 EP2006004083W WO2006117184A2 WO 2006117184 A2 WO2006117184 A2 WO 2006117184A2 EP 2006004083 W EP2006004083 W EP 2006004083W WO 2006117184 A2 WO2006117184 A2 WO 2006117184A2
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WO
WIPO (PCT)
Prior art keywords
veterinary composition
treatment
osteoarthritis
composition
willow bark
Prior art date
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PCT/EP2006/004083
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English (en)
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WO2006117184A3 (fr
Inventor
Jennifer Ketzis
Wilfried Tiegs
Original Assignee
Novartis Ag
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Publication date
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Publication of WO2006117184A2 publication Critical patent/WO2006117184A2/fr
Publication of WO2006117184A3 publication Critical patent/WO2006117184A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/618—Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/76—Salicaceae (Willow family), e.g. poplar
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis

Definitions

  • This invention relates to methods and veterinary compositions for the prevention, metaphylaxis and treatment of osteoarthritis in a non-human animal. More particularly, the present invention relates to veterinary compositions and methods for reducing inflammation and pain associated with acute inflammation of body parts, particularly joints, due to injury or due to arthritic conditions or other disease conditions.
  • compositions which include analgesic and anti-inflammatory components, as well as components to protect against the abrasion of connective tissue and to support its production.
  • analgesic and anti-inflammatory components as well as components to protect against the abrasion of connective tissue and to support its production.
  • compositions Considering different side effects of current treatments, also a need for compositions remains to avoid side effects like dyspepsia, ulcer and gastrointestinal bleeding and designed for both, short-term and long-term treatment.
  • arthritis osteoarthritis and rheumatoid arthritis
  • navicular bone disease The most frequently occurring inflammatory diseases of the musculoskeletal system are: arthritis (osteoarthritis and rheumatoid arthritis) and navicular bone disease.
  • Arthritis is a disease that affects the joints. There are several forms, but the most common are osteoarthritis and rheumatoid arthritis. All forms of arthritis occur in humans and non- human animals. Moreover, there are many common minor pains, which are not arthritis but are due to injury, strain or inflammation of tendons and ligaments and are referred to as Soft Tissue Rheumatism.
  • Soft Tissue Rheumatism The name refers to aches or pains which arise from structures surrounding the joint such as tendons, muscles, bursae and ligaments. This disease complex may result from mechanical factors such as overuse or misuse of these structures or as a feature of an arthritis illness. Arthritis refers to inflammation within the joint which results in pain, swelling, and warmth around the joint and is often accompanied by difficulty in using the joint. Arthritis may lead to damage within the joint. This damage may be localized when pain is felt in one region or generalized when pain is felt either all over or in many parts of the body. Soft Tissue Rheumatism occurs not only in humans but is also a severe problem in the aging population of pets like cats but especially dogs. Diagnosing this disease in animals is more difficult than in humans where one can observe, for example the following common areas of localized Soft Tissue Rheumatism:
  • Trigger finger pain is felt along finger affected which sometimes has a feeling of snapping when extended - brought on by prolonged use of the hands.
  • Tennis elbow pain is felt along the outside of the elbow brought on by strenuous activities involving the outstretched arm.
  • Trochanteric Bursitis pain is felt on the outside of the hip joint and along the thigh due to inflammation of a bursa outside the hip.
  • Bursitis around the knee There are several bursae around the knee joint which can get inflamed due to pressure i.e. with prolonged kneeling or in association with Arthritis.
  • Heel pain can result from inflammation of the Achilles tendon or the tissue under the heel. Both result in pain and stiffness upon initiating walking and pain upon prolonged standing or climbing.
  • Bunions may give rise to pain on the sides of the forefoot.
  • Danger signs in soft tissue rheumatism are for example: The joint is red; hot, swollen, painful and difficult to move; muscles get smaller; bone appear crooked; rashes appear, lymph nodes enlarge; fever and chills develop, and there is loss of weight.
  • Osteoarthritis is a common disease that develops when linings of joints fail to maintain normal structure, leading to pain and decreased mobility. It is associated with aging and injury (it used to be called “wear-and-tear” arthritis), and can occur secondary to many other conditions. However, in most cases its true cause remains unknown. It is a degenerative disease that most often affects the fingers, neck, lower back, hips, knees, and other joints. It is more common with age and in cases of injury to the joint, overuse of joints and with excess weight. For example, in USA over 20 million individuals have osteoarthritis. Over 50% of people develop this condition by the age of 65. Osteoarthritis is a common disease not only in men but also well known in dogs.
  • Rheumatoid arthritis affects over 2 million people, more than 60% of them are women.
  • the disease usually begins in the young to middle adult years.
  • the characteristic symptoms of inflammatory arthritis are swelling and pain of one and more joints. The affected joints are often warmer than the other joints of the body. Stiffness of the joints when getting up in the morning, or after resting for a time, is very common and is sometimes the first symptom.
  • Rheumatoid arthritis occurs not only in humans but also frequently in pets. This condition can be seen of cats and dogs of any age. Symptoms to look for: reluctance to walk, reduced motion, limping or favoring one side of the body, lethargic, fever, loss of appetite, obvious pain and discomfort.
  • Navicular Bone Disease is a complicated disease that is a common cause of lameness in horses. The disease results in degenerative changes to the navicular bone, the cartilage and the deep digital flexor tendon. Often the disease is primarily associated with the cartilage and the tendons rather than the bone. NBD has to be treated by elaborate methods but nevertheless almost always results in the loss of the affected, but otherwise healthy, horse. NBD strikes all horse breeds and usually occurs in 6-12-year-old horses. NBD starts insidiously but can be detected without exception already at a stage in which the horse does not show any symptoms yet.
  • NBD usually occurs only in the horse's front feet, is most common in middle to heavyweight hunter types, particularly those that are kept as hacks rather than racehorses or show- jumpers and is extremely rare in ponies.
  • Factors that could be influential here are the weight of the horse in proportion to the size of his hoof and also protection against navicular may be gained from the long, slow fitness work that competition animals undergo and grazing ponies do naturally.
  • the inflammation of the affected bone is also treated with steroidal and nonsteroidal anti-inflammatory drugs.
  • these methods are only partly successful, their efficiency is difficult to assess, they are elaborate and, in particular, they do not achieve a permanent cure of the disease. Accordingly, there is still an urgent need to solve the problem.
  • the present invention is based on the discovery that the combination of the natural products Willow Bark and Mussel extract, eventually further combined with Boswellic Acid, results in a beneficial effect in the prophylaxis and therapy of a broad range of inflammatory diseases. Said three natural components are characterized below. It has now surprisingly been found that the administration of the veterinary compositions, as defined in the claims, to a non- human animal suffering from one or more of the above-referenced diseases results in a significant and sustained improvement of the quality of life and a significant reduction of pain caused by the disease.
  • inventive compositions do not only show a beneficial effect on the symptoms but actually act as a disease modifier, i.e. exhibit a real curative effect.
  • beneficial effect of the inventive composition on NBD in horses is their relatively long duration of efficacy and ability to use long-term without adverse effects.
  • chondroprotective combinations e.g., glucosamine, chondroitin
  • this combination does not require 4-6 weeks to have an impact on pain relief; instead, relief is achieved in 2-3 weeks.
  • compositions according to this invention have a very positive influence on the formation of bones and cartilage. Unexpectedly, these compositions do not show any undesired side effects even if they are highly overdosed.
  • non-human animals can be the target for this kind of treatment.
  • the expression non-human animals includes farm animals, such as cows, pigs, sheep and goats, poultry, such as hens, turkeys and geese, animals bred for their fur, such as mink, foxes, chinchillas, rabbits and the like, as well as domestic animals and pets, such as cats and dogs.
  • Preferred target animals are farm animals and especially pets suffering from one or more diseases described herein before.
  • One important target animals the population of aging pets, especially cats and dogs.
  • Another preferred target group consists of hoofed animals, especially horse, and meat producing animals used for breeding, especially pigs.
  • Other non-human animals are of course not excluded.
  • the active ingredients used in this treatment are substances that are commercially available as standardized products. They are natural extracts and show the following characteristics: Willow Bark or Salicis cortex consists of the bark of the young, 2-3-year-old branches harvested during early spring of Salix alba L, S. purp ⁇ res L, S. fragilis L. and other comparable Salix species (Salicaceae), as well as their preparations in effective dosage. The bark contains at least 2 percent total salicin derivates, calculated as salicin and related to dried herb. Antipyretic, analgesic and antiphlogistic effects are described for the willow bark. Administration of Willow Bark leads to positive effects in non-human animals suffering from arthritis. Positive effects are recognized in the symptoms that accompany this disease, i.e. fever, rheumatic ailments and headaches. For Willow Bark the same is true as for the other substances characterized herein, namely that much better results are obtained after the administration of a combination of products rather than by applying only one component.
  • the recommended daily dosage for Willow Bark extract is a therapeutically effective amount that is for most non-human animals generally from about 5 to about 1 ,000 mg/kg/day, preferably from about 10 to about 500 mg/kg/day, more preferably from about 15 to about 150 mg/kg/day.
  • Mussel extract In context with the present invention the extract of the New-Zealand green- lipped mussel (Perna canaliculus) [GLME] is most preferred and contains substances having a beneficial anti-inflammatory effect.
  • the preparation of the Mussel extract is described in the New Zealand patent application No. 328489, which relates to an anti-inflammatory composition including a freeze-dried substance containing proteins.
  • the product containing the substance extracted from green-lipped mussel possesses chondroprotective, gastro protective and anti-inflammatory activity and is beneficial to sufferers of many of the arthritic disorders. It has now been found that the beneficial effect of the Mussel extract can be significantly increased through combination with one or more substances described herein.
  • GB2347349 describes a synergistic pharmaceutical composition for treating inflammation in non-human animals, comprising proteins extracted from the New Zealand green-lipped mussel and one or more glycosaminoglycans, such as glucosamine or glucosamine sulphate.
  • This reference further describes the anti-inflammatory properties of said pharmaceutical composition.
  • This composition may be used in the treatment of arthritis conditions, such as osteoarthritis or rheumatoid arthritis.
  • EP0982034 is a further reference that describes a composition containing an extract of the New-Zealand green-lipped mussel and glucosamine for the treatment of osteoarthritis in humans and non-human animals.
  • This reference further describes a method for preparing green-lipped mussel extract containing by weight 0.65-3.21 % of moisture, 0.67-10.54 % of lipids, 52.13-55.6 % of carbohydrates and 11.7-14.9 % of ash. This is a very suitable extract for the present invention.
  • WO0101976 describes use of methylsulfonylmethane and glucosamine, or salts thereof, in combination with at least one component derived from Perna canaliculus for the support, regeneration, and repair of connective tissues, in both animals and humans. Specifically mentioned is osteoarthritis and rheumatoid arthritis.
  • the Perna canaliculus component is for example freeze-dried ground whole mussel.
  • the recommended daily dosage for Mussel extract is a therapeutically effective amount that is for most non-human animals generally from about 5 to about 1 ,000 mg/kg/day, preferably from about 10 to about 500 mg/kg/day, more preferably from about 20 to about 250 mg/kg/day.
  • Boswellic Acid from Boswellia serrata a large, branching deciduous tree, which grows in India.
  • the gum resin that exudates from the tree has been used in the Ayurverdic system of medicine for the management of arthritis, respiratory disease, and liver disorders. These active principles are found in the gum resin.
  • the major use of Boswellia serrata in contemporary medicine is an anti-arthritic and anti-inflammatory pharmacologic agent. It has been observed that combination of Boswellic acids represent effective non-steroidal antiinflammatory compounds (NSAID ' s) with broad biological activities yet without NSAID ' s characteristic gastrointestinal side effects. Boswellic acids were found to inhibit two antiinflammatory enzymes, 5-lipooxygenase and Human Leukocyte Elastase (HLE).
  • Boswellic acids have been found effective in alleviation of rheumatoid arthritis and osteoarthritis. The administration of Boswellic acids reduces significantly the mean arthritis score (sum of symptoms and the biochemical index of inflammations). It has now been recognized that significantly better results are obtained if Boswellic acids are not administered alone but in combination with one or more of the substances described herein. In combination with one or more of the other active ingredients Boswellic acids exhibit a significant gastro-protective effect.
  • the recommended daily dosage for Boswellic acids is a therapeutically effective amount that is for most non-human animals generally from about 1 to about 500 mg/kg/day, preferably from about 2 to about 100 mg/kg/day, more preferably from about 2 to about 25 mg/kg/day.
  • glucosamine glucosamine
  • chondroitin sulfate a biologically effective amount of additional natural products such as glucosamine, and chondroitin sulfate.
  • the recommended daily dosage for glucosamine is generally about 1 to about 400 mg/kg/day, preferably about 10 to about 90 mg/kg/day, more preferably about 20 to about 40 mg/kg/day; for chondroitin sulfate it is generally about 1 to about 500 mg/kg/day, preferably about 20 to about 150 mg/kg/day, more preferably about 30 to about 90 mg/kg/day.
  • It is a primary objective of the present invention to provide a veterinary composition comprising a mixture of Willow Bark and at least one further active ingredient selected from the group consisting of Mussel Extract and Boswellic acid, together with a physiologically acceptable carrier.
  • This pharmaceutical composition is very suitable for treating acute and chronic inflammation in non-human animals and shows a very positive curing effect with regard to the bone-related diseases discussed above.
  • said veterinary composition is administered orally to a non- human animal either as a prophylactic or curative treatment.
  • Part of the present invention is a veterinary composition for oral administration which, when ingested, is effective in treating pain and discomfort of inflammatory ailments such as, but not limited to, rheumatoid arthritis, osteoarthritis, hip dysplasia, juvenile rheumatoid arthritis, soft tissue rheumatism, gout, low back pain, afflictions, sprains, headache, backache, and general muscle soreness after exercise and exertion. It is still another object of the present invention to provide a composition to be administered orally which improves the general health, quality of life, and well being of those non-human animals suffering from chronic inflammatory diseases, including rheumatism and arthritis.
  • inflammatory ailments such as, but not limited to, rheumatoid arthritis, osteoarthritis, hip dysplasia, juvenile rheumatoid arthritis, soft tissue rheumatism, gout, low back pain, afflictions, sprains, headache, backache, and general muscle so
  • NSAIDs Non-Steroidal Anti- Inflammatory Drugs
  • a veterinary composition comprising a mixture of an effective amount of Willow Bark and Mussel Extract together with a physiologically acceptable carrier.
  • a veterinary composition comprising in addition to an effective amount of Willow Bark and Mussel Extract and also an effective amount of Boswellic acid.
  • a veterinary composition comprising a daily dosage from about 5 to about 1 ,000 mg/kg/day of Willow Bark and from about 5 to about 1,000 mg/kg of Mussel extract, preferably together with a daily dosage from about 1 to about 500 mg/kg/day of Boswellic acid.
  • composition containing in addition an effective amount of glucosamine and/or chondroitin sulfate.
  • a preferred embodiment of this invention consists in a veterinary composition comprising a daily dosage of about 10 to about 500 mg/kg Willow Bark, of about 10 to about 500 mg/kg Mussel Extract and of about 2 to about 100 mg/kg Boswellic acids. • Even more preferred is such a veterinary composition if it comprises in addition a daily dosage of 1 to 400 mg/kg glucosamine and/or 1 to 500 mg/kg chondroitin sulfate.
  • a preferred embodiment consists of a method for the prevention, metaphylaxis or treatment of osteoarthritis in a non-human animal and/or for reducing inflammation and pain associated with acute inflammation of body parts. This method comprises the administration of a composition as set out before.
  • Another preferred embodiment consists of the use of one of said veterinary compositions in a method for the prevention, metaphylaxis or treatment of osteoarthritis in a non-human animal.
  • Preferred is also the use of a combination of Willow Bark and Mussel Extract and optionally Boswellic acid in the manufacture of a veterinary composition for the prevention, metaphylaxis or treatment of osteoarthritis in a non-human animal, especially for reducing inflammation and pain associated with acute inflammation of body parts and/or for reducing inflammation and pain associated with acute inflammation of body parts, particularly joints, due to injury or due to arthritic conditions or other disease conditions.
  • a further preferred embodiment is a such a veterinary composition for the prevention, metaphylaxis or treatment of osteoarthritis in a non-human animal.
  • the preferred treatment is the oral administration of one of the described veterinary compositions.
  • the active ingredients of the present invention can be combined with further beneficial substances, such as vitamins, e.g. from the B series or manganese salts.
  • a dosage for the composition for oral treatment of the present invention may consist of one or more capsules or tablets for non-human animal oral consumption.
  • the dosage ranges defined herein before are meant per 1 Kg bodyweight per day.
  • This dosage may be administered in a single daily dosage form in which all components are present.
  • the nutritional supplement compositions for the present invention may be administered more than once, preferably twice, per day.
  • the number of daily administrations will depend upon the needs of the non-human animal recipient. Different connective tissue disorders and injuries may require different amounts of the compositions of the present invention. In those regards, several dosages may be administered depending on the particular needs of the non-human animal.
  • compositions for the present invention may for example be administered in scoops.
  • compositions of the invention may be made by conventional methods.
  • the above-described ingredients are combined as the active ingredient in intimate admixture with a suitable carrier according to conventional compounding techniques.
  • the carrier must be a physiologically acceptable carrier and may take a wide variety of forms depending upon the form of preparation desired for administration.
  • any usual veterinary medium may be employed.
  • oral liquid preparations e.g., suspensions, elixirs, feed additive, and solutions
  • media containing for example, water, oils, alcohols, flavoring agents, preservatives, coloring agents and the like may be used.
  • Physiologically acceptable carriers such as starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like may be used to prepare solid oils (e.g., powders, capsules, pills, caplets, tablets, microencapsulated granules, micro-tablets, coated granules and lozenges).
  • Capsules or tablets are the preferred oral dosage form.
  • Controlled release forms may also be used. Because of their ease in administration, lozenges, tablets, pills, caplets, and capsules represent the most advantageous oral dosage unit form, in which case solid veterinary carriers are obviously employed. If desired, tablets may be sugar coated or enteric coated by standard techniques.
  • the compositions of the present invention may be in form of one or more of these oral dosage forms, i.e. a single dosage may be in multiple forms.
  • the adjuvants known from the medical and veterinary practice for oral galenic forms can be used.
  • Suitable physiologically acceptable carriers are in particular fillers, such as sugars, e.g. lactose, saccharose, mannitol or sorbitol, cellulose preparations and/or calcium phosphates, e.g. tricalcium phosphate or calcium hydrogen phosphate, in a broader sense also binders, such as starch pastes using e.g. corn, wheat, rice or potato starch, gelatin, tragacanth, methyl cellulose and/or, if desired, disintegrants, such as the above-mentioned starches, in a broader sense also carboxymethyl starch, cross-linked polyvinylpyrrolidone, agar, alginic acid or a salt thereof, such as sodium alginate.
  • fillers such as sugars, e.g. lactose, saccharose, mannitol or sorbitol, cellulose preparations and/or calcium phosphates, e.g. tricalcium phosphate or calcium hydrogen
  • Excipients are especially flow conditioners and lubricants, for example silicic acid, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and/or polyethylene glycol.
  • Tablet cores may be provided with suitable, where appropriate enteric, coatings, using inter alia concentrated sugar solutions which may comprise gum arabic, talc, polyvinylpyrrolidone, polyethylene glycol and/or titanium dioxide, or coating solutions in suitable organic solvents or solvent mixtures, or, for the preparation of enteric coatings, solutions of suitable cellulose preparations, such as acetylcellulose phthalate or hydroxypropylmethylcellulose phthalate.
  • Dyes, flavours or pigments may be added to the tablets or tablet coatings, for example for identification purposes or to indicate different doses of active ingredient.
  • compositions include hard capsules consisting of gelatine, and also soft, sealed capsules consisting of gelatine and a plasticizer, such as glycerol or sorbitol.
  • the hard capsules may contain the active ingredient in the form of granules, for example in admixture with fillers, such as lactose, binders, such as starches, and/or glidants, such as talc or magnesium stearate, and where appropriate stabilizers.
  • the active ingredients are preferably dissolved or suspended in suitable liquids, such as fatty oils, paraffin oil, or liquid polyethylene glycols, and stabilizers may likewise be added.
  • suitable liquids such as fatty oils, paraffin oil, or liquid polyethylene glycols, and stabilizers may likewise be added.
  • capsules which can be both easily, chewed and also swallowed whole, are preferred.
  • compositions of the invention can be prepared in a known manner, e.g. for example by means of conventional mixing, granulating, coating, dissolving or lyophilizing methods.
  • Veterinary compositions for oral administration can be obtained, for example, by combining the active ingredients with solid carriers, granulating a resulting mixture where appropriate, and processing the mixture or granules, if desired or necessary, to form tablets or tablet cores following the addition of suitable excipients.
  • the active ingredients Willow Bark, Mussel Extract and Boswellic acid are used in these compositions in standardized solid form and preferably together with - at least - one of the adjuvants conventionally employed in the art of formulation, such as extenders, e.g. solvents or solid carriers, or surface-active compounds (surfactants).
  • adjuvants conventionally employed in the art of formulation, such as extenders, e.g. solvents or solid carriers, or surface-active compounds (surfactants).
  • extenders e.g. solvents or solid carriers
  • surfactants surface-active compounds
  • compositions (drugs) for non-human animals form the most important aspect of the invention.
  • active ingredient is understood to mean the sum of one or more of the natural products named in claim 1.
  • EXAMPLE 1 Tablets containing a mixture of at least two active ingredients selected from the group consisting of Mussel extract, Boswellic acid, Willow Bark, glucosamine, and chondroitin sulfate can be prepared as follows:
  • composition for 1000 tablets
  • Tablets (each containing a total of 0.0183 g active ingredient) are prepared as follows: Composition (for 10,000 tablets)
  • Ethanol q.s. A mixture of the active ingredient, the lactose and 274.70 g potato starch is wetted with an ethanolic solution of stearic acid and granulated through a sieve. After drying, the remaining potato starch, the talc, the magnesium stearate, and the colloidal silica are added and the mixture compressed to form tablets of 0.1 g each in weight, which - if so desired - can be scored to allow for a finer adjustment of the dose.
  • EXAMPLE 2 Capsules: each containing a total of 0.022 g active ingredient can be prepared as follows:
  • Composition for 1000 capsules
  • the active ingredient is mixed with the lactose, the mixture wetted evenly with an aqueous solution of the gelatine and granulated through a sieve with a mesh size of 1.2-1.5 mm.
  • the granulate is mixed with the dried corn starch and the talc, and portions of 300 mg are filled into hard gelatine capsules.
  • the methylcellulose is first stirred into water. After the material has swollen, the silicic acid is stirred in and the mixture homogeneously suspended. The active ingredient and the corn starch are mixed. The aqueous suspension is worked into this mixture and kneaded to dough. The resulting mass is granulated through a 12 M sieve and dried. In a further step, all components are thoroughly mixed. Finally, the pre-mixtures resulting from the first two partial steps are mixed and compressed to form boli.
  • EXAMPLE 7 The composition of the present invention is made in one or more tablets or capsules for oral administration in small animals.
  • each daily dosage contains per kg bodyweight:
  • EXAMPLE 8 For those situations in which glucosamine supplementation is desired, glucosamine will be added to the composition of Example 1 , so that in another preferred embodiment each daily dosage contains per kg bodyweight:
  • EXAMPLE 10 For those situations in which glucosamine and chondroitin sulfate supplementation is desired, but not Boswellic acid, Mussel extract will be excluded to the composition of Example 3, so that in another preferred embodiment each daily dosage contains per kg bodyweight:
  • EXAMPLE 11 For those situations in which glucosamine is desired, but not Boswellic acid, Mussel extract will be excluded to the composition of Example 2, so that in another preferred embodiment each daily dosage contains per kg bodyweight:
  • EXAMPLE 13 For those situations in which glucosamine Mussel extract and Willow bark supplementation is desired, but not chondroitin sulfate, chondroitin sulfate will be excluded to the composition of Example 6, so that in another preferred embodiment each daily dosage contains per kg bodyweight:
  • a very favorable veterinary composition contains as a daily dosage per kg bodyweight:
  • EXAMPLE 16 For larger animals, such as horses, the composition of Example 3 is administered as filled scoops.
  • Example A Osteoarthritis in dogs.
  • Group 2 receiving the test product that contains per tablet 250 mg Green-lipped Mussel extract, 25 mg Boswellin Forte® (highly purified extract), 200 mg White Willow Bark.
  • Group 3 receiving as reference product no. 1 Cosequin DS Chewable Tablets (commercial product) consisting of containing as active ingredient a mixture of Glucosamine HCL and Chondroitin sulphate.
  • Group 4 receiving as reference product no. 2 Connectin Tablets (commercial product) consisting of containing as active ingredient a mixture of Glucosamine HCL, Chondroitin sulfate, Yucca Root, Alfalfa, Devil ' s Claw, Nettle Leaf, Tumeric, Ginger Root, Black Cohosh, Celery Seed, Cayenne Pepper. Trial length: 56 days.
  • Test product and placebo is one tablet per 10 Kg bodyweight per day. Cosequin and Connectin are used according to package labels.
  • Radiographs to select dogs for the trial are taken to ensure that the dog has osteoarthritis.
  • Detailed veterinary examinations including physical examination and blood samples for hematology and plasma biochemistry are performed between days -7 and -1 (pretreatment) and at 28 and 56 days after initiation of treatment to determine tolerability of the test product.
  • the physical examinations include an assessment of attitude, body condition, hydration status, heart rate, rectal temperature, mucous membrane color and capillary refill time, thoracic auscultation, and abdominal palpation.
  • the blood samples are analyzed for chemistry parameters, including protein, urea, creatinine, alkaline phosphatase (ALP), and alanine amino transferase (ALT) and for hematology parameters, including RBC count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) 1 mean corpuscular hemoglobin concentration (MCHC), and red blood cell count (RBC).
  • chemistry parameters including protein, urea, creatinine, alkaline phosphatase (ALP), and alanine amino transferase (ALT)
  • hematology parameters including RBC count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) 1 mean corpuscular hemoglobin concentration (MCHC), and red blood cell count (RBC).
  • an orthopaedic examination weight baring, willingness to hold contralateral limb, mobility of the effected joint on manipulation, pain on palpation, swelling, and lameness
  • pressure plate analysis to measure the dogs' gaits
  • the outcome of the comparative test shows a clear advantage of the test product over the placebo and demonstrates equivalency or advantage over the two reference products in many of the categories measured to determine efficacy.
  • the test product is statistically better than the placebo and the reference products in improving the range of motion of the joint, better than one reference product in decreasing the level of pain, shows an overall better cumulative orthopaedic score compared to the placebo and one reference product, and has a better overall improved score compared to placebo.
  • Neither of the reference products has statistically significant (p ⁇ 0.1) changes compared to placebo for any of the categories measured in the orthopaedic examination. These changes are based on the average of the scores on Days 28 and 56 compared to baseline data.
  • test product is well tolerated.
  • the change from baseline of the mean corpuscular volume (hematology) and the total protein (blood chemistry) is higher in the test group compared to placebo and the mean corpuscular hemoglobin concentration is lower compared to placebo (p ⁇ 0.05), but were within normal ranges and were not considered clinically significant.
  • the skin and coat assessment of the test group shows improved skin and coat condition over the placebo and one reference product (p ⁇ 0.05).

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Abstract

L'invention concerne une composition vétérinaire comprenant un mélange d'extrait d'écorce de saule et de moules, éventuellement combiné à de l'acide boswellique, associé à un support physiologiquement acceptable. Ladite composition peut être utilisée pour la prévention, la métaphylaxie et le traitement de l'ostéoarthrite chez un animal non humain et plus particulièrement, pour réduire l'inflammation et la douleur associée à une inflammation aiguë de parties corporelles d'un animal non humain, notamment les articulations, due à une lésion ou due à des affections arthritiques ou à d'autres affections pathologiques.
PCT/EP2006/004083 2005-05-03 2006-05-02 Composition veterinaire WO2006117184A2 (fr)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITVR20080127A1 (it) * 2008-11-18 2010-05-19 Phytonature Sas Nuova associazione di estratti naturali per il controllo dei mediatori chimici dell'infiammazione e la conseguente riduzione della risposta infiammatoria.
WO2010085158A1 (fr) * 2009-01-20 2010-07-29 Bomac Research Limited Traitement des animaux amélioré
WO2010114396A1 (fr) * 2009-03-31 2010-10-07 Bomac Research Limited Administration de médicament
CN102391499A (zh) * 2011-09-20 2012-03-28 同济大学 一种还原刺激下快速释放乳香酸活性成分的聚合物的制备方法
JP2015067563A (ja) * 2013-09-27 2015-04-13 小林製薬株式会社 経口組成物
CN107519362A (zh) * 2017-10-16 2017-12-29 耿峰 一种中药贴膏及其制备方法和用途

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998052583A1 (fr) * 1997-05-23 1998-11-26 Bernard Weisman Composition naturelle destinee a traiter les inflammations articulaires
GB2347349A (en) * 1997-05-21 2000-09-06 Macfarlane Lab New Zealand Lim A synergistic composition comprising mussel protein extract and glycosaminoglycan suitable for treatment of arthritis
KR20030005116A (ko) * 2002-12-02 2003-01-15 주식회사 아미노젠 천연 약재 추출물을 함유하는 항염증제 조성물 및 이를유효성분으로 하는 기능성식품

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2347349A (en) * 1997-05-21 2000-09-06 Macfarlane Lab New Zealand Lim A synergistic composition comprising mussel protein extract and glycosaminoglycan suitable for treatment of arthritis
WO1998052583A1 (fr) * 1997-05-23 1998-11-26 Bernard Weisman Composition naturelle destinee a traiter les inflammations articulaires
KR20030005116A (ko) * 2002-12-02 2003-01-15 주식회사 아미노젠 천연 약재 추출물을 함유하는 항염증제 조성물 및 이를유효성분으로 하는 기능성식품

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BUDSBERG S C ET AL: "Nutrition and Osteoarthritis in Dogs: Does It Help?" VETERINARY CLINICS OF NORTH AMERICA - SMALL ANIMAL PRACTICE 2006 UNITED STATES, vol. 36, no. 6, 3 November 2006 (2006-11-03), pages 1307-1323, XP009078754 ISSN: 0195-5616 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITVR20080127A1 (it) * 2008-11-18 2010-05-19 Phytonature Sas Nuova associazione di estratti naturali per il controllo dei mediatori chimici dell'infiammazione e la conseguente riduzione della risposta infiammatoria.
WO2010085158A1 (fr) * 2009-01-20 2010-07-29 Bomac Research Limited Traitement des animaux amélioré
WO2010114396A1 (fr) * 2009-03-31 2010-10-07 Bomac Research Limited Administration de médicament
CN102391499A (zh) * 2011-09-20 2012-03-28 同济大学 一种还原刺激下快速释放乳香酸活性成分的聚合物的制备方法
JP2015067563A (ja) * 2013-09-27 2015-04-13 小林製薬株式会社 経口組成物
CN107519362A (zh) * 2017-10-16 2017-12-29 耿峰 一种中药贴膏及其制备方法和用途

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GB0508991D0 (en) 2005-06-08

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