• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Use of paracetamol and ibuprofen in the manufacture of a medicament for the treatment of osteoarthritis or rheumatoid arthritis, which medicament comprises a combination composition comprising about 125 mg to about 150 mg ibuprofen and about 475 mg to about 500 mg paracetamol.
    公开号:CH702339B1
    申请号:CH00658/11
    申请日:2009-10-12
    公开日:2016-06-15
    发明作者:Campbell Atkinson Hartley
    申请人:Aft Pharmaceuticals Ltd；
    IPC主号:
    专利说明:

    Technical area
    The invention relates to the use of paracetamol and ibuprofen for the manufacture of a medicament for the treatment of osteoarthritis or rheumatoid arthritis.
    background
    Tablets with a combination of paracetamol (about 475 mg to about 500 mg) and ibuprofen (about 125 mg to about 150 mg) are known from the published patent application WO 2006/004 449 by AFT Pharmaceuticals. This WO application discloses the use of such a combination for reducing pain after dental surgery. It has now been found that combinations of paracetamol and ibuprofen are sufficient to produce surprising synergistic results when used to reduce symptoms associated with osteoarthritis and rheumatoid arthritis.
    Osteoarthritis can include inflammation of the joints resulting from abnormal wear and tear on the cartilage used to cushion the joint and a concomitant reduction in the synovial fluid that lubricates the joint. Since the bone surfaces in the joint are less and less protected, the patient suffers pain when the affected joints have to bear the normal body weight, for example when standing or walking. This can develop to the point where muscles atrophy and adhesive tapes loosen. Rheumatoid arthritis is an autoimmune disease that can include attacks by the immune system on the joints, which also causes inflammation. This can be a severely debilitating and painful condition that leads to loss of mobility through pain.
    Paracetamol in a dosage of 4,000 mg / day, taken in four doses of 1,000 mg each, is considered sufficient to relieve pain of low intensity or for an analgesic effect, but is not sufficiently effective for many patients to achieve relief which is required for moderate to severe osteoarthritis or moderate to severe rheumatoid arthritis. It is known to treat moderate to severe osteoarthritis with ibuprofen in doses of up to 2,400 mg per day (i.e., in three doses of 800 mg each). Ingesting ibuprofen in this amount is viewed as an anti-inflammatory treatment rather than purely analgesic treatment (for analgesic treatment with ibuprofen, a patient would normally only take up to 1,200 mg / day in three doses of 400 mg each). Anti-inflammatory treatment with ibuprofen at 2,400 mg / day from three doses, however, can lead to undesirable side effects, for example negative cardiorenal conditions, risk of thrombosis and gastrointestinal bleeding. Reducing the daily dose of ibuprofen reduces the risk of such side effects, but at the same time leads to significantly less pain and / or inflammation relief.
    For many patients suffering from osteoarthritis or rheumatoid arthritis, combined ibuprofen / paracetamol treatment significantly reduces the daily dose of ibuprofen that would otherwise be required to provide adequate pain relief. Thus, for some patients, the risk of side effects normally attributable to high doses of ibuprofen can be substantially reduced without compromising the patient's condition, or at least not to a significant extent.
    Summary of the invention
    According to the invention, a use of paracetamol and ibuprofen in the manufacture of a medicament for the treatment of osteoarthritis or rheumatoid arthritis is provided, the medicament comprising a combination composition comprising ibuprofen and paracetamol, for administration in doses which are suitable, 250 mg to 300 mg Deliver ibuprofen and 950 mg to 1,000 mg paracetamol per dose.
    Preferably, a use of paracetamol and ibuprofen in the manufacture of a medicament for the treatment of osteoarthritis or rheumatoid arthritis is provided, the medicament being a combination composition with dosage units of 125 mg to 150 mg of ibuprofen and 475 mg to 500 mg of paracetamol for the administration of two Includes dosage units per dosage.
    The medicament is preferably used to treat osteoarthritis.
    Preferably the composition comprises about 150 mg ibuprofen and about 500 mg paracetamol.
    Preferably the composition comprises 150 mg ibuprofen and 500 mg paracetamol.
    Preferably, the medicament is to be taken in two dosage units up to four times a day.
    The medicament is preferably to be taken in two dosage units four times a day.
    [0013] The dosage units are preferably tablets or capsules.
    Preferably, the medicament is presented as pharmaceutical packaging with tablets or capsules, the packaging including instructions for the user not to take two tablets or capsules each time more than 4 times within 24 hours or at intervals of not more than 6 hours.
    The composition is preferably used to deliver approximately 300 mg ibuprofen and approximately 1,000 mg paracetamol per dose.
    The composition is preferably used to deliver 300 mg ibuprofen and 1,000 mg paracetamol per dose.
    Preferably, the composition is provided with instructions that 300 mg ibuprofen and 1,000 mg paracetamol should be taken with each dose administration four times a day.
    [0018] The composition is optionally in the form of one or more solid dosage units.
    [0019] Optionally, the composition is in liquid form.
    Preferably the amount of ibuprofen is approximately 300 mg and the amount of paracetamol is approximately 1,000 mg per administration.
    The amount of ibuprofen is preferably 300 mg and the amount of paracetamol is 1,000 mg per administration.
    Ibuprofen and paracetamol are preferably in the form of one or more combination tablets or capsules.
    Preferably, ibuprofen and paracetamol are administered or taken in the same manner at approximately 6 hour intervals.
    Brief description of the drawings
    In the following, some preferred embodiments of the invention are described purely by way of example and with reference to the accompanying drawings. 1 shows the effectiveness of a preferred form of the present invention in connection with WOMAC pain scores; and FIG. 2 further shows the effectiveness of a preferred form of the invention in connection with global pain classification scores.
    Detailed description
    A preferred embodiment of the invention provides a tablet which contains about 125 mg to about 150 mg ibuprofen and about 475 mg to about 500 mg paracetamol in combination. Most preferably the ibuprofen or paracetamol content of the tablet is approximately 150 mg and approximately 500 mg, respectively. By taking two tablets every 6 hours, a patient can receive a total of 1,200 mg ibuprofen and 4,000 mg paracetamol over a 24 hour period. Alternatively, the tablet can be dosed twice so that only one tablet is required to deliver 250 mg to about 300 mg ibuprofen and about 950 mg to about 1,000 mg paracetamol in combination.
    The relief achievable by taking two tablets up to four times a day is sufficient at least for some patients suffering from osteoarthritis or rheumatoid arthritis, especially the moderate to severe forms of these conditions. This is surprising since moderate to severe osteoarthritis and rheumatoid arthritis are inflammatory conditions and the amounts of ibuprofen and paracetamol delivered by two tablets at each dose would not be expected to significantly alleviate the symptoms caused by such inflammation. However, when ibuprofen and paracetamol are combined in amounts of about 250 to 300 mg and 1,000 mg, respectively (in one or two tablets, for example), considerable benefit is obtained, especially when such treatment is repeated at 6 hour intervals. For osteoarthritis at least, one would find much larger amounts of ibuprofen to be required, for example taking 800 mg three times over a 24 hour period (i.e., 2,400 mg / day) for the treatment of at least moderate to severe cases. The combination therapy described herein is sufficient to provide relief to at least some patients suffering from mild, moderate, or severe osteoarthritis, and is particularly helpful for some patients in cases of moderate to severe osteoarthritis.
    Clinical study
    To exemplify the effectiveness of a preferred embodiment of the invention, a prospective, randomized, double-blind study was carried out to measure the effect on patients suffering from osteoarthritis. Four patient groups were selected and each group was given one of the following medications over a period of four weeks:
    All patients were between the ages of 45 and 80 years and had been suffering from chronic knee pain due to osteoarthritis for at least 6 months. Patients went through a washout period to eliminate their existing osteoarthritis treatments. The first three groups had 8 patients each, the fourth group started with 9 patients. One of the patients in the fourth group did not complete the study. At the start of the study and also at the end of each subsequent week, patients had to see a doctor and fill out a WOMAC questionnaire and a global pain rating.
    The WOMAC questionnaire included a series of questions related to the pain intensity felt by the patient. Patients were asked to quantitatively mark their answers to each question separately using an analog scale 100 mm long. The differences in the scores at the beginning and at the end of the study were compared. The mean decrease in the WOMAC pain scores is shown graphically in FIG. It can be seen that the patients in the “Combination” group achieved significantly better pain relief than those in the “Paracetamol” and “Ibuprofen low dose” groups. In fact, patients in the “Combination” group experienced practically equivalent relief to those in the “Ibuprofen High Dose” group, but without the same risk of undesirable side effects.
    The global pain rating assessment comprised four categories. These were: • None (no pain); • Mild (perceived pain but not disrupting daily routine actions); • Moderate (perceived pain sufficient to limit or decrease daily routine actions); • Difficult (unable to work or perform daily routine).
    At the beginning of the study and at the end of each subsequent week, patients rated their pain intensity according to one of these categories. The improvement in the patient scores was evaluated. For example, patients who started with the pain rating of “moderate” and then had the pain rating of “slight” at the end of the study improved by 1 rating group. As a further example, patients who had started with the pain rating of "severe" and then ended the study with the pain rating of "slight" improved by 2 assessment groups. The mean improvement in the patients in each group, as measured by the number of grading groups, was scored and graphed as shown in FIG. The graph shows that the patients in the “Combination” group achieved significantly better pain relief than those in the “Paracetamol” and “Ibuprofen low dose” groups. It also shows that the patients in the “Combination” group achieved better pain relief than those in the “Ibuprofen High Dose” group, but again without the same risk of negative side effects.
    Patients were also asked to keep records of negative side effects, if any. No confirmed or probable negative side effects were recorded for the “Combination” group, the “Paracetamol” group, and the “Ibuprofen low dose” group. In the Ibuprofen High Dose group, however, two likely side effects were recorded, both related to stomach upset.
    The graphs of FIGS. 1 and 2 surprisingly show that the “combination” compared to “Ibuprofen High Dosage” brings about an essentially equivalent or better pain relief, especially when one considers that the “combination” only includes half the amount of ibuprofen. It is also surprising that the graphs show that the “Combination” provides significantly better pain relief than “Ibuprofen Low Dosage” because both medications contained the same amount of ibuprofen and the paracetamol in the “Combination” would not be expected to patients who are already taking 1,200 mg ibuprofen per day would bring additional relief.
    While an effective alleviation of symptoms due to osteoarthritis can already be achieved in the first dose interval (2 tablets as described above), it is preferred to continue thereafter with an administration schedule in four doses per day. Two tablets or capsules four times a day makes a relatively simple dosage schedule for a user. Increasing from this amount could lead to dosage and administration problems. This is an additional benefit beyond the potential for reducing negative side effects.
    The tablets or capsules listed above can be prepared and presented in the same manner as described in published patent specification WO 2006/004 449 by AFT Pharmaceuticals, the contents of which are incorporated herein by reference.
    Alternative chemical forms
    While in the present document reference is made in particular to ibuprofen and paracetamol, other suitable pharmaceutically acceptable forms of the two active ingredients (eg salts etc.) can be used, the parts by weight having to be adjusted accordingly, and these other forms apply by reference the active ingredients themselves are also included in the protection area. For example, if a salt form is used in the formulation, a sufficient amount must be taken into account to achieve the desired amount of acid (e.g. 342 mg ibuprofen lysinate corresponds to 200 mg ibuprofen). Thus, for example, a reference to 150 mg ibuprofen is also to be understood as a reference to the therapeutically equivalent amount of ibuprofen lysinate.
    While some preferred embodiments of the invention have been described herein, purely by way of example, it is clear that modifications and improvements can be made without departing from the scope of the following patent claims.
    权利要求:
    Claims (12)
    [1]
    Use of paracetamol and ibuprofen for the manufacture of a medicament for the treatment of moderate or severe osteoarthritis or moderate or severe rheumatoid arthritis, which medicament comprises a combination composition with ibuprofen and paracetamol for administration of 250 mg to 300 mg ibuprofen and 950 mg to 1000 mg Paracetamol per dosage.
    [2]
    2. Use according to claim 1, wherein the medicament is for the treatment of moderate or severe osteoarthritis.
    [3]
    Use according to claim 1 wherein the medicament is for the treatment of moderate or severe rheumatoid arthritis.
    [4]
    4. Use according to claim 1, 2 or 3, wherein the medicament is divided into dosage units with from 125 mg to 150 mg ibuprofen and from 475 mg to 500 mg paracetamol for administration of two dosage units per dosage.
    [5]
    Use according to claim 1, 2 or 3, wherein each dosage unit contains 150 mg ibuprofen and 500 mg paracetamol.
    [6]
    Use according to any one of the preceding claims wherein the medicament is for use in two dosage units up to four times a day.
    [7]
    Use according to any one of the preceding claims, wherein the medicament is intended to be taken in two dosage units four times a day.
    [8]
    8. Use according to claim 6 or 7, wherein the dosage units are tablets or capsules.
    [9]
    Use according to claim 1 wherein the medicament is for the delivery of 300 mg ibuprofen and 1000 mg paracetamol per dosage.
    [10]
    Use according to claim 1 wherein the medicament is for the delivery of 300 mg ibuprofen and 1000 mg paracetamol per dose up to 4 times a day.
    [11]
    Use according to any one of the preceding claims, wherein the composition is in the form of at least one solid dosage unit.
    [12]
    12. Use according to claim 1, 2 or 3, wherein the composition is in liquid form.
    类似技术:
    公开号 | 公开日 | 专利标题
    DE69629184T2|2004-05-06|USE OF VITAMIN D2 OR VITAMIN D4 DERIVATIVES FOR PRODUCING A MEDICINAL PRODUCT FOR TREATING SECONDARY HYPERPARATHYROIDISM
    US6689399B1|2004-02-10|Transdermal delivery of an anti-inflammatory composition
    DE10197266T5|2005-05-12|Procedures for local anesthesia and pain relief
    CH702339B1|2016-06-15|Combination of paracetamol and ibuprofen to treat osteoarthritis.
    EP2222292A2|2010-09-01|Novel use of omega-3-fatty acid|
    DE60132008T2|2008-12-11|CYTYLMYRISTATE AND CETYLPALMITATE FOR THE TREATMENT OF ECCEMENTS AND / OR PSORIASIS
    EP0037488B1|1984-09-19|Pharmaceutical composition for healing inflammatory and/or degenerative and/or atrophic mucous membranes
    DE102008036725B4|2021-01-28|Pharmaceutical composition for nasal application
    EP1001756B1|2004-04-07|Synergistically acting compositions for selectively combating tumor tissue
    EP2367546B1|2013-05-08|Combination of local anesthetic and analgesic for relieving breast pain
    DE10163667B4|2006-10-26|Use of deoxypeganine for the treatment of clinical depression
    EP0820771A2|1998-01-28|Pharmaceutical compositions for the treatment of neuropathies containing a lipid-soluble thiamine and a magnesium compound
    EP2120918B1|2010-03-31|Pharmaceutical composition for treating incontinence
    DE102020106962B4|2022-03-03|Combination drug for antipsychotic therapy
    DE2831728C2|1982-12-23|Medicines used to treat headaches
    DE102018111140A1|2019-01-24|Pharmaceutical product for use in tumor therapy
    EP0720854A1|1996-07-10|Use of bile acids for the preparation of a medicament for the treatment of skin disorders
    DE3419686A1|1984-11-29|Use of a composition with therapeutic activity
    DE202008000655U1|2009-02-26|Composition for the treatment of ailments and diseases of the muscles and joints
    DE3923088A1|1991-01-24|Combination anti-rheumatic compsns. - contg. dapson and non-steroidal antiinflammatory agent
    DE4116400A1|1992-11-19|Injection solns. contg. non-steroidal antiphlogistic substances - for local treatment of acute, sub-acute and chronic recidivist pains of rheumatic or non-rheumatic origin
    DE2105024B|Sleeping pills
    DE2220500B2|1980-06-19|analgesic
    AT500999A1|2006-05-15|TOLPERISONE CONTAINING VETERINARY MEDICINE PREPARATION FOR ORAL ADMINISTRATION IN THE TREATMENT OF MAMMALS, SUCH AS DOGS WITH DEGENERATIVE, SPINAL SYMPTOMS
    DE202011110392U1|2014-01-16|Orally administrable pharmaceutical composition for the treatment of menstrual pain accompanied by excessive menstrual blood loss
    同族专利:
    公开号 | 公开日
    KR20110112279A|2011-10-12|
    RU2487707C2|2013-07-20|
    TR201906742T4|2019-05-21|
    AU2009304002B2|2013-04-18|
    CL2011000678A1|2011-09-23|
    LT2341900T|2019-04-10|
    AU2009304002A1|2010-04-22|
    MX2011003928A|2011-08-12|
    WO2010044681A1|2010-04-22|
    PL2341900T3|2019-08-30|
    EP2341900B1|2019-02-20|
    JP2012505830A|2012-03-08|
    CN102215835A|2011-10-12|
    ES2725151T3|2019-09-19|
    BRPI0914086A2|2020-01-21|
    HUE043063T2|2019-07-29|
    US20110166234A1|2011-07-07|
    DK2341900T3|2019-05-20|
    CA2735834A1|2010-04-22|
    MA32635B1|2011-09-01|
    MX340662B|2016-07-20|
    GB2476418B|2013-04-24|
    TR201102810T2|2011-05-23|
    ZA201101752B|2012-02-29|
    CO6341553A2|2011-11-21|
    AU2009304002B9|2014-06-26|
    EP2341900A4|2012-02-29|
    EP2341900A1|2011-07-13|
    MY153932A|2015-04-15|
    CA2735834C|2017-05-16|
    SI2341900T1|2019-06-28|
    GB201105249D0|2011-05-11|
    GB2476418A|2011-06-22|
    NZ591496A|2012-12-21|
    RU2011111792A|2012-11-27|
    PT2341900T|2019-05-14|
    HRP20190891T1|2019-07-12|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    ZA837556B|1982-11-15|1984-06-27|Upjohn Co|Acetominophen and ibuprofen/flurbiprofen|
    EP0109281A1|1982-11-15|1984-05-23|The Upjohn Company|Compositions comprising flurbiprofen or ibuprofen|
    AU605538B2|1988-01-19|1991-01-17|Adcock Ingram Limited|Pharmaceutical unit|
    CA1336687C|1989-08-23|1995-08-15|Thomas M. Tencza|Process for preparing tablets containing ibuprofen,apap and caffeine, the products of this process andthe use of such products|
    CA2570474C|2004-07-07|2010-01-05|Aft Pharmaceuticals Limited|A combination composition comprising paracetamol and ibuprofen|
    GB0519350D0|2005-09-22|2005-11-02|Boots Healthcare Int Ltd|Therapeutic agents|
    US20090264530A1|2008-04-16|2009-10-22|Nickell Robert P|Combined nsaid and acetaminophen formulation and method|CA2570474C|2004-07-07|2010-01-05|Aft Pharmaceuticals Limited|A combination composition comprising paracetamol and ibuprofen|
    CN107519159A|2010-11-04|2017-12-29|阿福特药物有限公司|Compound|
    WO2016008546A1|2014-07-18|2016-01-21|Everbright Pharmaceuticals S.A.R.L.|Aqueous formulation comprising paracetamol and ibuprofen|
    AU2018300075A1|2017-07-10|2020-01-30|Gel Cap Technologies, LLC|Dual release dosage form capsule and methods, devices and systems for making same|
    US11197830B2|2019-02-27|2021-12-14|Aft Pharmaceuticals Limited|Pharmaceutical composition containing acetaminophen and ibuprofen|
    法律状态:
    2014-03-14| NV| New agent|Representative=s name: WAGNER PATENT AG, CH |
    优先权:
    申请号 | 申请日 | 专利标题
    NZ56961208|2008-10-14|
    PCT/NZ2009/000220|WO2010044681A1|2008-10-14|2009-10-12|A medicinal product and treatment|
    [返回顶部]