WO2012090218A1 - Synergistic effects of the combination of the specific compounds with paracetamol and their effects on various diseases - Google Patents

Synergistic effects of the combination of the specific compounds with paracetamol and their effects on various diseases Download PDF

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Publication number
WO2012090218A1
WO2012090218A1 PCT/IN2011/000867 IN2011000867W WO2012090218A1 WO 2012090218 A1 WO2012090218 A1 WO 2012090218A1 IN 2011000867 W IN2011000867 W IN 2011000867W WO 2012090218 A1 WO2012090218 A1 WO 2012090218A1
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Prior art keywords
combination
paracetamol
concentration
caffeine
synergistic effects
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PCT/IN2011/000867
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French (fr)
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WO2012090218A4 (en
Inventor
Kamlesh Rajnikant Zota
Sanjay Agrawal
Ketan Chandulal Zota
Manukant Chandulal Zota
Himanshu Muktilal Zota
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Zota Health Care Ltd
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Publication of WO2012090218A4 publication Critical patent/WO2012090218A4/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Definitions

  • the present invention is based on the combination of the specific compounds and their effects on various diseases.
  • the invention relates to safety containers for biologically active substances, in particular cytostatic agents, said container having increased or higher fracture strength and shatterproof qualities, in addition to an uncontaminated exterior.
  • the invention also relates to a method for producing said containers and to the use of a medium containing at least one polymer for decontaminating the exterior of a container that is filled with a biologically active substance, sealed and optionally labelled.
  • the present invention relates to a process for producing a solid, coated pharmaceutical composition by a melt coating process.
  • the process is adapted to provide a solid, coated pharmaceutical composition by melt coating, which has a fast release.
  • compositions, methods, systems and kits for the controlled delivery of an active agent within a polymeric network upon the binding of a molecule that decreases the structural integrity of the polymeric network at one or more micro- or nanovacuoles are provided.
  • the present invention relates to a gastric-retentive controlled release mono-matrix tablet composition, comprising: a) at least one pharmacologically active substance; b) hydrogel- forming materials consisting of polyethylene oxide and at least one component selected from poloxamers and colloidal silica; and c) a carbon dioxide-generating material.
  • the composition of the present invention floats in gastric juice and can continuously release the active substance in the stomach at a constant rate for at least 2 hours.
  • the present invention provides a pharmaceutical composition in the form of pellet wherein controlled release of pharmacologically active substances can be effected.
  • the present invention is characterized by a pharmaceutical composition for controlled release pellets, consisting es -1 sentially of: a) one or more pharmacologically active substances; b) one or more lipids having a low-melting point of less than 70°C and existing as a solid at room temperature; c) one or more hydrophilic substances; and d) one or more water-insoluble binding agents, prepared without melting the lipids.
  • composition comprising A) a solid inner layer comprising i) an active substance, and ii) one or more disintegrants/exploding agents, one of more effervescent agents or a mixture thereof, the solid inner layer being sandwiched between two outer layers Bl) and B2), each outer layer comprising iii) a substantially water soluble and/or crystalline polymer or a mixture of substantially water soluble and/or crystalline polymers, the polymer being a polyglycol in the form of one of a) a homopolymer having a MW of at least about 100,000 daltons, and b) a copolymer having a MW of at least about 2,000 daltons, or a mixture thereof, and iv) an active substance, which is the same as in said solid inner layer A), and layer A being different from layer B, the layered composition being coated with a coating C) that has at least one opening exposing at least one surface of said outer layer, the coating being substantially insoluble in and impermeable to fluids
  • compositions including a sedating antihistamine and a stimulant, and methods of use thereof.
  • the stimulant reduces the sedation caused by the antihistamine, thereby allowing potent, but sedating, antihistamines to be used effectively.
  • the present invention relates to novel compounds that are useful for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies.
  • This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies.
  • the compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of infectious diseases.
  • the subject invention concerns novel compounds that are useful as long-acting local anesthetics.
  • the compounds are N-acyl derivatives of the compound known as tetracaine.
  • An object of the present invention is the provisions of some features distinguish from others. These features are Pain management is qualitatively superior with paracetamol than with other NSAIDs drugs because paracetamol is considered to be the inhibition of cyclooxygenase (COX), and it is highly selective for COX-2. While it has analgesic and antipyretic properties comparable to those of aspirin or other NSAIDs,Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain.
  • COX cyclooxygenase
  • the tolerability profile of paracetamol is better than conventional NSAIDs and is similar to that of coxibs (with respect to ulcer incidence) because paracetamol (acetaminophen), owing to its inhibitory action on cyclooxygenase, (sometimes) the paracetamol inhibiting cyclooxygenase predominantly in the central nervous system.
  • paracetamol acts through the inhibition of the recently discovered COX-3 isoform.
  • NSAIDs for example Ibuprofen, Indomethacin and Diclofenac may cause G.I. irritation and Cardiac Risk with COX2 inhibitor.
  • This invention is mainly focused compounds, efficacy of compounds and combination of compounds. Which essential for treatment of a number of diseases. These are pain, antiinfilamation, hepatoprotective, fever thereof.
  • the present invention discloses an efficient compound, compound combination and additional mechanism of compound which has several mechanisms for treatment of a number of diseases which can be treated from paracetamol, racemethionine, caffeine, chlorpheniramine maleate and Phenylephrine in variable quantities.
  • COX-2 appears to be related to cancers and abnormal growths in the intestinal tract. COX inhibitors have been shown to reduce the occurrence of cancers and pre-cancerous growths. The inhibition of COX-2 is paramount for the anti-inflammatory and analgesic function of the selective COX-2 inhibitor celecoxib, and quite likely also for its ability to prevent the development of cancerous growth.
  • the concentration of paracetamol is 500 mg/tablet and thereof.
  • Mechanism of action is that makes paracetamol such an effective and useful medicine.
  • Paracetamol has a highly targeted action in blocking an enzyme involved in the transmission of pain.
  • Racemethionine is an important sulphur containing amino acid with multiple functions throughout the body. Its role as an antioxidant and hepatoprotector has been widely documented. It protects hepatocytes and enhances their regeneration thus improving liver function, it acts as important sulphur and methyl group donor in detoxification reactions in liver cells. Methyl group and is essential for many biochemical reactions. Methionine produces S-adenosylmethionine. (SAMe). SAMe is essential for the production of Glutathione. Racemethionine is used to make the urine more acidic. Making the urine more acidic helps to relieve skin irritation in incontinent (loss of bladder control). Racemethionine is necessary for glutathione synthesis. Glutathione plays an important role in the protection of liver cells. Glutathione (-SH) controls redox reactions and acts as an antioxidant and antitoxic substance.
  • Methionine neutralizes Hypochlorous acid, a bleach-like substance that is secreted in the painful joints during conditions like rheumatoid arthritis. Thus methionine a lleviates the inflammation that is experienced as pain.Racemethionine has an important antiinflammatory
  • racemethionine The concentration of racemethionine is 50 mg./tablet and thereof. Race Methionine acts as a glutathione precursor. The incorporation of methionine into tablets of paracetamol is useful for protecting against hepatic and renal toxicity.
  • Free Radicals A molecule which is neutral contains pair of electrons while unpaired molecules are called free radicals.
  • Oxidative stress seems to play a vital role in osteoarthritis, in the case of osteoarthritis human cartilage significantly deficient in superoxide dimutase a major free radical scavenger.
  • Caffeine may also have hepatoprotective properties. Increased caffeine consumption is associated with less severe liver injury among those at high risk for liver disease, such as those with alcoholism, obesity, or hemochromatosis.
  • Caffeine also increases the effectiveness of some drugs.
  • Many over-the-counter headache drugs include caffeine in their formula. It is also used with ergotamine in the treatment of migraine and cluster headaches as well as to overcome the drowsiness caused by antihistamines.
  • the concentration of caffeine is 15 mg. /tablet and thereof.
  • Coffee is- a complex 'blend' of a vast number of different chemicals, any of which may be responsible for its reported effects on the liver.
  • Midol In addition to the variable quantity of paracetamol and about the equivalent amount of caffeine in a cup of coffee Midol also contains a mild sedative (an antihistamine) and a mild diuretic.
  • Adenosine is a water-soluble compound of adenine and ribose; it functions to modulate the activities of nerve cells and produces a mild sedative effect when it activates certain types of adenosine receptors.
  • Caffeine competes with adenosine to bind at these receptors and counteracts the sedative effects of the adenosine. If the person stops drinking coffee, the adenosine has no competition for activating its usual receptors and may produce a sedative effect that is experienced as fatigue or drowsiness.
  • Chlorpheniramine is often combined with phenylpropanolamine to form an allergy medication with both antihistamine and decongestant properties. It's suitable compound for cough and cold .it's containing codeine and chlorpheniramine. It's a first-generation alkylamine antihistamine used in the prevention of the symptoms of allergic conditions. It is also a potentiator of opioids, allowing enhanced suppression of cough, analgesia, and other effects from a given quantity of the drug by itself. In various places in the world, cough and cold preparations containing codeine and chlorpheniramine are available.
  • the concentration of chlorphenamine maleate is 2 mg/tablet and thereof.
  • Chlorpheniramine is a histamine HI antagonist (or more correctly, an inverse histamine agonist). It competes with histamine for the normal Hi -receptor sites on effectors cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. It binds to the histamine HI receptor. These blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Absorption well absorbed in the gastrointestinal tract. Phenylephrine
  • Phenylephrine's effectiveness as a decongestant stems from its vasoconstriction of nasal blood vessels, thereby decreasing blood flow to the sinusoidal vessels, leading to decreased mucosal edema. All effective cold remedies containing phenylephrine.
  • Phenylephrine is 5 mg/tablet and thereof.
  • Phenylephrine relieves stuffy nose by constricting blood vessels in the nasal air passages. This reduces the flow of fluid out of the blood vessels and into the tissues of the air passages. Phenylephrine is used to treat runny or stuffy nose, sinus congestion, sneezing, itchy nose, itchy or watery eyes, sore throat, cough, headache, and pain or fever caused by allergies or the common cold.

Abstract

This invention is based on efficacy of compounds and combination of compounds. Which essential for treatment of a number of diseases. These are pain, antiinfilamation, hepatoprotective, fever, allergy thereof. This combination has less toxicity, it has highly hepatotoxicity. The main mechanism of action of paracetamol is considered to be the inhibition of cyclooxygenase (COX) that it is highly selective for COX-2. The concentration of paracetamol is 500mg and thereof. Racemethionine is anti-oxidant nutritional supplement to treat liver diseases caused by alcoholism including cirrhosis. It acts as important sulphur and methyl group donor in detoxification reactions in liver cells. The concentration of racemethionine is 50mg and thereof. All effective cold remedies containing phenylephrine. The concentration of Phenylephrine is 5 mg/tablet and thereof. Phenylephrine to form an allergy medication with both antihistamine and decongestant properties. Chlorphenaminemaleate is suitable compound for cough and cold.chlorphenamine maleate to form an allergy medication with both antihistamine and decongestant properties. The concentration of chlorphenaminemaleate is 2 mg/tablet and thereof. Caffeine may also have hepatoprotective properties. Increased caffeine consumption is associated with less severe liver injury among those at high risk for liver disease, such as those with alcoholism, obesity, or hemochromatosis. The concentration of caffeine is 15 mg/tablet and thereof.

Description

SYNERGISTIC EFFECTS OF THE COMBINATION OF THE SPECIFIC COMPOUNDS WITH PARACETAMOL AND THEffi EFFECTS ON VARIOUS DISEASES
FIELD OF INVENTION
The present invention is based on the combination of the specific compounds and their effects on various diseases.
PRIOR ART
In the existing system as given in US 2007/0010700 Al (patent application) wherein The invention relates to safety containers for biologically active substances, in particular cytostatic agents, said container having increased or higher fracture strength and shatterproof qualities, in addition to an uncontaminated exterior. The invention also relates to a method for producing said containers and to the use of a medium containing at least one polymer for decontaminating the exterior of a container that is filled with a biologically active substance, sealed and optionally labelled.
In the existing system as given in WO 2010/070028 Al (patent application) wherein The present invention relates to a process for producing a solid, coated pharmaceutical composition by a melt coating process. The process is adapted to provide a solid, coated pharmaceutical composition by melt coating, which has a fast release.
In the existing system as given in US 2008/0226684 Al "(patent application) wherein The present invention includes compositions, methods, systems and kits for the controlled delivery of an active agent within a polymeric network upon the binding of a molecule that decreases the structural integrity of the polymeric network at one or more micro- or nanovacuoles.
In the existing system as given in WO 2006/088305 Al (patent application) wherein The present invention relates to a gastric-retentive controlled release mono-matrix tablet composition, comprising: a) at least one pharmacologically active substance; b) hydrogel- forming materials consisting of polyethylene oxide and at least one component selected from poloxamers and colloidal silica; and c) a carbon dioxide-generating material. The composition of the present invention floats in gastric juice and can continuously release the active substance in the stomach at a constant rate for at least 2 hours.
In the existing system as given in WO 2005/123138 Al (patent application) wherein The present invention provides a pharmaceutical composition in the form of pellet wherein controlled release of pharmacologically active substances can be effected. The present invention is characterized by a pharmaceutical composition for controlled release pellets, consisting es-1 sentially of: a) one or more pharmacologically active substances; b) one or more lipids having a low-melting point of less than 70°C and existing as a solid at room temperature; c) one or more hydrophilic substances; and d) one or more water-insoluble binding agents, prepared without melting the lipids.
In the existing system as given in WO 2008/148798 A2 (patent application)/ AU 2008/258596 Al (patent application)/ US 2010/0239667 Al (patent application) wherein Layered pharmaceutical composition suitable for oral use in the treatment of diseases where absorption takes place over a large part of the gastrointestinal tract. The composition comprising A) a solid inner layer comprising i) an active substance, and ii) one or more disintegrants/exploding agents, one of more effervescent agents or a mixture thereof, the solid inner layer being sandwiched between two outer layers Bl) and B2), each outer layer comprising iii) a substantially water soluble and/or crystalline polymer or a mixture of substantially water soluble and/or crystalline polymers, the polymer being a polyglycol in the form of one of a) a homopolymer having a MW of at least about 100,000 daltons, and b) a copolymer having a MW of at least about 2,000 daltons, or a mixture thereof, and iv) an active substance, which is the same as in said solid inner layer A), and layer A being different from layer B, the layered composition being coated with a coating C) that has at least one opening exposing at least one surface of said outer layer, the coating being substantially insoluble in and impermeable to fluids and comprising a polymer, and the composition having a cylindrical form optionally with one or more tapered ends, wherein the ratio between the surface area of one end surface of the cylinder and the length of the cylinder is in a range of from 0.02 to 45 mm. In the existing system as given in US 2004/0259809 Al (patent application) wherein the present invention provides pharmaceutical compositions including a sedating antihistamine and a stimulant, and methods of use thereof. The stimulant reduces the sedation caused by the antihistamine, thereby allowing potent, but sedating, antihistamines to be used effectively.
In the existing system as given in WO 2010/029545 A2 (patent application) wherein the present invention relates to novel compounds that are useful for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of pathogen cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of infectious diseases. In the existing system as given in United States Patent 61 14344 wherein the subject invention concerns novel compounds that are useful as long-acting local anesthetics. The compounds are N-acyl derivatives of the compound known as tetracaine.
THE OBJECT OF THE INVENTION
An object of the present invention is the provisions of some features distinguish from others. These features are Pain management is qualitatively superior with paracetamol than with other NSAIDs drugs because paracetamol is considered to be the inhibition of cyclooxygenase (COX), and it is highly selective for COX-2.While it has analgesic and antipyretic properties comparable to those of aspirin or other NSAIDs,Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain.
The tolerability profile of paracetamol is better than conventional NSAIDs and is similar to that of coxibs (with respect to ulcer incidence) because paracetamol (acetaminophen), owing to its inhibitory action on cyclooxygenase, (sometimes) the paracetamol inhibiting cyclooxygenase predominantly in the central nervous system. There is some speculation that paracetamol acts through the inhibition of the recently discovered COX-3 isoform.
In the case of symptoms of PMS (premenstrual syndrome) like headaches, muscular, joint pain, stomach cramps and sore breasts. Paracetamol may relieve, but they can make fluid retention worse. The other side effects of NSAIDs for example Ibuprofen, Indomethacin and Diclofenac may cause G.I. irritation and Cardiac Risk with COX2 inhibitor.
STATEMENT OF INVENTION
This invention is mainly focused compounds, efficacy of compounds and combination of compounds. Which essential for treatment of a number of diseases. These are pain, antiinfilamation, hepatoprotective, fever thereof.
DETAILED DESCRIPTION OF THE INVENTION
The present invention discloses an efficient compound, compound combination and additional mechanism of compound which has several mechanisms for treatment of a number of diseases which can be treated from paracetamol, racemethionine, caffeine, chlorpheniramine maleate and Phenylephrine in variable quantities.
Example- Neuroblastomas, pain, hepatoprotective, fever, infilamation, allergy thereof.
Paracetamol
It is a widely used over-the-counter analgesic (pain reliever) and antipyretic (fever reducer). It is commonly used for the relief of headaches, other minor aches and pains, and is a major ingredient in numerous cold and flu remedies. The main mechanism of action of paracetamol is considered to be the inhibition of cyclooxygenase (COX), and recent findings suggest that it is highly selective for COX-2. While it has analgesic and antipyretic properties comparable to those of aspirin or other NSAIDs, its peripheral anti-inflammatory activity is usually limited by several factors, one of which is high level of peroxides present in inflammatory lesions. However, in some circumstances, even peripheral anti-inflammatory activity comparable to other NSAIDs can be observed Because of its selectivity for COX-2 it does not significantly inhibit the production of the pro-clotting thromboxanes.
Mechanism of paracetamol
• Inhibition of platelet activating factor synthesis
• Prevention of Bradykinin/Cytokine induced hyperalgesia of nerves • Scavenging of hypochlorous acid.
• Blocking of histamine release.
• Prevention of cartilage damage by inhibition of metalloprotease synthesis
• Phosphodiesterase type IV inhibition.
Neuroblastomas
Small tumors of the sympathetic nervous system (neuroblastoma) have abnormal levels of COX-2 expressed.
Cancer
COX-2 appears to be related to cancers and abnormal growths in the intestinal tract. COX inhibitors have been shown to reduce the occurrence of cancers and pre-cancerous growths. The inhibition of COX-2 is paramount for the anti-inflammatory and analgesic function of the selective COX-2 inhibitor celecoxib, and quite likely also for its ability to prevent the development of cancerous growth.
The concentration of paracetamol is 500 mg/tablet and thereof.
Mechanism of action is that makes paracetamol such an effective and useful medicine. Paracetamol has a highly targeted action in blocking an enzyme involved in the transmission of pain.
Racemethionine
It's anti-oxidant nutritional supplement to treat liver diseases caused by alcoholism including cirrhosis. Racemethionine is an important sulphur containing amino acid with multiple functions throughout the body. Its role as an antioxidant and hepatoprotector has been widely documented. It protects hepatocytes and enhances their regeneration thus improving liver function, it acts as important sulphur and methyl group donor in detoxification reactions in liver cells. Methyl group and is essential for many biochemical reactions. Methionine produces S-adenosylmethionine. (SAMe). SAMe is essential for the production of Glutathione. Racemethionine is used to make the urine more acidic. Making the urine more acidic helps to relieve skin irritation in incontinent (loss of bladder control). Racemethionine is necessary for glutathione synthesis. Glutathione plays an important role in the protection of liver cells. Glutathione (-SH) controls redox reactions and acts as an antioxidant and antitoxic substance.
Methionine neutralizes Hypochlorous acid, a bleach-like substance that is secreted in the painful joints during conditions like rheumatoid arthritis. Thus methionine a lleviates the inflammation that is experienced as pain.Racemethionine has an important antiinflammatory
property which is useful in arthritis and low back pain. It helps in the synthesis of substance t hat helps to keep the gel like cartilage that Cushions joint intact. These properties make race methionine as an important partner with NSAIDs including paracetamol.
The concentration of racemethionine is 50 mg./tablet and thereof. Race Methionine acts as a glutathione precursor. The incorporation of methionine into tablets of paracetamol is useful for protecting against hepatic and renal toxicity.
Glutathione
It's Free Radicals (A molecule which is neutral contains pair of electrons while unpaired molecules are called free radicals.)
Pain and inflammation are caused by the overproduction of free radicals. A free radical called superoxide which is involved in the inflammation of arthritis. Oxidative stress seems to play a vital role in osteoarthritis, in the case of osteoarthritis human cartilage significantly deficient in superoxide dimutase a major free radical scavenger.
Caffeine
Caffeine may also have hepatoprotective properties. Increased caffeine consumption is associated with less severe liver injury among those at high risk for liver disease, such as those with alcoholism, obesity, or hemochromatosis.
Caffeine also increases the effectiveness of some drugs. Many over-the-counter headache drugs include caffeine in their formula. It is also used with ergotamine in the treatment of migraine and cluster headaches as well as to overcome the drowsiness caused by antihistamines. The concentration of caffeine is 15 mg. /tablet and thereof.
Mechanism of caffeine is that Coffee is- a complex 'blend' of a vast number of different chemicals, any of which may be responsible for its reported effects on the liver.
In addition to the variable quantity of paracetamol and about the equivalent amount of caffeine in a cup of coffee Midol also contains a mild sedative (an antihistamine) and a mild diuretic.
The effects of caffeine are thought to occur as a result of competitive antagonism at adenosine receptors. Adenosine is a water-soluble compound of adenine and ribose; it functions to modulate the activities of nerve cells and produces a mild sedative effect when it activates certain types of adenosine receptors. Caffeine competes with adenosine to bind at these receptors and counteracts the sedative effects of the adenosine. If the person stops drinking coffee, the adenosine has no competition for activating its usual receptors and may produce a sedative effect that is experienced as fatigue or drowsiness.
Chlorpheniramine Maleate
Chlorpheniramine is often combined with phenylpropanolamine to form an allergy medication with both antihistamine and decongestant properties. It's suitable compound for cough and cold .it's containing codeine and chlorpheniramine. It's a first-generation alkylamine antihistamine used in the prevention of the symptoms of allergic conditions. It is also a potentiator of opioids, allowing enhanced suppression of cough, analgesia, and other effects from a given quantity of the drug by itself. In various places in the world, cough and cold preparations containing codeine and chlorpheniramine are available.
The concentration of chlorphenamine maleate is 2 mg/tablet and thereof.
Mechanism of chlorphenamine maleate is that Chlorpheniramine is a histamine HI antagonist (or more correctly, an inverse histamine agonist). It competes with histamine for the normal Hi -receptor sites on effectors cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. It binds to the histamine HI receptor. These blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine. Absorption well absorbed in the gastrointestinal tract. Phenylephrine
Phenylephrine's effectiveness as a decongestant stems from its vasoconstriction of nasal blood vessels, thereby decreasing blood flow to the sinusoidal vessels, leading to decreased mucosal edema. All effective cold remedies containing phenylephrine.
The concentration of Phenylephrine is 5 mg/tablet and thereof.
Mechanism of Phenylephrine is that it relieves stuffy nose by constricting blood vessels in the nasal air passages. This reduces the flow of fluid out of the blood vessels and into the tissues of the air passages. Phenylephrine is used to treat runny or stuffy nose, sinus congestion, sneezing, itchy nose, itchy or watery eyes, sore throat, cough, headache, and pain or fever caused by allergies or the common cold.

Claims

1. Synergistic effects of the combination of the specific compounds and their effects on various diseases.
2. Synergistic effects of the combination of the specific compound comprises of paracetamol, racemethionine, caffeine, chlorpheniramine maleate and Phenylephrine in variable quantities.
3. Synergistic effect of the combination of the specific compound is claimed as claim 1 wherein said these are pain, antiinfilamation, hepatoprotective, fever, allergy thereof. This combination has less toxicity, it has not hepatotoxicity property.
4. Synergistic effects of the combination of the specific compound are claimed as claim 2 wherein said the mechanism of paracetamol is that inhibition of cyclooxygenase (COX), and recent findings suggest that it is highly selective for COX-2. It's selectivity for COX-2 it does not significantly inhibit the production of the pro- clotting thromboxanes. The concentration of paracetamol is 500mg and thereof.
5. Synergistic effects of the combination of the specific compound is claimed as claim 2 wherein said Racemethionine is anti-oxidant nutritional supplement to treat liver diseases caused by alcoholism including cirrhosis. It protects hepatocytes and enhances their regeneration thus improving liver function. It acts as important sulphur and methyl group donor in detoxification reactions in liver cells. It protects hepatocytes and enhances their regeneration thus improving liver function. The concentration of racemethionine is 50mg and thereof.
6. Synergistic effects of the combination of the specific compound are claimed as claim 2 wherein said all effective cold remedies containing phenylephrine. The concentration of Phenylephrine is 5 mg/tablet and thereof. Phenylephrine to form an allergy medication with both antihistamine and decongestant properties.
7. Synergistic effects of the combination of the specific compound is claimed as claim 2 wherein said Chlorphenaminemaleate is suitable compound for cough and cold .chlorphenamine maleate to form an allergy medication with both antihistamine and decongestant properties. The concentration of chlorphenaminemaleate is 2 mg./tablet and thereof.
8. Synergistic effects of the combination of the specific compound are claimed as claim 2 wherein said Caffeine may also have hepatoprotective properties. Increased caffeine
1 consumption is associated with less severe liver injury among those at high risk for liver disease, such as those with alcoholism, obesity, or hemochromatosis. The Concentration of caffeine is 15 mgVtablet and thereof.
9. Synergistic effects of the combination of the specific compound are claimed as claim 5 wherein said Race Methionine acts as a glutathione precursor. The incorporation of methionine into tablets of paracetamol is useful for protecting against hepatic and renal toxicity.
10. Synergistic effects of the combination of the specific compound are claimed as claim 8 wherein said In addition to the variable quantity of paracetamol and about the equivalent amount of caffeine in a cup of coffee Midol also contains a mild sedative (an antihistamine) and a mild diuretic.
2
PCT/IN2011/000867 2010-12-30 2011-12-19 Synergistic effects of the combination of the specific compounds with paracetamol and their effects on various diseases WO2012090218A1 (en)

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CN108186579A (en) * 2018-02-01 2018-06-22 重庆希尔安药业有限公司 Xiao ' er Anfen Huangnamin composition grain and preparation method thereof

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