CN102740843A - Combination of theobromine with a decongestant and its use for the treatment of cough - Google Patents

Combination of theobromine with a decongestant and its use for the treatment of cough Download PDF

Info

Publication number
CN102740843A
CN102740843A CN2010800570306A CN201080057030A CN102740843A CN 102740843 A CN102740843 A CN 102740843A CN 2010800570306 A CN2010800570306 A CN 2010800570306A CN 201080057030 A CN201080057030 A CN 201080057030A CN 102740843 A CN102740843 A CN 102740843A
Authority
CN
China
Prior art keywords
agent
cough
theobromine
combination
reagent
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN2010800570306A
Other languages
Chinese (zh)
Inventor
约翰·布鲁
罗宾·马克·班尼斯特尔
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Reyes Leather Co.,Ltd. Ethiopia Lancome
Infirst Healthcare Ltd
Original Assignee
Biocopea Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biocopea Ltd filed Critical Biocopea Ltd
Publication of CN102740843A publication Critical patent/CN102740843A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • 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
    • 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
    • A61K31/33—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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/14—Antitussive agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Emergency Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

An agent comprises theobromine and a decongestant, as a combined preparation for simultaneous, sequential or separate use in therapy, particularly in the therapy of cough.

Description

Theobromine with separate the combination of congested agent and be used to treat the purposes of cough
Technical field
The present invention relates to drug regimen, its compositions with and in treatment, special purposes in treatment of cough.
Background technology
Cough is a kind of guarding reflex.Persistent cough maybe troublesome.Can use over-the-counter drug, but its effectiveness can't be confirmed.
WO98/42322 discloses the purposes that theobromine that oral way uses is used to treat cough.
People FASEB J.express article 10.1096 such as Usmeni disclose theobromine to be suppressed the sensory nerve effect and suppresses cough.Action effect in following situation after the clear oral administration of tables of data is provided: the cough that citric acid causes in to Cavia porcellus and to the mankind in capsaicin cough challenge, and after the independent Cavia porcellus sympathetic nerve preparation of taking a shower.
Shown already that understanding congested agent pseudoephedrine induced and have very limited effectiveness in the cough model people J Pharmacol Sci such as (, 2006) Minamizawa at the citric acid of Cavia porcellus.Yet most of documents fail all to prove that pseudoephedrine has the antitussive effect.The influence (this has very little meaning at field of medicaments) to " cough and flu " described in most of articles, but do not have one piece of article to describe perhaps even check direct antitussive effect.
Summary of the invention
The present invention is at least partly based on showing theobromine and the data that citric acid is induced the collaborative antitussive effect in the cough model that are combined in of separating congested agent pseudoephedrine.This tables of data is clear, when theobromine during with the pseudoephedrine combination, its effect shockingly effective and compare with the summation of drug alone higher, this disclosed this combination have very big improvement effect.In view of confirming that not pseudoephedrine has the antitussive effect, so this point is surprising especially.
As a result, two kinds of medicines that significantly reduce dosage can be used for obtaining the effects equivalent for every kind of drug alone, thereby have reduced side effect and drug burden.
Therefore, according to a first aspect of the invention, a kind of reagent comprises theobromine and conciliates congested agent, as the combination preparation of in treatment, using simultaneously, order is used or used respectively.
According to a second aspect of the invention, pharmaceutical composition comprises theobromine and conciliates congested agent.
Can believe that all are separated congested agent and all represent this conspiracy relation.Although do not hope to be entangled in any theory, this possibly be owing to the structural similarity between each member of medicine who separates congested class causes.
Description of drawings
Fig. 1 representes that the combination of theobromine and theobromine and pseudoephedrine induces the influence of cough to the citric acid in the Cavia porcellus.
The specific embodiment
It is one type of definite medicine well known by persons skilled in the art that the term that uses among this paper " is separated congested agent ".Preferably, separating congested agent is alpha-2-adrenoceptor antagonists.Can select the congested agent of separating of any appropriate format.These comprise salt, prodrug and active metabolite.
" treatment of cough " used among this paper means the number of times of minimizing cough and/or any treatment of the order of severity.Preferably, it means the number of times that reduces cough, promptly reduces the direct antitussive effect of the cough impulsion of health.Therefore, according to preferred implementation of the present invention, a kind of reagent comprises theobromine and conciliates congested agent, and it is as the antitussive medicine compositions.Reagent of the present invention can be as anti-tussive agents in the control of cough.Preferably, it is used to control dry cough.
Separate the amount that congested agent can become known for its application and use, but combination according to the present invention means that the dosage of minimizing possibly be effective.The dosage of using with theobromine of separating congested agent depends on conventional factor (comprising its effectiveness) certainly, but it is preferably 0.1mg/kg/ days at least, for example at least 5mg/kg/ days, and can be up to 50mg/kg/ days.Preferably, separating congested agent uses with the dosage in 0.1mg/kg/ days to 30mg/kg/ days the scope.
Can select the theobromine of any appropriate format.These comprise salt, prodrug and active metabolite.Theobromine can also be cocoa or chocolate form.The suitable dosage range of theobromine is well known in the art, and it depends on conventional factor (age etc.), but the cooperative effect of this combination means and can reduce effective dose.
Can be used for combined administration, use simultaneously or use in proper order with single preparation or with two kinds of independent preparation forms according to combination of the present invention.
Thisly separate congested agent and be preferably selected from following medicine: ephedrine, levmetamfetamine (levmetamfetamine), naphazoline, oxymetazoline, phenylephrine (phenylephrine), phenylpropanolamine, propylhexedrine (propylhexedrine), pseudoephedrine, Synephrine (synephrine) and tetrahydrozoline.More preferably, separating congested agent is pseudoephedrine.
Chemical compound of the present invention can use in any suitable manner, such as via mouth approach, inhalation route, intranasal approach, Sublingual approach, intravenous route, rectum approach and vaginal approach.
Chemical compound of the present invention preferably is used for oral combination, but for example as tablet, lozenge, lozenge, aqueous or oiliness suspending agent dispersed powders or granule.Preferred pharmaceutical compositions of the present invention is tablet and capsule.Being used for oral liquid dispersant can be syrup, emulsion and suspension.More preferably, pharmaceutical composition of the present invention is compressed tablets or the capsule with conventional excipients, and the example is as follows.
Being intended to be used for oral compositions can be according to the known any means preparation in the manufacturing field of pharmaceutical composition, and such compositions can comprise one or more reagent that are selected from sweeting agent, flavoring agent, coloring agent and antiseptic and see exquisite good to eat preparation to provide from the pharmacy angle.Tablet comprises the active agent and the mixture that is applicable to the pharmaceutically acceptable excipient of non-toxicity of making tablet of combination.These excipient can for example comprise inert diluent, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; Granulating agent and disintegrating agent, for example corn starch or alginic acid; Binding agent, for example starch gel, arabic gum, microcrystalline Cellulose or polyvinyl pyrrolidone; And lubricant, for example magnesium stearate, stearic acid or Talcum.Tablet can be not coated, and perhaps they can pass through the known technology coating with disintegrate and the absorption of delay in gastrointestinal tract, thereby the continuous action of longer time is provided.For example can use time-delay material such as glycerol monostearate or glyceryl distearate.
Waterborne suspension can comprise the active material of combination and be suitable for preparing the mixture of the excipient of waterborne suspension.Such excipient is a suspending agent, for example sodium carboxymethyl cellulose, methylcellulose, hydroxypropyl emthylcellulose, sodium alginate, polyvinyl pyrrolidone, Tragacanth and arabic gum; Dispersion or wetting agent can be naturally occurring phospholipid; Lecithin for example, perhaps condensation product of the condensation product of epoxyalkane and fatty acid (for example Myrj 45) or oxirane and long chain aliphatic (for example heptadecyl ethylidene oxygen spermol (Heptadecaethyleneoxycetanol)) or oxirane and derive from the condensation product (for example polyoxyethylene sorbitan monoleate) of the part ester of fatty acid.Waterborne suspension can also comprise one or more antiseptic (for example P-hydroxybenzoic acid ethyl ester or n-pro-pyl ester), one or more coloring agent, one or more flavoring agents and one or more sweeting agents (such as sucrose and glucide).
Oily suspensions can be prepared through following mode: active component is suspended in the vegetable oil (for example Oleum Arachidis hypogaeae semen, olive oil, Oleum sesami or Oleum Cocois); Be suspended in the polyethylene glycol hydrogenated Oleum Ricini; Be suspended in the fatty acid (for example oleic acid); Perhaps be suspended in mineral oil (for example liquid paraffin), perhaps be suspended in other surfactants or the detergent (detergents).Oily suspensions can comprise thickening agent, such as Cera Flava, hard paraffin or spermol.Can add sweeting agent (such as above those that mention) and flavoring agent so that good to eat oral formulations to be provided.Can keep these compositionss through adding antioxidant (such as ascorbic acid).
But through in dispersed powders that is suitable for preparing waterborne suspension and granule, adding water active component that obtains to make up and the mixture that disperses reagent or moistening reagent, suspending agent and one or more antiseptic.Can also there be suitable sweeting agent, flavoring agent and coloring agent.
The pharmaceutical composition of combination of the present invention can also be the O/w emulsion form.Oil phase can be vegetable oil (for example olive oil or an Oleum Arachidis hypogaeae semen), or mineral oil (for example liquid paraffin), or these mixture.Suitable emulsifying agent can be naturally occurring glue class, for example arabic gum or Tragacanth; Naturally occurring phospholipid, for example Semen sojae atricolor, lecithin; With by fatty acid and deutero-ester of hexitol or part ester, for example sorbitan monoleate; With the condensation product of said part ester and oxirane, for example polyoxyethylene sorbitan monoleate.Said emulsion can also comprise sweeting agent and flavoring agent.
Syrup and elixir can for example glycerin, propylene glycol, Sorbitol or sucrose be prepared with sweeting agent.Above-mentioned preparation can also comprise demulcent (demulcent), antiseptic, flavoring agent and coloring agent.
Suspension and emulsion can comprise supporting agent, for example natural gum, agar, sodium alginate, pectin, methylcellulose, carboxymethyl cellulose or polyvinyl alcohol.
Can utilize conventional preparation technique production according to the compositions of combination of the present invention.Particularly, can use spray drying to prepare microgranule, this microgranule comprises the active agent that is dispersed in or is suspended in the material that controllable release character is provided.
Can also use grinding technics (for example jet grinding) to prepare therapeutic combination.This technology specifically is applied to be intended to the granule used through suction.Fine particle can utilize routine techniques to be achieved through the manufacturing of grinding.The term that uses among this paper " grinding " is meant, can apply enough active forces to the granule of active material so that granule is broken into or wears into any mechanical technology of fine particle.Various lapping devices and condition all are applicable to produces compositions of the present invention.
For active force that required grade is provided in the suitable grinding condition limit of power that is chosen in those skilled in the art of (for example severity of grind and persistent period).Ball milling is a preferable methods.Perhaps, can use high-pressure homogenizer, wherein make and contain particulate fluid, thereby produce high shear and turbulent condition under high pressure through valve.All possibly promote particulate breaking to collision between particulate shear force, granule and machine surface or other granules and the cavitation that produces owing to fluidic acceleration.
Suitable homogenizer comprises EmulsiFlex high-pressure homogenizer, Niro Soavi high-pressure homogenizer and Microfluidics Microfluidiser.Can use grinding technics obtain the to have above-mentioned mass median aerodynamic diameter microgranule of (mass median aerodynamic diameters).If the active agent moisture absorption can adopt above-mentioned hydrophobic material to grind so.
If desired, can prepare with extra excipient then through the microgranule of grinding steps production.This can be through for example CO-spray-drying realization of drying process with atomizing.In this embodiment, granule can be suspended in the solvent, and with the solution or the suspension CO-spray-drying of additional excipients.Preferred additional excipients comprises polysaccharide.Can also use the effective excipient of extra pharmacy.
Be intended to be used to suck application, topical application, intranasal application, Sublingual application, intravenous applications, rectum is used and the compositions of the combination of vaginal application can be made the known any means preparation in field according to pharmaceutical composition.
Can carry out with common known mode according to treatment of the present invention, this depends on various factors, comprises sex, age or patient's the patient's condition, and exist or other one or more follow treatment.Patient crowd possibly be important.
The present invention is at least partly based on following research.
Research
Design a research and investigated cough is induced in the combination of the pseudoephedrine of theobromine and two kinds of various dose to the citric acid in the clear-headed conscious Cavia porcellus antitussive activity.
Proof load
1. vehicle Control
2. theobromine (10mg/kg.p.o.)
Theobromine (10mg/kg, p.o.)+pseudoephedrine (10mg/kg.p.o.)
Theobromine (10mg/kg, p.o.)+pseudoephedrine (30mg/kg.p.o.)
Method
In whole research, use male Dunkin Hartley Cavia porcellus (400-500g is provided by Harlan UK Ltd).
Encode (blinding code) with any one in 30 Cavia porcellus random assortment to four treatment group according to blind method., record just discloses blind method coding after having measured the coughs of all animals to the investigator.
Cavia porcellus exposes 2 hours before at citric acid and takes theobromine (dose volume 2mL/kg) via the oral mode of raising by force.Pseudoephedrine exposes preceding 30 minutes at citric acid to be taken, and control animal exposes preceding 2 hours and takes carrier 30 minutes the time at citric acid.
Each Cavia porcellus, citric acid is placed exposure chamber with 2L/min air-flow before exposing during t-10min so that it shakes down.When t=0min, cause the cough response through being exposed in the citric acid aerosol (1M) that produces with the spray rate of 0.6mL/min by ultrasonic aerosolizer 10 minutes.
Write down whole 10 minutes in the citric acid process-exposed the cough number and expose back 5 minutes cough number.
The result
Result of study shown, (10mg/kg, pretreat p.o.) cause the quantity of the inductive cough of citric acid significantly to reduce (13 ± 3) (referring to Fig. 1) and coughing fit time significant prolongation (156 ± 15s) (data not shown goes out) for the first time to adopt theobromine.With pseudoephedrine (10mg/kg and 30mg/kg) combination, theobromine as far as the inhibition response of the inductive cough behavior of citric acid just the sum (9 ± 2c.f.13 ± 3) of cough (Fig. 1) and for the first time (170 ± 15s c.f.156 ± 15s) (data not shown goes out) aspect all has been enhanced along with maximum dose level the coughing fit time.

Claims (6)

1. one kind comprises the reagent that theobromine is conciliate congested agent, and it is as the combination preparation of in treatment, using simultaneously, order is used or used respectively.
2. according to the reagent of claim 1, wherein said treatment is to cough.
3. pharmaceutical composition, it comprises theobromine and conciliates congested agent.
4. according to reagent any one in the aforementioned claim or compositions, wherein saidly separate congested agent and be selected from ephedrine, levmetamfetamine, naphazoline, oxymetazoline, phenylephrine, phenylpropanolamine, propylhexedrine, pseudoephedrine, Synephrine and tetrahydrozoline.
5. according to the reagent or the compositions of claim 4, wherein said to separate congested agent be pseudoephedrine.
6. according to reagent any one in the aforementioned claim or compositions, wherein saidly separate congested agent and use with 0.1 to 30mg/kg/ day dosage.
CN2010800570306A 2009-12-14 2010-12-14 Combination of theobromine with a decongestant and its use for the treatment of cough Pending CN102740843A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB0921805.8A GB0921805D0 (en) 2009-12-14 2009-12-14 Drug composition and its use in therapy
GB0921805.8 2009-12-14
PCT/GB2010/052085 WO2011073646A1 (en) 2009-12-14 2010-12-14 Combination of theobromine with a decongestant and its use for the treatment of cough

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN201610214436.XA Division CN105816462A (en) 2009-12-14 2010-12-14 Drug combination with theobromine and its use in therapy

Publications (1)

Publication Number Publication Date
CN102740843A true CN102740843A (en) 2012-10-17

Family

ID=41667045

Family Applications (2)

Application Number Title Priority Date Filing Date
CN2010800570306A Pending CN102740843A (en) 2009-12-14 2010-12-14 Combination of theobromine with a decongestant and its use for the treatment of cough
CN201610214436.XA Pending CN105816462A (en) 2009-12-14 2010-12-14 Drug combination with theobromine and its use in therapy

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN201610214436.XA Pending CN105816462A (en) 2009-12-14 2010-12-14 Drug combination with theobromine and its use in therapy

Country Status (18)

Country Link
EP (1) EP2512464A1 (en)
JP (2) JP2013513651A (en)
CN (2) CN102740843A (en)
AU (1) AU2010332494B2 (en)
BR (1) BR112012014161A2 (en)
CA (1) CA2784214C (en)
CO (1) CO6541630A2 (en)
EC (1) ECSP12012132A (en)
GB (1) GB0921805D0 (en)
IL (1) IL220383A (en)
MX (1) MX343222B (en)
NZ (1) NZ600243A (en)
PE (1) PE20121537A1 (en)
RU (1) RU2564904C2 (en)
SG (2) SG181686A1 (en)
UA (1) UA105944C2 (en)
WO (1) WO2011073646A1 (en)
ZA (1) ZA201204293B (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10016437B2 (en) 2009-06-16 2018-07-10 Infirst Healthcare Limited Drug combinations and uses in treating a coughing condition
GB0910375D0 (en) 2009-06-16 2009-07-29 Biocopea Ltd Drug composition and its use in therapy
GB201111485D0 (en) * 2011-07-05 2011-08-17 Biocopea Ltd Drug composition and its use in therapy
US9314465B2 (en) 2009-06-16 2016-04-19 Infirst Healthcare Limited Drug combinations and uses in treating a coughing condition
US9308211B2 (en) 2009-06-16 2016-04-12 Infirst Healthcare Limited Drug combinations and uses in treating a coughing condition

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040202677A1 (en) * 2003-04-10 2004-10-14 Hopkins Kevin J. Method of enhanced regional body fat reduction
CN101024014A (en) * 2007-03-16 2007-08-29 邓丽菊 Medicine composition for treating cough and asthma

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1130354A (en) * 1993-09-07 1996-09-04 普罗克特和廿保尔公司 Compositions containing amino acid salt of propionic acid non-steroidal anti-inflammatory agent and at least one of decongestant an expectorant, an antihistamine and an antitussive
HUP9700654A2 (en) 1997-03-26 1999-09-28 Dezső Korbonits Antitussive compositions containing theobromine
US6417206B1 (en) * 2001-01-26 2002-07-09 Medpointe Healthcare Inc. Antitussive/antihist aminic/decongestant compositions
JP2002308761A (en) * 2001-04-09 2002-10-23 Taisho Pharmaceut Co Ltd Antitussive agent for common cold
JP2003128549A (en) * 2001-08-15 2003-05-08 Rohto Pharmaceut Co Ltd Composition applicable to mucous membrane
JP4377564B2 (en) * 2002-05-02 2009-12-02 ロート製薬株式会社 Composition for internal use
RU2311919C2 (en) * 2002-12-30 2007-12-10 Каунсел Оф Сайнтифик Энд Индастриал Рисерч Development of anti-coughing and throat softening herbal composition
US20060153926A1 (en) * 2005-01-10 2006-07-13 Bascom Charles C Compositions, products and methods for controlling weight in a mammal
US20080003280A1 (en) * 2006-06-26 2008-01-03 Levine Brian M Combination cough treatment compounds and method of treating common coughs
KR20080009994A (en) * 2006-07-25 2008-01-30 안국약품 주식회사 Compositions for treating of cough

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040202677A1 (en) * 2003-04-10 2004-10-14 Hopkins Kevin J. Method of enhanced regional body fat reduction
CN101024014A (en) * 2007-03-16 2007-08-29 邓丽菊 Medicine composition for treating cough and asthma

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MINAMIZAWA K 等: ""Effect of d-Pseudoephedrine on Cough Reflex and Its Mode of Action in Guinea Pigs", 《JOURNAL OF PHARMACOLOGICAL SCIENCES》 *
USMANI OS 等: "Theobromine inhibits sensory nerve activation and cough", 《THE FASEB JOURNAL》 *

Also Published As

Publication number Publication date
BR112012014161A2 (en) 2016-05-17
SG10201408377QA (en) 2015-02-27
CO6541630A2 (en) 2012-10-16
MX343222B (en) 2016-10-28
ECSP12012132A (en) 2012-09-28
PE20121537A1 (en) 2012-12-21
AU2010332494B2 (en) 2015-01-15
IL220383A0 (en) 2012-08-30
JP2016040279A (en) 2016-03-24
JP2013513651A (en) 2013-04-22
CN105816462A (en) 2016-08-03
SG181686A1 (en) 2012-07-30
WO2011073646A1 (en) 2011-06-23
NZ600243A (en) 2013-07-26
UA105944C2 (en) 2014-07-10
CA2784214A1 (en) 2011-06-23
AU2010332494A1 (en) 2012-06-14
RU2564904C2 (en) 2015-10-10
ZA201204293B (en) 2013-02-27
MX2012006625A (en) 2012-10-05
RU2012129839A (en) 2014-01-27
CA2784214C (en) 2018-01-09
EP2512464A1 (en) 2012-10-24
IL220383A (en) 2017-01-31
GB0921805D0 (en) 2010-01-27

Similar Documents

Publication Publication Date Title
JP6078605B2 (en) A therapeutic combination of theobromine and antihistamines
JP6118919B2 (en) Drug combination with theobromine and its use in therapy
CN102740843A (en) Combination of theobromine with a decongestant and its use for the treatment of cough
AU2011294905B2 (en) Theobromine in combination with an expectorant or a mucolytic for use in therapy
JP2016041748A (en) Drug combination with theobromine and use thereof in therapy
AU2015200654B2 (en) Combination of theobromine with a decongestant and its use for the treatment of cough
AU2015201844B2 (en) Therapeutic Combinations of Theobromine and an Antihistamine
AU2015201845B2 (en) Drug combination with theobromine and its use in therapy
AU2015200651B2 (en) Theobromine in combination with an expectorant or a mucolytic for use in therapy

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
ASS Succession or assignment of patent right

Owner name: THE FIRST MEDICAL HEALTH CARE CO., LTD.

Free format text: FORMER OWNER: RUISI PIKOU PIYA CO., LTD.

Effective date: 20141210

Owner name: RUISI PIKOU PIYA CO., LTD.

Free format text: FORMER OWNER: BIOCOPEA LTD.

Effective date: 20141210

C41 Transfer of patent application or patent right or utility model
TA01 Transfer of patent application right

Effective date of registration: 20141210

Address after: London, England

Applicant after: InFirst Healthcare Ltd.

Address before: Dublin, Ireland

Applicant before: Reyes Leather Co.,Ltd. Ethiopia Lancome

Effective date of registration: 20141210

Address after: Dublin, Ireland

Applicant after: Reyes Leather Co.,Ltd. Ethiopia Lancome

Address before: London, England

Applicant before: BIOCOPEA Ltd.

RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20121017