WO1997019680A1 - Therapeutical use of beta-mimetic agents for the transmucosal treatment of dysmenorrhoea - Google Patents
Therapeutical use of beta-mimetic agents for the transmucosal treatment of dysmenorrhoea Download PDFInfo
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- WO1997019680A1 WO1997019680A1 PCT/FR1995/001566 FR9501566W WO9719680A1 WO 1997019680 A1 WO1997019680 A1 WO 1997019680A1 FR 9501566 W FR9501566 W FR 9501566W WO 9719680 A1 WO9719680 A1 WO 9719680A1
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- WIPO (PCT)
- Prior art keywords
- agent
- mimetic
- new use
- use according
- mimetic agent
- Prior art date
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- 206010013935 Dysmenorrhoea Diseases 0.000 title abstract description 11
- 230000001225 therapeutic effect Effects 0.000 title abstract description 7
- 230000003454 betamimetic effect Effects 0.000 title description 3
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 39
- 239000003814 drug Substances 0.000 claims abstract description 19
- 229940079593 drug Drugs 0.000 claims abstract description 9
- 229940121363 anti-inflammatory agent Drugs 0.000 claims abstract description 4
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 4
- 239000003416 antiarrhythmic agent Substances 0.000 claims abstract description 3
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 3
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 3
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 17
- 229960002052 salbutamol Drugs 0.000 claims description 15
- 208000005171 Dysmenorrhea Diseases 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 11
- 210000004400 mucous membrane Anatomy 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims description 4
- 229960000195 terbutaline Drugs 0.000 claims description 4
- 229960004620 bitolterol Drugs 0.000 claims description 3
- FZGVEKPRDOIXJY-UHFFFAOYSA-N bitolterol Chemical compound C1=CC(C)=CC=C1C(=O)OC1=CC=C(C(O)CNC(C)(C)C)C=C1OC(=O)C1=CC=C(C)C=C1 FZGVEKPRDOIXJY-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 210000004877 mucosa Anatomy 0.000 claims description 3
- -1 pirbutol Chemical compound 0.000 claims description 3
- YREYLAVBNPACJM-UHFFFAOYSA-N 2-(tert-butylamino)-1-(2-chlorophenyl)ethanol Chemical compound CC(C)(C)NCC(O)C1=CC=CC=C1Cl YREYLAVBNPACJM-UHFFFAOYSA-N 0.000 claims description 2
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 claims description 2
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 claims description 2
- 239000002876 beta blocker Substances 0.000 claims description 2
- 229940097320 beta blocking agent Drugs 0.000 claims description 2
- 239000006172 buffering agent Substances 0.000 claims description 2
- 229950004306 colterol Drugs 0.000 claims description 2
- PHSMOUBHYUFTDM-UHFFFAOYSA-N colterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(O)=C1 PHSMOUBHYUFTDM-UHFFFAOYSA-N 0.000 claims description 2
- 239000008139 complexing agent Substances 0.000 claims description 2
- 229960001022 fenoterol Drugs 0.000 claims description 2
- JSJCTEKTBOKRST-UHFFFAOYSA-N mabuterol Chemical compound CC(C)(C)NCC(O)C1=CC(Cl)=C(N)C(C(F)(F)F)=C1 JSJCTEKTBOKRST-UHFFFAOYSA-N 0.000 claims description 2
- 229950004407 mabuterol Drugs 0.000 claims description 2
- 229960004017 salmeterol Drugs 0.000 claims description 2
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- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000002921 anti-spasmodic effect Effects 0.000 description 2
- 229960003060 bambuterol Drugs 0.000 description 2
- ANZXOIAKUNOVQU-UHFFFAOYSA-N bambuterol Chemical compound CN(C)C(=O)OC1=CC(OC(=O)N(C)C)=CC(C(O)CNC(C)(C)C)=C1 ANZXOIAKUNOVQU-UHFFFAOYSA-N 0.000 description 2
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 2
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- 239000000812 cholinergic antagonist Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
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- 230000002685 pulmonary effect Effects 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 229960001634 ritodrine Drugs 0.000 description 2
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- KQXKVJAGOJTNJS-UHFFFAOYSA-N 1-(tert-butylamino)-3-(2-cyclopentylphenoxy)propan-2-ol Chemical compound CC(C)(C)NCC(O)COC1=CC=CC=C1C1CCCC1 KQXKVJAGOJTNJS-UHFFFAOYSA-N 0.000 description 1
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000002881 Colic Diseases 0.000 description 1
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- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010029216 Nervousness Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 206010065347 Premenstrual pain Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 206010046809 Uterine pain Diseases 0.000 description 1
- STGOXRVTUNXXLQ-UHFFFAOYSA-N [2-hydroxy-2-(4-nitrophenyl)ethyl]-propan-2-ylazanium;chloride Chemical compound Cl.CC(C)NCC(O)C1=CC=C([N+]([O-])=O)C=C1 STGOXRVTUNXXLQ-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
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- 208000005298 acute pain Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000808 adrenergic beta-agonist Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
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- 229940124748 beta 2 agonist Drugs 0.000 description 1
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- 229960001631 carbomer Drugs 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 230000003749 cleanliness Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 150000003997 cyclic ketones Chemical class 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BDLIUDMKOFUDEO-UHFFFAOYSA-L disodium;[(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)-methylamino]methanesulfonate;3-methylbutyl 2-[2-(diethylamino)ethylamino]-2-phenylacetate Chemical compound [Na+].[Na+].O=C1C(N(CS([O-])(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1.O=C1C(N(CS([O-])(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1.CCN(CC)CCNC(C(=O)OCCC(C)C)C1=CC=CC=C1 BDLIUDMKOFUDEO-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960001650 glafenine Drugs 0.000 description 1
- GWOFUCIGLDBNKM-UHFFFAOYSA-N glafenine Chemical compound OCC(O)COC(=O)C1=CC=CC=C1NC1=CC=NC2=CC(Cl)=CC=C12 GWOFUCIGLDBNKM-UHFFFAOYSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
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- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 229960001632 labetalol Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 230000001670 myorelaxant effect Effects 0.000 description 1
- 229940100652 nasal gel Drugs 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
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Classifications
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
-
- 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
Definitions
- betamimetic medicament intended for the treatment or the relief of gynecological disorders by administration by the mucosal route.
- the invention relates in particular to the use of betamimetics agents for the production of a medicament intended for the treatment or relief of dysmenorrhea or algomenorrhea, characterized in that said ⁇ -mimetic agent is administered in one of the forms which are suitable for one of the n mucous membranes and, in particular, for the pernasal
- the new route of administration of ⁇ -mimetic agents makes it possible to produce a drug intended to suppress or reduce menstrual pain without any troublesome or undesirable cardiac or pulmonary effect.
- the mucous membrane includes the application of the drug to one of the accessible mucous membranes for therapeutic treatment and in particular the nasal mucosa and the sublingual mucosa.
- peripheral analgesics such as pyramido ⁇ glafenine and above all noramidopy ⁇ ne as well as non-steroidal anti-inflammatory drugs, inhibitors of prostaglandin synthesis and usual mode of treatment of dysmenorrhea
- non-steroidal anti-inflammatory drugs inhibitors of prostaglandin synthesis and usual mode of treatment of dysmenorrhea
- myo-relaxants such as racefemme, which can sometimes lead to insomnia and psychotonic actions.
- ⁇ -mimetic agents are conventionally divided into ⁇ -1 mimetic agents and into ⁇ -2 mimetic agents according to whether they stimulate the cardiac adrenergic receptors ( ⁇ -1 agents) or the pulmonary adrenergic receptors ( ⁇ -2 agents mimetics). Not all ⁇ -mimetic agents are necessarily selective and may act preferentially either on the ⁇ -1 receptors. either on the ⁇ -2 receptors. without being inactive on receptors of the other type. They can also be partial agonists of the ⁇ - 1 and ⁇ -2 receptors This is why, it is possible to add to the ⁇ -mimetic agents, compounds of the ⁇ -blocker type which have, in addition, an intrinsic action, activating more or less pronounced on the ⁇ receptors.
- ⁇ -mimetic agents some are specific for ⁇ -2 receptors, others have a more general action on ⁇ receptors.
- terbutaline which is a selective ⁇ -2 mimetic agent and which acts essentially on bronchial receptors
- albuterol which is as selective as terbutaline and whose pharmacological properties and known therapeutic indications, are similar to those of terbutaline, the isoethane whose degree of selectivity is slightly lower, penbuterol whose ⁇ -2 agonist activity is relatively selective, bitolterol and its sets, which constitutes a pro-drug of another ⁇ -mimetic agent colterol, 0 bambuterol which is a chemical derivative of salbutamol of which it has substantially the pharmacological properties , fenoterol, ritodrine, salmeterol, tulobuterol, mabuterol and GR-6341 1.
- the object of the present invention is therefore a medicament which suppresses the painful phenomena of the menstrual period without causing neither hormonal phenomena nor effects on the central nervous system and whose effectiveness is rapid and constant. This could be achieved by using for this therapeutic purpose, a ⁇ -mimetic agent and mainly one of those mentioned above, administered by the mucosa and especially by the pernasal route. 0
- anti-dysmenorrhea drugs have no central effects like conventional analgesics and have no influence on the course of the menstrual period.
- the pharmaceutical forms contain from 0.1 to 10 mg of a ⁇ -mimetic agent administered from one to three times a day during the menstrual period.
- a ⁇ -mimetic agent administered from one to three times a day during the menstrual period.
- the preference will go to active principles of longer duration of action. long like bambuterol or bitolterol and so it will be possible to reduce the number of doses
- salbutamol although its action is shorter, has the advantage of greater speed of action and thus results in faster relief.
- the medicaments according to the invention are administered in one of the forms suitable for mucosal administration.
- solutions or suspensions propelled by an inert propellant gas and gels to be applied to the nasal mucosa Preferably, a solution or suspension intended for the pernasal route is used, administered under propellant gas pressure or under ambient air pressure.
- the content of active principle will range from 0.2 to 5 mg per unit intake.
- the dosage depends on the intensity of the pain, the speed of action of the active ingredient, the duration of its action and the route of administration
- the medicaments according to the invention contain, in addition, one or more inert excipients or vehicles, non-toxic, suitable for the abovementioned route of administration.
- adhesion agents such as modified or unmodified celluloses may be mentioned. , lactose, sorbitol, palatinite, carbonates or phosphates of alkaline earth metals or magnesium, fatty substances, polar solvents which allow or facilitate the passage of mucous membranes such as cyclic ketones, cyclic lactams, bile acids and their hydrogenated derivatives.
- the medicament according to the invention finds a therapeutic use for the attenuation of primary dysmenorrhea, secondary dysmenorrhea consecutive to a trauma, an inflammation or an infection of the appendages 15 and also in the case of endomet ⁇ osis at least as an adjuvant of the usual treatment, especially hormonal.
- the ⁇ -mimetic agent can be added with an anti-arrhythmic or bradicardizing agent such as quinidine or an anti-inflammatory agent such as Mefenamic acid or Flufenamic acid.
- an anti-arrhythmic or bradicardizing agent such as quinidine
- an anti-inflammatory agent such as Mefenamic acid or Flufenamic acid.
- the solute is supplemented with isotonic substances such as mineral salts, anti-bacterial substances which guarantee microbial cleanliness, complexing agents, buffering substances or even reducing substances.
- isotonic substances such as mineral salts, anti-bacterial substances which guarantee microbial cleanliness, complexing agents, buffering substances or even reducing substances.
- the nasal gel is preferably formed from a very viscous aqueous solution or dispersion of Carbomer and in particular of acrylic polymer sold under the brand Carbopol.
- the medicament according to the invention can also be in the form of tablets intended to be placed under the tongue and to dissolve on contact with saliva.
- the sample size is 15.
Landscapes
- Health & Medical Sciences (AREA)
- Emergency Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A novel therapeutical use of β-mimetic agents for preparing a drug suitable for treating or alleviating dysmenorrhoea is disclosed. The pharmaceutical forms used contain 0.1-10 mg of a β-mimetic agent combined with one or more non-toxic inert excipients or carriers suitable for transmucosal delivery. The β-mimetic agent may be combined with an antiarrhythmic agent, a bradycardiac agent or an anti-inflammatory agent.
Description
Uti l i sati on thérapeuti que d ' agents betamimeti ques pour trai ter l es doul eurs men struel l es par voi e permuqueuse Therapeutic use of betamimetric agents to treat menstrual pain by pus
La présente invention se rapporte au domaine de la thérapeutique et plus 5 particulièrement au domaine de la thérapeutique gynécologiqueThe present invention relates to the field of therapy and more particularly to the field of gynecological therapy
Elle a plus précisément pour objet une nouvelle utilisation d'un médicament bêtamimetique destiné au traitement ou au soulagement des troubles gynécologiques par administration par voie permuqueuseMore specifically, it relates to a new use of a betamimetic medicament intended for the treatment or the relief of gynecological disorders by administration by the mucosal route.
1010
L'invention concerne en particulier l'utilisation des agents betamimetiques en vue de la réalisation d'un médicament destiné au traitement ou au soulagement des dysménorrhées ou algoménorrhées, caractérise en ce que ledit agent β-mimétique est administre sous une des formes qui conviennent pour l'une des voies n permuqueuse et, en particulier, pour la voie pernasaleThe invention relates in particular to the use of betamimetics agents for the production of a medicament intended for the treatment or relief of dysmenorrhea or algomenorrhea, characterized in that said β-mimetic agent is administered in one of the forms which are suitable for one of the n mucous membranes and, in particular, for the pernasal
La nouvelle voie d'administration des agents β-mimétiques permet de réaliser un médicament destiné à supprimer ou à réduire les douleurs menstruelles sans effet cardiaque ou pulmonaire gênant ou indésirableThe new route of administration of β-mimetic agents makes it possible to produce a drug intended to suppress or reduce menstrual pain without any troublesome or undesirable cardiac or pulmonary effect.
2020
La voie permuqueuse inclut l'application du médicament sur une des muqueuses accessibles pour un traitement thérapeutique et notamment la muqueuse nasale et la muqueuse sublinguale.The mucous membrane includes the application of the drug to one of the accessible mucous membranes for therapeutic treatment and in particular the nasal mucosa and the sublingual mucosa.
2* On sait depuis très longtemps, que la survenue des règles s'accompagne soit au préalable d'une période de tension, de nervosité ou de congestion plus ou moins douloureuse qui est. habituellement, traitée par des agents anti-inflammatoires, car liés à la montée du niveau des prostaglandiπes soit surtout de douleurs plus ou moins aiguës au moment de l'apparition des règles, et qui sont liées a une2 * We have known for a very long time that the onset of menstruation is accompanied beforehand by a period of tension, nervousness or more or less painful congestion which is. usually, treated with anti-inflammatory agents, because linked to the rise in the level of prostaglandiπes is mainly pain more or less acute at the time of menstruation, and which are linked to a
M) hypercontractibilité de la muqueuse utérine A une époque plus ancienne, beaucoup de femmes, au moment des règles, étaient obligées de rester allongées ou devaient prendre des médicaments antalgiques dont l'efficacité n'a pas pu être prouvéeM ) hypercontractibility of the uterine lining In an older era, many women, during menstruation, were forced to lie down or had to take painkillers whose effectiveness could not be proven
L'emploi des antalgiques périphériques comme le pyramidoπ la glafenine et surtout 15 la noramidopyπne ainsi que des anti-inflammatoires non stéroïdiens, inhibiteurs de la synthèse des prostaglandines et mode de traitement habituel des dysménorrhées, n'est pas ans inconvénient, ni sans risque pour la santé De même, l'utilisation de spasmolytiques végétaux ou de synthèse est d'action transitoire et rapidement
inefficace. On a également préconisé l'usage de myo-relaxants comme la racefémme, qui peuvent entraîner parfois des insomnies et des actions psychotoniques.The use of peripheral analgesics such as pyramidoπ glafenine and above all noramidopyπne as well as non-steroidal anti-inflammatory drugs, inhibitors of prostaglandin synthesis and usual mode of treatment of dysmenorrhea, is not without disadvantage, nor without risk for health Similarly, the use of plant or synthetic spasmolytics has a transient and rapid action ineffective. We also recommended the use of myo-relaxants such as racefemme, which can sometimes lead to insomnia and psychotonic actions.
Mais surtout, un article de M. DELECOUR (Sem. Hôp. Paris 1984 - 60) fait ressortir le fait que les β-mimétiques (Ritodrine ou salbutamol) amenaient des effets secondaires gênants, comme des palpitations et des tremblements et surtout ne convenaient pas pour les sujets à contre-indication habituelle des β-mimétiques (cardiopathies, asthme, diabète).But above all, an article by M. DELECOUR (Sem. Hôpital. Paris 1984 - 60) highlights the fact that β-mimetics (Ritodrine or salbutamol) bring on bothersome side effects, such as palpitations and tremors and above all are not suitable. for subjects with the usual contraindication of β-mimetics (heart disease, asthma, diabetes).
Toutes ces thérapeutiques symptomatiques ont été trouvées comme agissant sur les douleurs au moment où elles surviennent, mais l'effet est transitoire et après le succès, l'algoménorrhée peut récidiver, beaucoup plus intense.All these symptomatic therapies have been found to act on pain when they occur, but the effect is transient and after success, the algomenorrhea can recur, much more intense.
De même, le traitement hormonal de ces syndromes comporte un certain nombre de risques vasculaires et métaboliques. II est souvent la cause d'intolérances ou de problèmes cutanés.Similarly, the hormonal treatment of these syndromes involves a number of vascular and metabolic risks. It is often the cause of intolerance or skin problems.
Faute de médicament efficace et durable, il était préférable, pour les sujets dysmenorrheiques, que cette période se passe au repos et même en position allongée.In the absence of an effective and lasting drug, it was preferable, for dysmenorrheic subjects, that this period be spent at rest and even in the lying position.
La vie active que mènent beaucoup de femmes, à l'heure actuelle, et les impératifs du travail, sont incompatibles avec un tel type de contrainte. II était donc nécessaire, pour un certain nombre de femmes, qui tous les mois, au moment de la période menstruelle, connaissaient des périodes particulièrement douloureuses, d'accepter de connaître trois ou quatre journées où elles devront endurer des douleurs utérines prononcées, soit d'utiliser un médicament efficace et sans effet secondaire, qui leur permette de surmonter cette période douloureuse, ou mieux encore, de voir disparaître cette période.The active life that many women lead today and the imperatives of work are incompatible with this type of constraint. It was therefore necessary, for a certain number of women, who every month, at the time of the menstrual period, experiencing particularly painful periods, to accept to know three or four days when they will have to endure pronounced uterine pain, either d '' use an effective drug without side effects, which allows them to overcome this painful period, or better yet, to see this period disappear.
II est connu que les agents β-mimétiques sont classiquement repartis en agents β- 1 mimétiques et en agents β-2 mimétiques selon qu'ils stimulent les récepteurs adrénergiques cardiaques (agents β-1 ) ou les récepteur adréπergiques pulmonaires (agents β-2 mimétiques). Tous les agents β-mimétiques ne sont pas nécessairement sélectifs et peuvent mter agir préfentiellement soit sur les récepteurs β-1 . soit sur les récepteurs β-2. sans pour cela être inactifs sur les récepteurs de l'autre type. Ils peuvent aussi être des agonistes partiels des récepteurs β- 1 et β-2
C'est pourquoi, on peut ajouter aux agents β-mimétiques, des composes du type β- bloqueur qui possèdent, en plus, une action intrinsèque, activante plus ou moins prononcée sur les récepteurs β. Un exemple de ces agonistes du type mixte est en 5 particulier un β-2 bloqueur comme le Labetalol ou l'INPEA Ces composés possèdent donc une action β-2 stimulante en plus de leur action β-2 bloquante, occasionnant un certain ralentissement du rythme cardiaque, propre aux β-2 bloqueurs. On constate néanmoins, qu'ils provoquent les effets propres aux agents β-mimétiques tout en étant plus limités.It is known that β-mimetic agents are conventionally divided into β-1 mimetic agents and into β-2 mimetic agents according to whether they stimulate the cardiac adrenergic receptors (β-1 agents) or the pulmonary adrenergic receptors (β-2 agents mimetics). Not all β-mimetic agents are necessarily selective and may act preferentially either on the β-1 receptors. either on the β-2 receptors. without being inactive on receptors of the other type. They can also be partial agonists of the β- 1 and β-2 receptors This is why, it is possible to add to the β-mimetic agents, compounds of the β-blocker type which have, in addition, an intrinsic action, activating more or less pronounced on the β receptors. An example of these mixed type agonists is in particular a blocking β-2 such as Labetalol or INPEA These compounds therefore have a stimulating β-2 action in addition to their blocking β-2 action, causing a certain slowing of the rhythm cardiac, specific to β-2 blockers. However, it is found that they cause the effects specific to β-mimetic agents while being more limited.
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II existe, de ce fait, une grande variété d'agents β-mimétiques, les uns sont spécifiques des récepteurs β-2, d'autres ont une action plus générale sur les récepteurs β. C'est ainsi que l'on peut citer la terbutaline qui est un agent β-2 mimétique sélectif et qui agit essentiellement sur les récepteurs bronchiques,There is, therefore, a wide variety of β-mimetic agents, some are specific for β-2 receptors, others have a more general action on β receptors. Thus we can cite terbutaline which is a selective β-2 mimetic agent and which acts essentially on bronchial receptors,
15 l'albutérol (salbutamol) qui est aussi sélectif que la terbutaline et dont les propriétés pharmacologiques et les indications thérapeutiques connues, sont similaires à celles de la terbutaline, l'isoéthaπne dont le degré de sélectivité est un peu moindre, le penbutérol dont l'activité β-2 agoniste est relativement sélective, le bitoltérol et ses sets, qui constitue une pro-drug d'un autre agent β-mimétique le coltérol, le 0 bambuterol qui est un dérivé chimique du salbutamol dont il possède sensiblement les propriétés pharmacologiques, le fénotérol, la ritodrine, le salmétérol, le tulobutérol, le mabutérol et le GR-6341 1 .15 albuterol (salbutamol), which is as selective as terbutaline and whose pharmacological properties and known therapeutic indications, are similar to those of terbutaline, the isoethane whose degree of selectivity is slightly lower, penbuterol whose β-2 agonist activity is relatively selective, bitolterol and its sets, which constitutes a pro-drug of another β-mimetic agent colterol, 0 bambuterol which is a chemical derivative of salbutamol of which it has substantially the pharmacological properties , fenoterol, ritodrine, salmeterol, tulobuterol, mabuterol and GR-6341 1.
L'objet de la présente invention est donc un médicament qui supprime les 5 phénomènes douloureux de la période menstruelle sans entraîner ni phénomènes hormonaux, ni effets sur le système nerveux central et dont l'efficacité est rapide et constante. Ceci a pu être réalisé en employant pour ce but thérapeutique, un agent β-mimétique et principalement un de ceux mentionnés précédemment, administré par voie permuqueuse et surtout par voie pernasale. 0The object of the present invention is therefore a medicament which suppresses the painful phenomena of the menstrual period without causing neither hormonal phenomena nor effects on the central nervous system and whose effectiveness is rapid and constant. This could be achieved by using for this therapeutic purpose, a β-mimetic agent and mainly one of those mentioned above, administered by the mucosa and especially by the pernasal route. 0
De ce fait, les médicaments anti-dysménorrhée n'ont pas d'effets centraux comme les antalgiques classiques et n'ont pas d'influence sur le déroulement de la période menstruelle.As a result, anti-dysmenorrhea drugs have no central effects like conventional analgesics and have no influence on the course of the menstrual period.
Î > Selon l'invention, les formes pharmaceutiques renferment de 0, 1 a 10 mg d'un agent β-mimétique administre de une a trois fois par jour pendant la période menstruelle La préférence ira à des principes actifs de durée d'action plus longue comme le bambuterol ou le bitoltérol et ainsi, il sera possible de réduire le nombre de prises
quotidiennes Cependant, le salbutamol bien que son action soit un p>eu plus courte compone l'avantage d'une rapidité d'action plus grande et entraîne ainsi, un soulagement plus rapideÎ> According to the invention, the pharmaceutical forms contain from 0.1 to 10 mg of a β-mimetic agent administered from one to three times a day during the menstrual period. The preference will go to active principles of longer duration of action. long like bambuterol or bitolterol and so it will be possible to reduce the number of doses However, salbutamol, although its action is shorter, has the advantage of greater speed of action and thus results in faster relief.
Des essais réalises a partir d'un agent β-mimétique et notamment du salbutamol, ont d'ailleurs montré la rapidité et l'efficacité d'action de ces médicaments Testé sur des patientes qui ressentaient la douleur aiguë typique des algoménorrhées, l'administration permuqueuse (ou sub-lmguale) de 200 pg de médicament a conduit aux résultats suivants .Tests carried out using a β-mimetic agent and in particular salbutamol, have moreover shown the speed and effectiveness of the action of these drugs Tested on patients who felt the acute pain typical of algomenorrhea, the administration permuqueuse (or sub-lmguale) of 200 pg of drug led to the following results.
• en ce qui concerne les patientes qui n'avaient pris aucun traitement préalable, la réduction des douleurs s'élève en moyenne à 42%, 10 mn après l'administration et à 57%, 20mn après cette même prise pour la quasi totalité des patientes.• in the case of patients who had not taken any prior treatment, the reduction in pain amounted on average to 42%, 10 minutes after administration and to 57%, 20 minutes after this same intake for almost all of the patients.
Remarque : il serait peut-être intéressant d'obtenir les résultats engendrés par un traitement classique seul (anti-inflammatoire, antalgique et/ou anti-spasmodique non b-mimétique) afin de pouvoir comparer les résultats avec ceux de la seule administration de salbutamol.Note: it would perhaps be interesting to obtain the results generated by a conventional treatment alone (anti-inflammatory, analgesic and / or anti-spasmodic non-b-mimetic) in order to be able to compare the results with those of the only administration of salbutamol .
• pour ce qui est des essais effectués sur des patientes qui avaient eu recours, préalablement à l'administration de salbutamol, à un autre traitement (antalgique, anti-inflammatoire et/ou anti-spasmodique, autres qu'un agent β-mimétique), mais qu'elles avaient jugé insuffisamment efficace, l'amélioration ressentie est en moyenne de l'ordre de 56% dès les 10 mn suivant la prise, et de 79%, 20 mn après cette même prise. Dans ce dernier cas, la performance obtenue tant au niveau de la rapidité que de l'efficacité du soulagement de la douleur, laisse supposer très vraisemblablement une synergie.• with regard to tests carried out on patients who had used, before the administration of salbutamol, another treatment (analgesic, anti-inflammatory and / or anti-spasmodic, other than a β-mimetic agent) , but that they considered insufficiently effective, the improvement felt is on average around 56% from the 10 minutes after taking it, and 79%, 20 minutes after this same taking. In the latter case, the performance obtained both in terms of the speed and effectiveness of pain relief, most likely suggests synergy.
Les médicaments selon l'invention sont administrés sous une des formes convenant pour l'administration permuqueuse. On pourra citer à cet égard, les solutions ou suspensions propulsées par un gaz propulseur inerte et les gels à appliquer sur la muqueuse nasale. D'une manière préférée, on utilise une solution ou suspension destinée à la voie pernasale, administrée sous pression de gaz propulseur ou sous pression de l'air ambiant.The medicaments according to the invention are administered in one of the forms suitable for mucosal administration. In this regard, mention may be made of solutions or suspensions propelled by an inert propellant gas and gels to be applied to the nasal mucosa. Preferably, a solution or suspension intended for the pernasal route is used, administered under propellant gas pressure or under ambient air pressure.
D'une manière préférée, la teneur en principe actif s'échelonnera de 0,2 à 5 mg par prise unitaire. La posologie dépend de l'intensité des douleurs, de la rapidité
d'action du principe actif, de la durée d'action de celui-ci et de la voie d'administrationIn a preferred manner, the content of active principle will range from 0.2 to 5 mg per unit intake. The dosage depends on the intensity of the pain, the speed of action of the active ingredient, the duration of its action and the route of administration
Les médicaments selon l'invention contiennent, en outre, un ou plusieurs excipients s ou véhicules inertes, non-toxiques, appropriés pour la voie d'administration précitée On pourra citer à cet égard, les agents d'adhésion comme les celluloses modifiées ou non, le lactose, le sorbitol, la palatinite, les carbonates ou phosphates de métaux alcalmo-terreux ou de magnésium, les corps gras, les solvants polaires qui permettent ou facilitent le passage permuqueux comme les cétones cycliques, les 10 lactames cycliques, les acides biliaires et leurs dérivés hydrogénés.The medicaments according to the invention contain, in addition, one or more inert excipients or vehicles, non-toxic, suitable for the abovementioned route of administration. In this regard, adhesion agents such as modified or unmodified celluloses may be mentioned. , lactose, sorbitol, palatinite, carbonates or phosphates of alkaline earth metals or magnesium, fatty substances, polar solvents which allow or facilitate the passage of mucous membranes such as cyclic ketones, cyclic lactams, bile acids and their hydrogenated derivatives.
Le médicament selon l'invention trouve un emploi en thérapeutique pour l'atténuation des dysménorrhées primaires, des dysménorrhées secondaires consécutives à un traumatisme, à une inflammation ou à une infection des annexes 15 et également dans le cas d'endométπose au moins comme adjuvant du traitement habituel, notamment hormonal.The medicament according to the invention finds a therapeutic use for the attenuation of primary dysmenorrhea, secondary dysmenorrhea consecutive to a trauma, an inflammation or an infection of the appendages 15 and also in the case of endometπosis at least as an adjuvant of the usual treatment, especially hormonal.
L'agent β-mimétique peut être additionné d'un agent anti-arythmique ou bradicardisant comme la quinidine ou d'un agent anti-inflammatoire comme l'acide 20 Mefenamique ou l'acide Flufenamique.The β-mimetic agent can be added with an anti-arrhythmic or bradicardizing agent such as quinidine or an anti-inflammatory agent such as Mefenamic acid or Flufenamic acid.
Le soluté est additionné de substances isotonisantes comme des sels minéraux, de substances anti-bactériennes qui garantissent la propreté microbienne, d'agents complexants, de substances tampons ou bien encore, de substances réductrices.The solute is supplemented with isotonic substances such as mineral salts, anti-bacterial substances which guarantee microbial cleanliness, complexing agents, buffering substances or even reducing substances.
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Le gel nasal est formé de préférence d'une solution ou dispersion aqueuse très visqueuse de Carbomère et notamment, de polymère acrylique commercialisé sous la marque Carbopol.The nasal gel is preferably formed from a very viscous aqueous solution or dispersion of Carbomer and in particular of acrylic polymer sold under the brand Carbopol.
M) Le médicament selon l'invention peut également se présenter sous forme de comprimés destinés à être placés sous la langue et se dissoudre au contact de la salive.M ) The medicament according to the invention can also be in the form of tablets intended to be placed under the tongue and to dissolve on contact with saliva.
OBSERVATIONS CLINIQUES ι> Résumé et PrésentationCLINICAL OBSERVATIONS ι> Summary and Presentation
Effet du salbutamol en administration sublinguale dans le traitement des dysménorrhées
La présente observation est le résultat d'une collection de visites effectuées en "urgence". II n'y a pas eu de tirage au sort et ce n'est pas une étude randomisée.Effect of salbutamol in sublingual administration in the treatment of dysmenorrhea This observation is the result of a collection of "emergency" visits. There was no draw and it is not a randomized study.
L'efficacité du salbutamol en spray (deux bouffées, soit 200 microgrammes de salbutamol) n'est envisagée que par rapport au traitement qui précède la visite ou à défaut, par rapport à lui-même La patiente côte sur un segment de droite l'amélioration subjective qu'elle ressent. Aucune échelle visuelle n'a été utilisée.The efficacy of salbutamol spray (two puffs, i.e. 200 micrograms of salbutamol) is only considered in relation to the treatment preceding the visit or, failing this, in relation to itself The patient coast on a segment of the right subjective improvement she feels. No visual scale was used.
La taille de l'échantillon est de 15.The sample size is 15.
Ont été incluses, toutes les patientes qui ressentaient une douleur typique de colliques utérines, soit par la description académique qu'elles en faisaient, soit par la ressemblance évidente avec leurs douleurs pré-menstruelles habituelles.Were included, all patients who experienced pain typical of uterine colic, either by the academic description they made of it, or by the obvious resemblance to their usual pre-menstrual pain.
9 patientes sur 15 ont été spectaculairement améliorées à 20 mn par rapport à leur traitement habituel pris avant.9 out of 15 patients were dramatically improved at 20 minutes compared to their usual treatment taken before.
4 patientes qui n'avaient rien pris avant l'administration de ventoline connaissent une amélioration non négligeable.4 patients who had taken nothing before the administration of ventoline experienced a significant improvement.
• 2 échecs se révèlent réfractaires également à tout traitement classique. Un échec est imputable à une crise d'angoisse.• 2 failures are also refractory to any conventional treatment. Failure is due to an anxiety attack.
Lorsque la patiente n'a pris aucun traitement avant l'arrivée du médecin, les résultats restent honorables (effet à 20 mn supérieur a 50% en moyenne), tout en étant moindres. On peut imaginer que le traitement classique est synergique de celui qui a été effectué.When the patient did not take any treatment before the arrival of the doctor, the results remain honorable (effect at 20 min greater than 50% on average), while being less. One can imagine that the classic treatment is synergistic to that which was carried out.
9 patientes sur 15 sont spectaculairement améliorées par une prise standard de deux bouffées de salbutamol sublinguales, alors qu'elles avaient deja eu recours a un autre traitement avant la venue du médecin9 out of 15 patients are dramatically improved by a standard intake of two puffs of salbutamol sublingual, whereas they had already used another treatment before the doctor came
L'une des patientes est peu améliorée au bout de 10 mn et retourne ensuite quasiment à son état initial (10% d'amélioration seulement). Elle présentait, en fait, des signes de crise aigue d'angoisse qui faussaient probablement l'appréciation de la douleurOne of the patients improved little after 10 min and then returned almost to its initial state (only 10% improvement). She was, in fact, showing signs of an acute anxiety attack which probably distorted the appreciation of the pain
Le plus mauvais score est obtenu chez une patiente qui restera refractaire a tout traitement (voir plus loin)The worst score is obtained in a patient who will remain refractory to any treatment (see below)
Les 2 autres patientes sont néanmoins soulagées de 40% de leur douleur au bout de 20 mnThe other 2 patients are nevertheless relieved by 40% of their pain after 20 minutes
Un cas est intéressant au titre que l'administration de salbutamol comme l'injection IV d'AvafortanR sont restées inefficaces (0%) et que seule l'injection IV de ValιumR s'est révélée salutaire Un autre cas montre que si le traitement testé s'est révélé inefficace (30% et 10% à 20 mn), le traitement classique n'a pu faire mieux One case is interesting in that the administration of salbutamol like the IV injection of Avafortan R remained ineffective (0%) and that only the IV injection of Valιum R was found to be beneficial Another case shows that if the treatment tested proved ineffective (30% and 10% at 20 min), conventional treatment could not do better
CONCLUSIONSCONCLUSIONS
Sur le petit nombre de cas d'observation, les échecs du traitement sont fortement corrélés à la présence de symptômes d'anxiété physique aigue.On the small number of cases of observation, treatment failures are strongly correlated with the presence of symptoms of acute physical anxiety.
Dans 9 cas sur 15, on observe une amélioration évidente de la douleur par rapport au traitement habituel pris avant la venue du médecin et l'administration de salbutamol sublinguale.In 9 out of 15 cases, there is an obvious improvement in pain compared to the usual treatment taken before the doctor's visit and the administration of sublingual salbutamol.
Ces résultats suggèrent fortement que le Salbutamol en administration permuqueuse à petites doses est efficace pour traiter valablement des dysménorrhées et ceci en l'absence d'effets indésirables dans cette étude.
These results strongly suggest that Salbutamol in a low dose administration of mucosal agents is effective in treating dysmenorrhea validly, and this in the absence of undesirable effects in this study.
Claims
1. Nouvelle utilisation d'un agent β-mimétique en vue de la production d'un médicament réduisant ou supprimant les douleurs menstruelles, caractérisée en ce qu'elle comporte ledit agent β-mimétique, en association ou en mélange, avec un véhicule ou un excipient inerte approprié pour la voie d'administration permuqueuse.1. New use of a β-mimetic agent for the production of a medicament reducing or eliminating menstrual pain, characterized in that it comprises said β-mimetic agent, in combination or in mixture, with a vehicle or an inert excipient suitable for the route of administration of the mucosa.
2. Nouvelle utilisation d'un agent β-mimétique pour la production d'un médicament réduisant ou supprimant les douleurs menstruelles, a base d'un agent β- mimétique selon la revendication 1 °, caractérisée en ce que le principe actif est associé ou mélangé avec un véhicule ou un excipient inerte approprié pour la voie d'administration pernasale.2. New use of a β-mimetic agent for the production of a drug reducing or eliminating menstrual pain, based on a β-mimetic agent according to claim 1, characterized in that the active principle is associated or mixed with an inert vehicle or excipient suitable for the pernasal route of administration.
3. Nouvelle utilisation selon la revendication 1 ° dans laquelle le médicament renferme une quantité efficace d'un agent β-mimétique pour amener la sédation ou la disparition des douleurs menstruelles.3. New use according to claim 1 in which the medicament contains an effective amount of a β-mimetic agent to bring about sedation or the disappearance of menstrual pain.
4. Nouvelle utilisation selon la revendication 1 ° ou la revendication 2° dans laquelle la quantité efficace d'un agent β-mimétique s'échelonne de 0, 1 à 10 mg par prise unitaire.4. New use according to claim 1 or claim 2 in which the effective amount of a β-mimetic agent ranges from 0.1 to 10 mg per unit dose.
5. Nouvelle utilisation selon l'une des revendications 1 à 3° dans laquelle la teneur en principe actif s'échelonne de préférence de 0,2 à 5 mg par prise unitaire.5. New use according to one of claims 1 to 3 ° in which the content of active principle preferably ranges from 0.2 to 5 mg per unit intake.
6. Nouvelle utilisation selon l'une des revendications 1 à 4ύ dans laquelle l'agent β-mimétique est choisi dans le groupe constitué par le salbutamol et ses esters, le pirbutérol, le bitoltérol, le coltérol, la ritodπne, la terbutaline, le fénotérol, le salmétérol, le tulobutérol, le mabutérol et le GR 6341 16. New use according to one of claims 1 to 4 ύ in which the β-mimetic agent is chosen from the group consisting of salbutamol and its esters, pirbutol, bitolterol, colterol, ritodπne, terbutaline, fenoterol, salmeterol, tulobuterol, mabuterol and GR 6341 1
7. Nouvelle utilisation selon l'une des revendications 1 à 5° dans laquelle l'agent β-mimétique est un agent β-bloqueur ayant une activité β-mimétique intrinsèque7. New use according to one of claims 1 to 5 ° in which the β-mimetic agent is a β-blocking agent having an intrinsic β-mimetic activity
8. Nouvelle utilisation selon l'une des revendications 1 à 6° dans laquelle l'agent β-mimetique est additionné d'un autre principe actif choisi dans le groupe formé d'un agent anti-arythmique, d'un agent bradycardisant et d'un agent anti- inflammatoire. 8. New use according to one of claims 1 to 6 ° in which the β-mimetic agent is added with another active principle chosen from the group formed by an anti-arrhythmic agent, a bradycardia agent and d 'an anti-inflammatory agent.
9. Nouvelle utilisation selon l'une des revendications 1 à 7° dans laquelle le médicament qui réduit ou supprime les douleurs menstruelles est formé d'un agent β-mimétique en solution ou en suspension dans un véhicule inerte non- toxique, approprié pour la voie d'administration permuqueuse ou sous forme solide.9. New use according to one of claims 1 to 7 ° in which the medicament which reduces or eliminates menstrual pain is formed of a β-mimetic agent in solution or in suspension in an inert non-toxic vehicle, suitable for the route of administration, either in the form of a mucous membrane or in solid form.
10. Nouvelle utilisation selon la revendication 8° dans laquelle la solution ou la suspension est additionnée d'un agent isotonisant et/ou d'un agent tampon et/ou d'un agent de conservation et/ou d'un agent complexant.10. New use according to claim 8 in which the solution or the suspension is added with an isotonizing agent and / or a buffering agent and / or a preservative and / or a complexing agent.
11. Nouvelle utilisation selon la revendication 8° ou la revendication 9° dans laquelle la solution ou la suspension est introduite dans un flacon hermétique dont la pression intérieure est supérieure à la pression atmosphérique. 11. New use according to claim 8 or claim 9 in which the solution or the suspension is introduced into an airtight bottle whose internal pressure is greater than atmospheric pressure.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP95941150A EP0805679A1 (en) | 1995-11-28 | 1995-11-28 | Therapeutical use of beta-mimetic agents for the transmucosal treatment of dysmenorrhoea |
PCT/FR1995/001566 WO1997019680A1 (en) | 1995-11-28 | 1995-11-28 | Therapeutical use of beta-mimetic agents for the transmucosal treatment of dysmenorrhoea |
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PCT/FR1995/001566 WO1997019680A1 (en) | 1995-11-28 | 1995-11-28 | Therapeutical use of beta-mimetic agents for the transmucosal treatment of dysmenorrhoea |
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WO1997019680A1 true WO1997019680A1 (en) | 1997-06-05 |
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PCT/FR1995/001566 WO1997019680A1 (en) | 1995-11-28 | 1995-11-28 | Therapeutical use of beta-mimetic agents for the transmucosal treatment of dysmenorrhoea |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2912654A1 (en) * | 2007-02-19 | 2008-08-22 | Rech En Toxicologie Et Pharmac | Medicament composition, useful in treating spasmodic diseases e.g. spastic colitis and dysmenorrhea, comprises phloroglucinol and paracetamol formulated together/separately for combined, simultaneous/separate use of antispasmodic therapy |
US7527614B2 (en) | 2005-03-25 | 2009-05-05 | Kimberly-Clark Worldwide, Inc. | Protective tube for a medicated tampon |
US7708726B2 (en) | 2005-04-28 | 2010-05-04 | Kimberly-Clark Worldwide, Inc. | Dosage form cap for an applicator |
US7744556B2 (en) | 2005-03-25 | 2010-06-29 | Kimberly-Clark Worldwide, Inc. | Delivery tube assembly for an applicator |
US7919453B2 (en) | 2005-03-25 | 2011-04-05 | Kimberly-Clark Worldwide, Inc. | Dosage cap assembly for an applicator |
US7993667B2 (en) | 2005-03-25 | 2011-08-09 | Kimberly-Clark Worldwide, Inc. | Methods of manufacturing a medicated tampon assembly |
Citations (4)
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EP0306422A1 (en) * | 1987-09-02 | 1989-03-08 | Medibrevex Sa | Galenical forms of 2-beta-mimetics for perlingual and sublingual administration |
WO1992002209A1 (en) * | 1990-07-31 | 1992-02-20 | Aiache Jean Marc | Method for preparing a bioadhesive galenical and galenical thereby obtained |
EP0603414A1 (en) * | 1992-07-01 | 1994-06-29 | Meiji Seika Kabushiki Kaisha | (-)-ritodrine |
FR2720276A1 (en) * | 1994-05-24 | 1995-12-01 | Christophe Boyer | Use of beta-mimetic agents e.g. salbutamol |
-
1995
- 1995-11-28 EP EP95941150A patent/EP0805679A1/en not_active Withdrawn
- 1995-11-28 WO PCT/FR1995/001566 patent/WO1997019680A1/en not_active Application Discontinuation
Patent Citations (4)
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EP0306422A1 (en) * | 1987-09-02 | 1989-03-08 | Medibrevex Sa | Galenical forms of 2-beta-mimetics for perlingual and sublingual administration |
WO1992002209A1 (en) * | 1990-07-31 | 1992-02-20 | Aiache Jean Marc | Method for preparing a bioadhesive galenical and galenical thereby obtained |
EP0603414A1 (en) * | 1992-07-01 | 1994-06-29 | Meiji Seika Kabushiki Kaisha | (-)-ritodrine |
FR2720276A1 (en) * | 1994-05-24 | 1995-12-01 | Christophe Boyer | Use of beta-mimetic agents e.g. salbutamol |
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"EFFECT OF ORCIPRENALINE AND Th 1165a (FENOTEROL) ON CONTRACTILITY OF THE HUMAN UTERUS DURING MENSTRUATION", DIALOG FILE SUPPLIER: FILE 73: EMBASE, AN=78045183, XP002009694 * |
I. BIRTALAN ET AL.: "NEW POSSIBILITIES IN THE TREAMENT OF DYSMENORRHEA", ADV. PHARMACOL. RES. PRACT., PROC. CONGR. HUNG. PHARMACOL. SOC., vol. 6, 1980, pages 167 - 172, XP002009700 * |
I.S. FRASER: "DYSMENORRHEA", CURR. THER. ENDOCRINOL. METAB., vol. 5, 1994, pages 215 - 219, XP002009696 * |
M. AKERLUND ET AL.: "EFFECTS OF TERBUTALINE ON MYOMETRIAL ACTIVITY, UTERINE BLOOD FLOW, AND LOWER ABDOMINAL PAIN IN WOMEN WITH PRIMARY DYSMENORRHOEA", BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, vol. 83, no. 9, 1976, pages 673 - 678, XP002009698 * |
M. AKERLUND: "POTENTIAL USE OF BETA-ADRENOCEPTOR AGONISTS IN GYNAECOLOGY", ACTA PHARMACOL. TOXICOL., vol. 44, no. 2, 1979, pages 93 - 100, XP002009699 * |
O. LALOS ET AL.: "EFFECT OF SALBUTAMOL ON THE NON-PREGNANT HUMAN UTERUS IN VIVO", ACTA OBSTET. GYNECOL. SCAND., vol. 60, no. 4, 1981, pages 349 - 352, XP002009697 * |
PINTO E SILVA ET AL.: "THERAPEUTIC ASSOCIATION (FENOTEROL AND IBUPROFEN) IN PRIMARY DYSMENORRHEA", JORNAL BRASILEIRO DE GINECOLOGIA, vol. 100, no. 5-6, 1990, pages 129 - 131, XP002009701 * |
R. CIFUENTES ET AL.: "INHIBITION OF MENSTRUAL UTERINE MOTILITY WITH FOUR BETA-ADRENERGIC DRUGS", REPRODCCION, vol. 5, no. 1, 1981, pages 31 - 41, XP002009695 * |
R.CIFUENTES ET AL., REV. COLOMB. OBSTET. GINEC., vol. 27, no. 4, 1976, COLOMBIA, pages 195 - 204 * |
S. KULLANDER ET AL.: "TERBUTALINE INHALATION FOR ALLEVIATION OF SEVERE PAIN IN ESSENTIAL DYSMENORRHEA", ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, vol. 60, no. 4, 1981, pages 425 - 427, XP002009693 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7527614B2 (en) | 2005-03-25 | 2009-05-05 | Kimberly-Clark Worldwide, Inc. | Protective tube for a medicated tampon |
US7744556B2 (en) | 2005-03-25 | 2010-06-29 | Kimberly-Clark Worldwide, Inc. | Delivery tube assembly for an applicator |
US7919453B2 (en) | 2005-03-25 | 2011-04-05 | Kimberly-Clark Worldwide, Inc. | Dosage cap assembly for an applicator |
US7993667B2 (en) | 2005-03-25 | 2011-08-09 | Kimberly-Clark Worldwide, Inc. | Methods of manufacturing a medicated tampon assembly |
US8388996B2 (en) | 2005-03-25 | 2013-03-05 | Kimberly-Clark Worldwide, Inc. | Methods of manufacturing a medicated tampon assembly |
US7708726B2 (en) | 2005-04-28 | 2010-05-04 | Kimberly-Clark Worldwide, Inc. | Dosage form cap for an applicator |
FR2912654A1 (en) * | 2007-02-19 | 2008-08-22 | Rech En Toxicologie Et Pharmac | Medicament composition, useful in treating spasmodic diseases e.g. spastic colitis and dysmenorrhea, comprises phloroglucinol and paracetamol formulated together/separately for combined, simultaneous/separate use of antispasmodic therapy |
WO2008113929A1 (en) * | 2007-02-19 | 2008-09-25 | Promindus (Actions Promotionnelles Dans L'industrie Et Le Commerce) | Pharmaceutical composition containing phloroglucinol and paracetamol |
US8148425B2 (en) | 2007-02-19 | 2012-04-03 | Promindus (Actions Promotionnelles Dans L'industrie Et Le Commerce) | Pharmaceutical composition containing phloroglucinol and paracetamol |
Also Published As
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