WO2020097686A1 - Compositions et leurs utilisations - Google Patents

Compositions et leurs utilisations Download PDF

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Publication number
WO2020097686A1
WO2020097686A1 PCT/AU2019/051254 AU2019051254W WO2020097686A1 WO 2020097686 A1 WO2020097686 A1 WO 2020097686A1 AU 2019051254 W AU2019051254 W AU 2019051254W WO 2020097686 A1 WO2020097686 A1 WO 2020097686A1
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Prior art keywords
composition
nasal
subject
poloxamer
week
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PCT/AU2019/051254
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English (en)
Inventor
Angel Francisco Lopez
Harshita PANT
Kwok Ho YIP
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Holman Pharmaceuticals Pty Ltd
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Priority claimed from AU2018904330A external-priority patent/AU2018904330A0/en
Application filed by Holman Pharmaceuticals Pty Ltd filed Critical Holman Pharmaceuticals Pty Ltd
Publication of WO2020097686A1 publication Critical patent/WO2020097686A1/fr

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    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • 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
    • A61P11/02—Nasal agents, e.g. decongestants

Definitions

  • Intra-polyp subcutaneous; s.c. injections of sodium cromoglycate (SCG; 50 mg/kg body weight) or saline (0.9%) commenced 1-week post-engraftment. A total of 4 weekly injections of SCG or saline were administered. Mice were sacrificed at 5 weeks post-engraftment and a sample of the nasal polyp xenograft was collected for analyses.
  • SCG sodium cromoglycate
  • saline saline
  • Figure 9 show's the size of human nasal polyp xenografts measured externally at 1, 2, 3, 4 and 5 weeks post-engraftment from mice treated with weekly s.c. injections of SCG (50mg/kg body weight), Prednisolone (1 mg/kg body weight) or saline (0.9%). The results are shown as approximate volume (external mm 3 ); mean +/- standard error mean (SEM); *p ⁇ 0.05, ***p ⁇ 0.001 (SCG or Prednisolone compared to saline controls). #p ⁇ 0.05 (SCG compared to Prednisolone).
  • Figure 14 shows the number of toluidine blue-stained mast cells in nasal polyp xenografts harvested at 5 weeks post-engraftment from mice treated with weekly s.c. injections of SCG (50mg/kg body weight), Prednisolone (Img/ ’ kg body weight) or saline (0.9%); number of mast cells per mm 2 tissue (median +/- range); *p ⁇ 0.05 for indicated comparisons.
  • FIG. 19 shows the number of mucus glands (number per mm 2 ; left panel), the % mucus gland area (centre panel) and the % mucus area (right panel) in nasal polyp xenografts harvested at 5 weeks post-engraftment from ice treated with weekly s.c. injections of SCG (50mg/kg body weight), Prednisolone (1 mg/kg body weight) or saline (0.9%); number of cells as a percentage of live cells (median +/- range).
  • Figure 24 shows the effect of SCG/Poloxamer 407, SCG/saline and prednisolone on ear swelling (mm) over a 15 w eek period; Results shown as mean -f- S.E.M.. Data were analysed using 2 way ANOVA with Bonferroni post-test; **p ⁇ 0.01 , ***p ⁇ 0.001 compared to water/ 10% pluronic control.
  • the terms“treat”,“treatment”,“treating” and the like, as used herein, also refer to any and all uses which remedy, or otherwise prevent, hinder, retard, inhibit, abrogate or reverse the recurrence of nasal polyps (e.g., following nasal polyp removal by surgery).
  • the method described herein comprises administering to a subject in need thereof a composition comprising a therapeutically effective combination of (i) cromoglycic acid, or a salt thereof, and (ii) a pharmaceutically-acceptable carrier, wherein the combination is sufficient to prevent the occurrence or recurrence of a nasal polyp in the subject.
  • the amount of cromoglycic acid or salt thereof to be administered to the subject can be determined by persons skilled in the art depending on non-limiting factors such as the severity of the condition to be treated (e.g.. the size and number of nasal polyps), as well as the age and general health of the subject.
  • the therapeutically effective amount will typically fall within a relatively broad range that can be determined through routine trials by persons skilled in the art. Dosage regimes may be adjusted to provide the optimum therapeutic response, depending, for example, on the condition to be treated.
  • therapeutically effective combination refers to the combination of cromoglycic acid (or salt thereof) and the pharmaceutically-acceptable carrier, whereby they provide, in combination, the desired therapeutic effect (e.g., a reduction in the size of the nasal polyp when administered to the subject), as described elsewhere herein.
  • the pharmaceutically-acceptable carrier is understood to potentiate the therapeutic effect of the cromoglycic acid, or salt thereof, on the nasal polyp, such that the administration of the cromoglycic acid, or salt thereof, to the subject, when formulated in the absence of the pharmaceutically-acceptable carrier, will have no significant therapeutic effect on the nasal polyp (i.e., will not have a useful therapeutic effect).
  • the pharmaceutically-acceptable carrier potentiates the effect of the cromoglycic acid, or salt thereof, as determined, for example, by a reduction in the size of the nasal polyp in the subject.
  • the composition comprises from about 2.0% to about 10.0% cromoglycic acid, or a salt thereof, by weight of the total weight of the composition. In an embodiment, the composition comprises from about 4.25% to about 10% cromoglycic acid, or a salt thereof, by weight of the total weight of the composition. In an embodiment, the composition comprises from about 4.25% to about 8.0% cromoglycic acid, or a salt thereof, by weight of the total weight of the composition. In an embodiment, the composition comprises about 4% cromoglycic acid, or a salt thereof, by weight of the total weight of the composition. In an embodiment, the composition comprises from about 5.0% to about 8.0% cromoglycic acid, or a salt thereof, by weight of the total weight of the composition.
  • the composition comprises from about 5.0% to about 6.0% cromoglycic acid, or a salt thereof, by weight of the total weight of the composition. In an embodiment, the composition comprises about 6% cromoglycic acid, or a salt thereof, by weight of the total weight of the composition.
  • the subject has chronic rhinosinusitis with nasal polyps (CRSwNP), also referred to as nasal polyposis.
  • CRSwNP chronic rhinosinusitis with nasal polyps
  • chronic rhinosinusitis refers to inflammation of the sinonasal mucosa that persists for a period of greater than 12 weeks, characterized by one or more symptoms, non-limiting examples of which include nasal congestion, decreased or lost sense of smell, anterior and/or posterior nasal discharge, facial pain and/or headache.
  • Patients with CRS will often have one or more of the aforementioned symptoms for a period of years.
  • a formal diagnosis of CRS is typically made on the basis of sinus computed tomography (CT) scan and/or sinus endoscopy. Based on endoscopic evaluation, CRS can be clinically divided as CRSwNP or CRS without nasal polyps/nasal polyposis.
  • CT sinus computed tomography
  • the methods described herein are prescribed for the long-term treatment of subjects with chronic rhinosinusitis with bilateral nasal polyposis, who have persistent signs and symptoms despite treatment with intranasal corticosteroids (INCS).
  • the methods described herein are prescribed for the long-term treatment of subjects with bilateral nasal polyposis with associated chronic rhinosinusitis who have persistent signs and symptoms despite treatment with INCS, including subjects who also suffer from allergies to pollen, dust mite allergens and domestic pet allergens.
  • Nasal polyps are characterized by an overgrowth of tissue in one or more of the nasal cavities and typically present as teardrop-shaped growths that prolapse from the sinuses into the nose and/or sinuses, obstructing the sinuses and nasal passages.
  • the condition of having nasal polyps is also commonly referred to as nasal polyposis, characterized by the presence of multiple polyps in the upper nasal cavity, originating from the osteomeatal complex.
  • nasal polyposis is understood to be a T helper cell-2 (Th2)-driven inflammatory process affecting the mucosa of the nose and paranasal sinuses.
  • nasal polyposis is understood to be largely a T helper cell-1 (Thl)-driven inflammatory process in the Asian population.
  • Eosinophils and their products are thought to be a hallmark of nasal polyp-associated inflammation as elevated levels of interleukin-5 (IL- 5; promotes eosinophil survival and differentiation), eosinophil cationic protein (ECP), and eotaxin (eosinophil chemoattractant), factors that attract and activate eosinophils, are typically found in nasal polyps.
  • Eosinophils are the predominant inflammatory cell found in the sinuses and nasal polyps, and nasal polyps are also associated with elevated levels of circulating IgE in some patients.
  • bilateral nasal polyps means the presence of one or more nasal polyps at each side of the nasal cavity.
  • nasal polyposis associated with a variety of conditions that will be familial to persons skilled in the art illustrative examples of which include sinusitis (e.g., allergic or non-allergic sinusitis), rhinitis (e.g., allergic and non- all ergic rhinitis), rhinosinusitis (e.g. allergic or non-allergic rhinosinusitis), asthma (e.g., moderate-to-severe asthma), NS AID sensitivity (e.g., aspirin sensitivity), and infection, such as bacterial and fungal infection.
  • sinusitis e.g., allergic or non-allergic sinusitis
  • rhinitis e.g., allergic and non- all ergic rhinitis
  • rhinosinusitis e.g. allergic or non-allergic rhinosinusitis
  • asthma e.g., moderate-to-severe asthma
  • NS AID sensitivity e.g., aspirin sensitivity
  • a subject with nasal polyposis such as a patient with chronic rhinosinusitis with bilateral nasal polyposis, may have concomitant Samter's triad (defined by presence of nasal polyps, asthma, and aspirin and S AID sensitivity).
  • a subject with nasal polyposis may also have concomitant asthma, and/or other Th2 systemic conditions.
  • Bacterial infections include, for example, Staphylococcus aureus infections.
  • a subject with nasal polyposis may have a chronic pathogenic bacterial colonization or infection, e.g., Staphylococcus aureus.
  • the subject has recurring nasal polyposis, such as may be associated with recurring sinusitis.
  • the term "sinusitis” refers to any inflammatory condition characterized by inflammation of the paranasal sinuses, including inflammation of the maxillary, frontal, ethmoid and/or sphenoid paranasal sinuses.
  • the methods described herein are therefore suitable for the treatment of nasal polyposis associated with acute sinusitis, sub-acute sinusitis, chronic sinusitis and recurrent sinusitis.
  • Acute sinusitis is typically characterized by a sudden onset of cold-like symptoms such as runny, stuffy nose and facial pain that does not go away after 10 to 14 days.
  • Acute sinusitis typically lasts less than four weeks.
  • Sub-acute sinusitis lasts four to twelve weeks.
  • Chronic rhinosinusitis typically lasts twelve weeks or longer, and recurrent sinusitis is characterized by sinusitis episodes that occur three or more times in one year.
  • Patients with chronic rhinosinusitis will often present with chronic hyperplastic eosinophilic sinusitis, which is characterized by marked inflammation of the sinuses, increased eosinophils and mixed mononuclear cells, and a relative paucity of neutrophils.
  • Some of these patients will have one or more of associated nasal polyps, asthma, and aspirin or NSAID sensitivity in an embodiment, the method described herein is used to treat nasal polyposis in a subject who has chronic hyperplastic eosinophilic sinusitis.
  • allergic rhinosinusitis refers to rhinosinusitis that occurs when the subject's immune system responds to specific, non-infectious irritants, non-limiting examples of which include plant pollens, molds, dust mites, animal hair, industrial chemicals (including tobacco smoke), foods, medicines, and insect venom.
  • non-aJlergic rhinosinusitis refers to rhinosinusitis that is not due to an allergic reaction, such as from colds, allergies, and tissue irritants (e g., nasal sprays, cocaine, cigarette smoke and the like). Less commonly, sinuses can also become obstructed by tumors or growths.
  • allergic rhinitis refers to rhinitis that occurs when the subject's immune system responds to specific, non-infectious irritants, including abnormal immune responses through the production of IgE to extrinsic and intrinsic factors.
  • non-allergic rhinitis also known as vasomotor rhinitis
  • vasomotor rhinitis refers to rhinitis that is not due to an allergic reaction, that can be triggered by factors, non limiting example of which include cigarette smoke and other pollutants, strong odors, strong chemical environments, alcoholic beverages, cold, blockages in the nose, a deviated septum, infections and over-use of medications such as decongestants and/or nasal sprays (also known as rhinitis medicamentosa).
  • Symptoms of non-allergic rhinitis include constriction or inflammation in the nasal passages which leads to many of the same symptoms of allergic rhinitis.
  • rhinosinusitis typically refers to a condition that has symptoms of both rhinitis and sinusitis.
  • the term“rhinosinusitis” is preferred rather than “sinusitis” by many authors because it is believed that inflammation of the sinus lining is likely to also affect the nasal lining, which is continuous, hence rhinosinusitis.
  • rhinitis is considered different, where rhinitis (inflammation of the lining of the nose, including inferior turbinates) is often seen in allergies but sinus involvement (e.g., thickening of sinus mucosal lining, confirmed by sinus CT scans) may not occur.
  • non-allergic rhinosinusitis refers to rhinosinusitis caused by, for example, pregnancy, thyroid disorders as a side effect of certain blood pressure and/or topical OTC decongestant medications, structural abnormalities in the nasal septum, structural abnormalities in the nasal filtering structures (turbinates), and/or structural abnormalities in the sinus drainage tracts, nasal polyps and eosinophils.
  • This category also includes vasomotor rhinitis, hormone-induced rhinitis, chemical and irritant-induced rhinitis and rhinitis medicamentosa.
  • the method decreases the subject’s NPS by about 1 to about 8 points, preferably by 1 point, preferably by 2 points, preferably by 3 points, preferably by 4 points, preferably by 5 points, preferably by 6 points, preferably by 7 points, or more preferably by 8 points.
  • the method decreases the subject's NPS by about 1 point, or a fraction thereof; preferably by 2 points, or a fraction thereof; preferably by 3 points, or a fraction thereof; preferably by 4 points, or a fraction thereof; preferably by 5 points, or a fraction thereof; preferably by 6 poinfs, or a fraction thereof; preferably by 7 poinfs, or a fraction thereof; or more preferably by 8 points or a fraction thereof.
  • an NFS of 0 indicates the absence of nasal polyps; an NPS of 1 indicates the presence of small polyps that do not extend beyond the edge of the middle turbinate; an NPS of 2 indicates the presence of polyps that extend beyond the edge of the middle turbinate but do not extend beyond the superior margin of the inferior turbinate; an NPS of 3 indicates larger polyps that extend beyond the superior margin of the inferior turbinate but do not extend beyond the middle of the inferior turbinate; an NPS of 4 indicates larger polyps that extend beyond the middle of the inferior turbinate but do not touch the floor of the nose; and an NPS of 5 indicates large polyps that touch the floor of the nose.
  • the maximum score is 10 (i.e., 5 points per nasal cavity).
  • the method decreases the subject's NPS by about 1 to about 10 points, preferably by 1 point, preferably by 2 points, preferably by 3 points, preferably by 4 points, preferably by 5 points, preferably by 6 points, preferably by 7 points, preferably by 8, preferably by 9; or more preferably by 10 points.
  • the method decreases the subject's NPS by about 1 point, or a fraction thereof; preferably by 2 points, or a fraction thereof; preferably by 3 points, or a fraction thereof; preferably by 4 points, or a fraction thereof; preferably by 5 points, or a fraction thereof; preferably by 6 points, or a fraction thereof: preferably by 7 points, or a fraction thereof; preferably by 8 points or a fraction thereof: preferably by 9 points or a fraction thereof or more preferably by 10 points or a fraction thereof.
  • the change in NPS may also be represented as a proportion of the subject’s NPS prior to treatment.
  • the method decreases the subject's NPS by about 1%, preferably by about 2%, preferably by about 3%, preferably by about 4%, preferably by about 5%, preferably by about 6%, preferably by about 7%, preferably by about 8%, preferably by about 9%, preferably by about 10%, preferably by about 11%, preferably by about 12%, preferably by about 13%, preferably by about 14%, preferably by about 15%, preferably by about 16%, preferably by about 17%, preferably by about 18%, preferably by about 19%, preferably by about 20%, preferably by about 21%, preferably by about 22%, preferably by about 23%, preferably by about 24%, preferably by about 25%, preferably by about 26%, preferably by about 27%, preferably by about 28%, preferably by about 29%, preferably by about 30, preferably by about 31%, preferably by about
  • a decrease in congestion and/or obstruction can also be monitored.
  • the methods described herein can result, for example, in a decrease in congestion and or obstruction (i.e., achieving a lower number on the scale) from baseline compared to week 4 to w ? eek 16 after the commencement of treatment.
  • a decrease in congestion and/or obstruction from baseline e.g., from about 0.5, preferably about 1.0, preferably about 1.5, preferably about 2.0, preferably about 2.5 or more preferably about 3.0 or more
  • a decrease in post nasal drip can also be monitored.
  • the methods described herein can result, for example, in a decrease in post nasal drip (i.e., achieving a lower number on the scale) from baseline compared to week 4 to week 16 after the commencement of treatment.
  • a decrease in post nasal drip from baseline e.g., from about 0.5, preferably about 1.0, preferably about 1.5, preferably about 2.0, preferably about 2.5 or more preferably about 3.0 or more
  • the methods described herein result in a decrease in post nasal drip symptom score from baseline by about 0.5, preferably about 1.0, preferably about 1.5, preferably about 2.0, preferably about 2.5 or more preferably about 3.0 or more at week 4, week 8, week 12, or week 16 after the commencement of treatment.
  • the VAS is a measure to assess patient-related rhinosinusitis symptom severity on a scale of 1 to 10. Mild symptoms are indicated by a score of 0 to 3, moderate symptoms are indicated by a VAS score of >3 to 7, and severe symptoms are indicated by a VAS score of >7 to 10.
  • the methods described herein result in a decrease in VAS score from baseline of about 0.5 point, preferably about 1 point, preferably about 1.5 points, preferably about 2 points, preferably about 2.5 points, preferably about 3 points, preferably about 3.5 points, or more preferably about 4 points, or more at week 4, week 6 or week 12 after the commencement of treatment.
  • the decrease in VAS score can be detected as early as week 4, and as late as week 12 or later after the commencement of treatment in accordance with the methods described herein.
  • the methods described herein result in a decrease in ACQ5 score from baseline of at least 0.10 point at week 12 following initiation of treatment with the composition described herein.
  • the methods described herein result in a decrease in ACQ score from baseline of about 0.10 points, preferably about 0.15 points, preferably about 0.20 points, preferably about 0.25 points, preferably about 0.30 points, preferably about 0.35 points, preferably about 0.40 points, preferably about 0.45 points, preferably about 0.50 points, preferably about 0.55 points, preferably about 0.60 points, preferably about 0.65 points, preferably about 0.70 points, preferably about 0.75 points, preferably about 0.80 points, or more preferably about 0.85 points or more at week 4, week 6 or week 12 after the commencement of treatment.
  • the decrease in ACQ score may be detected as early as week 4, and as late as week 12 or later after the commencement of treatment in accordance with the methods described herein.
  • NPIF Nasal Peak Inspiratory Flow
  • NPIF Nasal Peak Inspiratory Flow
  • the efficacy of the methods described herein can also be determined by measuring the effect of physiological parameters, such as within the nasal cavities, e.g., by nasal endoscopy or computed tomography (CT) scan.
  • physiological parameters such as within the nasal cavities, e.g., by nasal endoscopy or computed tomography (CT) scan.
  • CT computed tomography
  • the methods described herein result in a decrease in Lund-Mackay score from baseline by about 0.10 points, preferably about 0.15 points, preferably about 0.20 points, preferably about 0.25 points, preferably about 0.30 points, preferably about 0.35 points, preferably about 0.40 points, preferably about 0.45 points, preferably about 0.50 points, preferably about 0.55 points, preferably about 0.60 points, preferably about 0.65 points, preferably about 0.70 points, preferably about 0.75 points, preferably about 0.80 points, or more preferably about 0.85 points or more at week 4, week 6 or week 12 after the commencement of treatment.
  • the decrease in Lund-Mackay score may be detected as early as week 4, and as late as week 12 or later after the commencement of treatment in accordance with the methods described herein.
  • the Lund- Kennedy and Modified Lund-Kennedy endoscopic scoring systems are described in Abhishek K R. (2018, Exp Rhino ! Otolaryngol. 2(4). ER0.000541) and Psaltis et al. (2014, Laryngoscope, 124( 10) : 2216-2223 ) .
  • the decrease in Modified Lund-Kennedy score may be detected as early as week 4, and as late as week 12 or later after the commencement of treatment in accordance with the methods described herein.
  • item scores are coded, summed, and transformed on a scale from 0 (worst possible health state measured by the questionnaire) to 100 (best possible health state).
  • Two standardized summary scores can also be calculated from the SF-36; the physical component summary (PCS) and the mental health component summary (MCS)
  • the nasal polyp related resource use questionnaire is a questionnaire of health care resource utilization for nasal polyposis, including specialist visits, emergency care visits, sick leaves, days off etc.
  • the poloxamer is selected from the group consisting of poloxamer 188, poloxamer 237 and poloxamer 407.
  • the poloxamer is poloxamer 407 (poly( ethylene glycol)-Z /oc&-poly(propylene glycol)-htock-poly( ethylene glycol).
  • the composition is formulated for administration as an aerosol, as a spray, as a nasal drop or as an ointment. In an embodiment, the composition is formulated for administration as an aerosol.
  • Example 2 Sodium cromoglycate reduces mast cell numbers in human nasal polyp tissue in an in vivo xenograft model
  • SCG formulations or prednisolone were epicutaneously applied to both ears daily (TO m ⁇ on each side of the same ear, a total of 14 applications). Mice were then killed at the end of the experiment and both ears and lymph nodes were collected for further analysis
  • a further control group was treated with a solution comprising 4% SCG formulated in saline only (i.e., without 10% Pluronic). This group showed no improvement over the study period, noting that the results were comparable to those seen in Group 1 (data not shown). Re suits

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Abstract

La présente invention concerne de manière générale des procédés et des compositions pour traiter des polypes nasaux, comprenant l'administration à un sujet qui en a besoin d'une composition comportant une combinaison thérapeutiquement efficace d'acide cromoglycique, ou d'un sel de celui-ci, et d'un support pharmaceutiquement acceptable.
PCT/AU2019/051254 2018-11-14 2019-11-14 Compositions et leurs utilisations WO2020097686A1 (fr)

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WO2003045331A2 (fr) * 2001-11-29 2003-06-05 Emisphere Technologies, Inc. Preparations pour une administration par voie orale d'acide cromoglycique
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WO2006105204A2 (fr) * 2005-03-28 2006-10-05 Isis Pharmaceuticals, Inc. Compositions et leurs utilisations associees au thymus et a la chimiokine regulee par activation (tarc)
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WO2015002703A1 (fr) * 2013-05-23 2015-01-08 Aztherapies, Inc Méthodes d'administration de cromolyne
WO2018044942A1 (fr) * 2016-08-31 2018-03-08 Patara Pharma, LLC Compositions de cromolyne pour le traitement de la toux chronique due à une fibrose pulmonaire idiopathique

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Publication number Priority date Publication date Assignee Title
US6225356B1 (en) * 2000-01-20 2001-05-01 Jones, Iii Tudor Cromolyn sodium containing composition and method of treatment for vilvar vestibulitis interstitial cystitis vukvar vaginitis and vaginitis dynea
US20030216329A1 (en) * 2001-04-24 2003-11-20 Robinson Cynthia B. Composition, formulations & kit for treatment of respiratory & lung disease with dehydroepiandrosterone(s) steroid & an anti-muscarinic agent(s)
US20040116785A1 (en) * 2001-05-14 2004-06-17 Bulat Paul I. System and method for delivering medical examination, treatment and assistance over a network
WO2003045331A2 (fr) * 2001-11-29 2003-06-05 Emisphere Technologies, Inc. Preparations pour une administration par voie orale d'acide cromoglycique
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