IL273485B2 - Preparations for improved administration of epinephrine and drug meters - Google Patents
Preparations for improved administration of epinephrine and drug metersInfo
- Publication number
- IL273485B2 IL273485B2 IL273485A IL27348520A IL273485B2 IL 273485 B2 IL273485 B2 IL 273485B2 IL 273485 A IL273485 A IL 273485A IL 27348520 A IL27348520 A IL 27348520A IL 273485 B2 IL273485 B2 IL 273485B2
- Authority
- IL
- Israel
- Prior art keywords
- pharmaceutical composition
- composition according
- polymeric matrix
- ester
- acceptable salt
- Prior art date
Links
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 title claims 19
- 229930182837 (R)-adrenaline Natural products 0.000 title claims 19
- 229960005139 epinephrine Drugs 0.000 title claims 19
- 229940079593 drug Drugs 0.000 title 1
- 239000003814 drug Substances 0.000 title 1
- 238000002360 preparation method Methods 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 48
- 239000011159 matrix material Substances 0.000 claims 26
- 150000002148 esters Chemical class 0.000 claims 17
- 150000003839 salts Chemical class 0.000 claims 17
- 108060003345 Adrenergic Receptor Proteins 0.000 claims 12
- 102000017910 Adrenergic receptor Human genes 0.000 claims 12
- 239000010408 film Substances 0.000 claims 11
- 229920000642 polymer Polymers 0.000 claims 8
- 229930015704 phenylpropanoid Natural products 0.000 claims 6
- 150000002995 phenylpropanoid derivatives Chemical class 0.000 claims 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims 5
- 241000196324 Embryophyta Species 0.000 claims 4
- 244000061408 Eugenia caryophyllata Species 0.000 claims 4
- 235000016639 Syzygium aromaticum Nutrition 0.000 claims 4
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 claims 4
- 150000004676 glycans Chemical class 0.000 claims 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 4
- 239000003961 penetration enhancing agent Substances 0.000 claims 4
- 229920001282 polysaccharide Polymers 0.000 claims 4
- 239000005017 polysaccharide Substances 0.000 claims 4
- 239000000341 volatile oil Substances 0.000 claims 4
- 229920001577 copolymer Polymers 0.000 claims 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 3
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims 2
- SCCDQYPEOIRVGX-UHFFFAOYSA-N Acetyleugenol Chemical compound COC1=CC(CC=C)=CC=C1OC(C)=O SCCDQYPEOIRVGX-UHFFFAOYSA-N 0.000 claims 2
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 claims 2
- 239000005770 Eugenol Substances 0.000 claims 2
- 108010010803 Gelatin Proteins 0.000 claims 2
- 208000010496 Heart Arrest Diseases 0.000 claims 2
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 claims 2
- 235000010489 acacia gum Nutrition 0.000 claims 2
- RGIBXDHONMXTLI-UHFFFAOYSA-N chavicol Chemical compound OC1=CC=C(CC=C)C=C1 RGIBXDHONMXTLI-UHFFFAOYSA-N 0.000 claims 2
- 229930016911 cinnamic acid Natural products 0.000 claims 2
- 235000013985 cinnamic acid Nutrition 0.000 claims 2
- 229960002217 eugenol Drugs 0.000 claims 2
- 229920000159 gelatin Polymers 0.000 claims 2
- 239000008273 gelatin Substances 0.000 claims 2
- 235000019322 gelatine Nutrition 0.000 claims 2
- 235000011852 gelatine desserts Nutrition 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 239000000651 prodrug Substances 0.000 claims 2
- 229940002612 prodrug Drugs 0.000 claims 2
- ZMQAAUBTXCXRIC-UHFFFAOYSA-N safrole Chemical compound C=CCC1=CC=C2OCOC2=C1 ZMQAAUBTXCXRIC-UHFFFAOYSA-N 0.000 claims 2
- 150000003505 terpenes Chemical class 0.000 claims 2
- 208000003663 ventricular fibrillation Diseases 0.000 claims 2
- CRDAMVZIKSXKFV-FBXUGWQNSA-N (2-cis,6-cis)-farnesol Chemical compound CC(C)=CCC\C(C)=C/CC\C(C)=C/CO CRDAMVZIKSXKFV-FBXUGWQNSA-N 0.000 claims 1
- 239000000260 (2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-ol Substances 0.000 claims 1
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 claims 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims 1
- 102000009027 Albumins Human genes 0.000 claims 1
- 108010088751 Albumins Proteins 0.000 claims 1
- 206010002198 Anaphylactic reaction Diseases 0.000 claims 1
- 208000037874 Asthma exacerbation Diseases 0.000 claims 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims 1
- IAZKGRRJAULWNS-UHFFFAOYSA-N Chavicol Natural products OC1=CC=C(CCC=C)C=C1 IAZKGRRJAULWNS-UHFFFAOYSA-N 0.000 claims 1
- 229920002101 Chitin Polymers 0.000 claims 1
- 229920001661 Chitosan Polymers 0.000 claims 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 claims 1
- 102000008186 Collagen Human genes 0.000 claims 1
- 108010035532 Collagen Proteins 0.000 claims 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- 229920002907 Guar gum Polymers 0.000 claims 1
- 229920000084 Gum arabic Polymers 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims 1
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 claims 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims 1
- 208000001953 Hypotension Diseases 0.000 claims 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 claims 1
- 208000006550 Mydriasis Diseases 0.000 claims 1
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- 239000004372 Polyvinyl alcohol Substances 0.000 claims 1
- 239000004373 Pullulan Substances 0.000 claims 1
- 229920001218 Pullulan Polymers 0.000 claims 1
- 206010058151 Pulseless electrical activity Diseases 0.000 claims 1
- 229920002125 Sokalan® Polymers 0.000 claims 1
- 229920002472 Starch Polymers 0.000 claims 1
- AXMVYSVVTMKQSL-UHFFFAOYSA-N UNPD142122 Natural products OC1=CC=C(C=CC=O)C=C1O AXMVYSVVTMKQSL-UHFFFAOYSA-N 0.000 claims 1
- 206010047281 Ventricular arrhythmia Diseases 0.000 claims 1
- 239000000205 acacia gum Substances 0.000 claims 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 230000036783 anaphylactic response Effects 0.000 claims 1
- 208000003455 anaphylaxis Diseases 0.000 claims 1
- 230000006793 arrhythmia Effects 0.000 claims 1
- 230000001851 biosynthetic effect Effects 0.000 claims 1
- 230000017531 blood circulation Effects 0.000 claims 1
- 230000036471 bradycardia Effects 0.000 claims 1
- 239000001768 carboxy methyl cellulose Substances 0.000 claims 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims 1
- -1 cinnamic acid ester Chemical class 0.000 claims 1
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 claims 1
- 229940117916 cinnamic aldehyde Drugs 0.000 claims 1
- 229920001436 collagen Polymers 0.000 claims 1
- 239000006071 cream Substances 0.000 claims 1
- 239000000412 dendrimer Substances 0.000 claims 1
- 229920000736 dendritic polymer Polymers 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 229930002886 farnesol Natural products 0.000 claims 1
- 229940043259 farnesol Drugs 0.000 claims 1
- 238000011010 flushing procedure Methods 0.000 claims 1
- 239000000499 gel Substances 0.000 claims 1
- 239000000665 guar gum Substances 0.000 claims 1
- 235000010417 guar gum Nutrition 0.000 claims 1
- 229960002154 guar gum Drugs 0.000 claims 1
- 229920000591 gum Polymers 0.000 claims 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims 1
- 229920000587 hyperbranched polymer Polymers 0.000 claims 1
- 230000036543 hypotension Effects 0.000 claims 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 claims 1
- 235000020778 linoleic acid Nutrition 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- JZRYQZJSTWVBBD-UHFFFAOYSA-N pentaporphyrin i Chemical class N1C(C=C2NC(=CC3=NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 JZRYQZJSTWVBBD-UHFFFAOYSA-N 0.000 claims 1
- 229920002627 poly(phosphazenes) Polymers 0.000 claims 1
- 239000004584 polyacrylic acid Substances 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 229920002451 polyvinyl alcohol Polymers 0.000 claims 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims 1
- 235000019423 pullulan Nutrition 0.000 claims 1
- 229930004725 sesquiterpene Natural products 0.000 claims 1
- 150000004354 sesquiterpene derivatives Chemical class 0.000 claims 1
- 235000010413 sodium alginate Nutrition 0.000 claims 1
- 239000000661 sodium alginate Substances 0.000 claims 1
- 229940005550 sodium alginate Drugs 0.000 claims 1
- 239000007921 spray Substances 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 claims 1
- 235000019698 starch Nutrition 0.000 claims 1
- 239000008107 starch Substances 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- 235000007586 terpenes Nutrition 0.000 claims 1
- CRDAMVZIKSXKFV-UHFFFAOYSA-N trans-Farnesol Natural products CC(C)=CCCC(C)=CCCC(C)=CCO CRDAMVZIKSXKFV-UHFFFAOYSA-N 0.000 claims 1
- 229940124549 vasodilator Drugs 0.000 claims 1
- 239000003071 vasodilator agent Substances 0.000 claims 1
- 208000021816 ventricular bradycardia Diseases 0.000 claims 1
- 229920003169 water-soluble polymer Polymers 0.000 claims 1
- 229920001285 xanthan gum Polymers 0.000 claims 1
- 239000000230 xanthan gum Substances 0.000 claims 1
- 235000010493 xanthan gum Nutrition 0.000 claims 1
- 229940082509 xanthan gum Drugs 0.000 claims 1
Classifications
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/49—Cinchonan derivatives, e.g. quinine
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- 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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Emergency Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Botany (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
Claims (50)
1. A pharmaceutical composition, comprising: a polymeric matrix in a pharmaceutical film; pharmaceutically active component including epinephrine or pharmaceutically acceptable salt or ester thereof contained in the polymeric matrix; and an adrenergic receptor interacter that modifies or otherwise alters the action of an adrenergic receptor, the pharmaceutical film having a Tmax of 5-60 minutes, and a Cmax of 0.1 ng/ml-ng/ml.
2. The pharmaceutical composition according to claim 1, further comprising a permeation enhancer in addition to the adrenergic receptor interacter.
3. The pharmaceutical composition according to claim 1, wherein the composition is a film further comprising a polymeric matrix, the pharmaceutically active component being contained in the polymeric matrix.
4. The pharmaceutical composition according to claim 2, wherein the permeation enhancer includes a phenylpropanoid.
5. The pharmaceutical composition according to claim 2, wherein the permeation enhancer includes farnesol or Labrasol.
6. The pharmaceutical composition according to claim 2, wherein the permeation enhancer includes linoleic acid.
7. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a film further comprising a polymeric matrix, the pharmaceutically active component being contained in the polymeric matrix. 273485/
8. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a chewable or gelatin based dosage form, spray, gum, gel, cream, tablet, liquid or film.
9. The pharmaceutical composition according to claim 4, wherein the phenylpropanoid is eugenol or eugenol acetate.
10. The pharmaceutical composition according to claim 4, wherein the phenylpropanoid is a cinnamic acid, cinnamic acid ester, cinnamic aldehyde or hydrocinnamic acid.
11. The pharmaceutical composition according to claim 4, wherein the phenylpropanoid is chavicol.
12. The pharmaceutical composition according to claim 4, wherein the phenylpropanoid is safrole.
13. The pharmaceutical composition according to claim 1, wherein the adrenergic receptor interacter is a phytoextract.
14. The pharmaceutical composition according to claim 13, wherein the phytoextract further includes an essential oil extract of a clove plant.
15. The pharmaceutical composition according to claim 13, wherein the phytoextract further includes an essential oil extract of a leaf of a clove plant.
16. The pharmaceutical composition according to claim 13, wherein the phytoextract further includes an essential oil extract of a flower bud of a clove plant.
17. The pharmaceutical composition according to claim 13, wherein the phytoextract further includes an essential oil extract of a stem of a clove plant. 273485/
18. The pharmaceutical composition according to claim 13, wherein the phytoextract is synthetic or biosynthetic.
19. The pharmaceutical composition according to claim 13, wherein the phytoextract further includes 40-95% eugenol.
20. The pharmaceutical composition according to claim 1, wherein the adrenergic receptor interacter includes a terpenoid, terpene or a sesquiterpene.
21. The pharmaceutical composition according to claim 1, wherein the polymer matrix includes a polymer.
22. The pharmaceutical composition according to claim 21, wherein the polymer is a water soluble polymer.
23. The pharmaceutical composition according to claim 21, wherein the polymer includes a polyethylene oxide.
24. The pharmaceutical composition according to claim 21, wherein the polymer includes a cellulosic polymer is selected from the group of: hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, methylcellulose and carboxymethyl cellulose.
25. The pharmaceutical composition according to claim 21, wherein the polymeric matrix comprises a cellulosic polymer, polyethylene oxide and polyvinyl pyrrolidone, polyethylene oxide and a polysaccharide, polyethylene oxide, hydroxypropyl methylcellulose and a polysaccharide, or polyethylene oxide, hydroxypropyl methylcellulose, polysaccharide and polyvinylpyrrolidone.
26. The pharmaceutical composition according to claim 21, wherein the polymeric matrix comprises at least one polymer selected from the group of: pullulan, polyvinyl pyrrolidone, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, ethylene oxide- 273485/ propylene oxide co-polymers, collagen, albumin, poly-amino acids, polyphosphazenes, polysaccharides, chitin, chitosan, and derivatives thereof
27. The pharmaceutical composition according to claim 1, further comprising a stabilizer.
28. The pharmaceutical composition according to claim 1, wherein the polymeric matrix comprises a dendritic polymer or a hyperbranched polymer.
29. A method of making a pharmaceutical composition comprising: combining an adrenergic receptor interacter that modifies or otherwise alters the action of an adrenergic receptor, with a pharmaceutically active component including epinephrine or a pharmaceutically acceptable salt or ester thereof and forming a pharmaceutical composition including the adrenergic receptor interacter and the pharmaceutically active component.
30. A device comprising a housing that holds an amount of a pharmaceutical composition, comprising: a polymeric matrix; a pharmaceutically active component including epinephrine or a pharmaceutically acceptable salt or ester thereof in the polymeric matrix; and a phenylpropanoid and/or a phytoextract; and an opening that dispenses a predetermined amount of the pharmaceutical composition.
31. A pharmaceutical composition, comprising: a polymeric matrix; 273485/ a pharmaceutically active component including epinephrine or a pharmaceutically acceptable salt or ester thereof in the polymeric matrix; and a porphine alkaloid interacter.
32. A pharmaceutical composition, comprising: a polymeric matrix; a pharmaceutically active component including epinephrine or a pharmaceutically acceptable salt or ester thereof in the polymeric matrix; and a vasodilator interacter.
33. A pharmaceutical composition, comprising: a polymeric matrix; a pharmaceutically active component including epinephrine or a pharmaceutically acceptable salt or ester thereof in the polymeric matrix; and an interacter that creates increased blood flow or enables a flushing of the tissue to modify transmucosal uptake of the pharmaceutically active component.
34. A pharmaceutical composition, comprising: a polymeric matrix; a pharmaceutically active component including epinephrine or its prodrug in the polymeric matrix; and an interacter that has a positive or negative heat of solution which are used as aids to modify transmucosal uptake.
35. A pharmaceutical composition, comprising: a polymeric matrix; 273485/ a pharmaceutically active component including epinephrine or a pharmaceutically acceptable salt or ester thereof in the polymeric matrix; and an interacter as defined in any one of claims 31 to 34, the composition contained in a multilayer film having at least one side where the edges are coterminous.
36. A an effective amount of a pharmaceutical composition comprising: a polymeric matrix; pharmaceutically active component including epinephrine pharmaceutically acceptable salt or ester thereof in the polymeric matrix; and an adrenergic receptor interacter that modifies or otherwise alters the action of an adrenergic receptor, for use in a method of treating a medical condition.
37. The pharmaceutical composition for use of claim 35, wherein the prodrug is dipifevrin.
38. The pharmaceutical composition for use of claim 35, wherein the medical condition includes hypotension, cardiac arrest, heart failure, anaphylaxis, mydriasis, asystole, pulseless electrical activity, ventricular fibrillation, pulseless ventricular tachycardia, bradycardia, arrhythmia, or asthma exacerbation.
39. The pharmaceutical composition according to claim 1, wherein the epinephrine or a pharmaceutically acceptable salt or ester thereof is dipifevrin.
40. The method of claim 29, wherein the epinephrine or a pharmaceutically acceptable salt or ester thereof is dipifevrin.
41. The device of claim 30, wherein the epinephrine or a pharmaceutically acceptable salt or ester thereof is dipifevrin.
42. The pharmaceutical composition according to claim 31, wherein the epinephrine or a pharmaceutically acceptable salt or ester thereof is dipifevrin. 273485/
43. The pharmaceutical composition according to claim 32, wherein the epinephrine or pharmaceutically acceptable salt or ester thereof is dipifevrin.
44. The pharmaceutical composition according to claim 33, wherein the epinephrine or a pharmaceutically acceptable salt or ester thereof is dipifevrin.
45. The pharmaceutical composition according to claim 34, wherein the epinephrine or a pharmaceutically acceptable salt or ester thereof is dipifevrin.
46. The pharmaceutical composition according to claim 35, wherein the epinephrine or a pharmaceutically acceptable salt or ester thereof is dipifevrin.
47. A pharmaceutical film, comprising: a polymeric matrix; pharmaceutically active component including epinephrine or a pharmaceutically acceptable salt or ester thereof contained in the polymeric matrix and an adrenergic receptor, interacter that modifies or otherwise alters the action of an adrenergic receptor; the pharmaceutical film having a Tmax of 5-60 minutes, and a Cmax of 0.ng/ml-2 ng/ml.
48. The pharmaceutical film of claim 47, wherein the Tmax is 40 minutes or less and wherein the Cmax is 0.1 ng/ml or greater.
49. The pharmaceutical film of claim 47, wherein the Tmax is 35 minutes or less and wherein the Cmax is 0.15 ng/ml or greater.
50. The pharmaceutical film of claim 47, wherein the Tmax is 30 minutes or less and wherein the Cmax is 0.2 ng/ml or greater. 273485/
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|---|---|---|---|
| US15/717,859 US20180125977A1 (en) | 2016-05-05 | 2017-09-27 | Enhanced delivery epinephrine compositions |
| US15/791,249 US20180104195A1 (en) | 2016-05-05 | 2017-10-23 | Enhanced delivery epinephrine compositions |
| PCT/US2018/053042 WO2019067670A1 (en) | 2017-09-27 | 2018-09-27 | Enhanced delivery epinephrine and prodrug compositions |
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| IL273485A IL273485A (en) | 2020-05-31 |
| IL273485B1 IL273485B1 (en) | 2024-07-01 |
| IL273485B2 true IL273485B2 (en) | 2024-11-01 |
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| JP2019519487A (en) | 2016-05-05 | 2019-07-11 | アクエスティブ セラピューティクス インコーポレイテッド | Delivery enhancing epinephrine composition |
| US11273131B2 (en) | 2016-05-05 | 2022-03-15 | Aquestive Therapeutics, Inc. | Pharmaceutical compositions with enhanced permeation |
| AU2020373100A1 (en) | 2019-11-01 | 2022-05-19 | Aquestive Therapeutics, Inc. | Prodrug compositions and methods of treatment |
| US11571468B2 (en) * | 2021-02-01 | 2023-02-07 | Matthias W. Rath | Micronutrient combination to reduce blood pressure |
| WO2023245069A2 (en) * | 2022-06-14 | 2023-12-21 | Aquestive Therapeutics, Inc. | Enhanced delivery epinephrine and prodrug compositions |
| EP4302751A1 (en) * | 2022-07-07 | 2024-01-10 | LTS Lohmann Therapie-Systeme AG | Oral thin films with low water activity |
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| WO2017192923A1 (en) * | 2016-05-05 | 2017-11-09 | Monosol Rx, Llc | Pharmaceutical compositions with enhanced permeation |
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| US8603514B2 (en) | 2002-04-11 | 2013-12-10 | Monosol Rx, Llc | Uniform films for rapid dissolve dosage form incorporating taste-masking compositions |
| US7666337B2 (en) | 2002-04-11 | 2010-02-23 | Monosol Rx, Llc | Polyethylene oxide-based films and drug delivery systems made therefrom |
| US7357891B2 (en) | 2001-10-12 | 2008-04-15 | Monosol Rx, Llc | Process for making an ingestible film |
| US7425292B2 (en) | 2001-10-12 | 2008-09-16 | Monosol Rx, Llc | Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom |
| US8765167B2 (en) | 2001-10-12 | 2014-07-01 | Monosol Rx, Llc | Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions |
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| US20040096569A1 (en) * | 2002-11-15 | 2004-05-20 | Barkalow David G. | Edible film products and methods of making same |
| US20050266085A1 (en) * | 2004-05-28 | 2005-12-01 | Warner Kevin S | Gelled emulsion and microemulsion formulations for dermal drug delivery |
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2018
- 2018-09-27 IL IL273485A patent/IL273485B2/en unknown
- 2018-09-27 EP EP18786593.6A patent/EP3687510A1/en active Pending
- 2018-09-27 IL IL313551A patent/IL313551A/en unknown
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| US20070202163A1 (en) * | 2005-09-09 | 2007-08-30 | Mutasem Rawas-Qalaji | Fast-disintegrating epinephrine tablets for buccal or sublingual administration |
| WO2017192921A1 (en) * | 2016-05-05 | 2017-11-09 | Monosol Rx, Llc | Enhanced delivery epinephrine compositions |
| WO2017192923A1 (en) * | 2016-05-05 | 2017-11-09 | Monosol Rx, Llc | Pharmaceutical compositions with enhanced permeation |
Also Published As
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|---|---|
| WO2019067670A1 (en) | 2019-04-04 |
| CN111465391A (en) | 2020-07-28 |
| JP2020535162A (en) | 2020-12-03 |
| IL273485A (en) | 2020-05-31 |
| JP2023159150A (en) | 2023-10-31 |
| IL273485B1 (en) | 2024-07-01 |
| KR20200060748A (en) | 2020-06-01 |
| CA3076816A1 (en) | 2019-04-04 |
| EP3687510A1 (en) | 2020-08-05 |
| IL313551A (en) | 2024-08-01 |
| BR112020005948A2 (en) | 2020-12-01 |
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