CA2135203C - Metering spray designed for pernasal application - Google Patents
Metering spray designed for pernasal applicationInfo
- Publication number
- CA2135203C CA2135203C CA002135203A CA2135203A CA2135203C CA 2135203 C CA2135203 C CA 2135203C CA 002135203 A CA002135203 A CA 002135203A CA 2135203 A CA2135203 A CA 2135203A CA 2135203 C CA2135203 C CA 2135203C
- Authority
- CA
- Canada
- Prior art keywords
- sex hormone
- spray
- application
- testosterone
- dopamine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000007921 spray Substances 0.000 title claims abstract description 16
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims abstract description 22
- 239000003163 gonadal steroid hormone Substances 0.000 claims abstract description 13
- 229960003604 testosterone Drugs 0.000 claims abstract description 10
- 239000002243 precursor Substances 0.000 claims abstract description 8
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 12
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 claims description 11
- 239000013543 active substance Substances 0.000 claims description 7
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 claims description 7
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 claims description 4
- 230000008499 blood brain barrier function Effects 0.000 claims description 4
- 210000001218 blood-brain barrier Anatomy 0.000 claims description 4
- 229960003638 dopamine Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 3
- 230000004060 metabolic process Effects 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 abstract description 4
- 230000000035 biogenic effect Effects 0.000 abstract description 4
- 150000003943 catecholamines Chemical class 0.000 abstract description 3
- 230000002503 metabolic effect Effects 0.000 abstract description 2
- 208000018737 Parkinson disease Diseases 0.000 description 4
- 230000036765 blood level Effects 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000009471 action Effects 0.000 description 3
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000007922 nasal spray Substances 0.000 description 2
- 229940097496 nasal spray Drugs 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000003304 psychophysiological effect Effects 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 108010085012 Steroid Receptors Proteins 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 210000003695 paranasal sinus Anatomy 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- -1 polyoxyethylene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 102000005969 steroid hormone receptors Human genes 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Otolaryngology (AREA)
- Emergency Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Described is a metering spray designed for pernasal application, the spray containing at least one sex hormone or at least one metabolic precursor of a sex hormone or at least one derivative of a sex hormone or combinations of these, excepting the precursors of testosterone, or at least one biogenic amine, with the exception of catecholamines.
Description
f~ gj 3 -METERING SPRAY DESIGNED FOR PERNASAL APPLICATION
The invention relates to the use of novel dosing or metering sprays for pernasal application.
Numerous pharmaceutical substances have their pharmacodynamic action in the central nervous system. Thus, the latest research has revealed that sex hormones and their derivatives in part reveal unexpected, positive side-effects in the central nervous system, particularly in that the general psychophysiological stressability of the patient perceptibly rises. Other substances, such as certain biogenic amines have a therapeutic activity which is directly dependent on a facilitated access to the central nervous system. This is a decisive action prerequisite for example, for medicaments for treating Parkinson's disease, such as, for example, dopamine, dopamine derivatives, NADH or NADPH.
If, as a result of their chemical properties, active substances undergo modifications in the gastrointestinal tract due to the varying pH-conditions and enzymatic processes (such as e.g. most biogenic amines) or if they are only water-soluble to a limited extent (such as sex hormones) hitherto complicated galenic administration forms have been necessary, or it has been necessary to use the parenteral administration form, which stresses the patient and requires the calling in of the doctor.
EP-A-272 097 points out that progesterone from the nasal cavity is absorbed in such a way that the resulting blood levels are virtually equivalent to intravenous administration.
EP-A-160 501 discloses an intranasal formulation for catecholamine, which is suspended fatty acid or ester and emulsified with polyoxyethylene.
The object of the present invention is to provide an administration form, which favours the access of certain r_ active substances to the central nervous system and therefore permits a reduction in the single dose and/or supply of active substances, which cannot be perorally supplied for the indicated reasons.
According to the invention this object is achieved by a dosing spray having a content of at least one sex hormone or at least one metabolic precursor of a sex hormone or a combination thereof, excepting the precursors of testosterone, or at least one biogenic amine, excepting catecholamines.
Particular preference is given to a dosing spray having a content of dopamine, dopamine derivative, NADH, NADPH or a combination thereof.
Thus, according to the invention, there is provided a use of at least one sex hormone or at least one precursor of a sex hormone in the metabolic process or at least one derivative of a sex hormone or of a combination thereof, apart from the precursors of testosterone or of dopamine, a dopamine derivative, NADH, NADPH or a combination thereof for producing a medicament in the form of a dispensing spray for pernasal application for controlled dosage reduction or for facilitating the passage through the blood-brain barrier.
The preferred dosage is from 2 to 20 mg of active substance per spray stroke.
Further features and advantages of the invention can be gathered from the following description of a preferred embodiment.
Ap~lication of testosterone by means of a dosinq sPraY
The advantages of administration by means of a dosing spray were tested in comparison with the oral administration of testosterone.
~.-~7.' ~
_ ' The peroral supply of 100 mg of testosterone by means of a capsule increased the blood level from a starting concentration between 32.5 and 37.5 nmole/l to values between 45 and 50 nmole/l. The concentration maximum was reached 30 minutes after administration, but was subject to marked individual fluctuations.
The profile of the steroids eliminated in the urine reacted very strongly and there were increases in the testosterone/epitestosterone quotient starting from the normal range between 0.9 and 2.8 to values of up to 60.
The blood level kinetics individually varied widely and in part 60 to 90 minutes following administration the initial values were again reached.
When testosterone was administered by means of a nasal spray, only a dose of 7 or 14 mg per application was needed in order to achieve the same rise in the blood level.
Application was much better to control. The blood concentrations which increased in individual test persons in a stable manner were 1.5 to 2 times the individual starting concentrations. The time during which the maximum blood concentration was reached was clearly reduced to from 15 to a maximum of 90 minutes.
The disturbances in the urine steroid profile were clearly reduced and the testosterone/epitestosterone quotient only rose to values between 15 and 20 and was normalized within 24 3 0 hours .
Following pernasal application all the test persons mentionedan improved psychophysiological stressability. This effect was not observed with peroral administration. It is attributed to the preferred influencing of the central nervous steroid receptors, probably caused by easier passage through the blood-brain barrier in pernasal application.
FJ
A~plication of anti-Parkinson's disease aqents For therapeutics used in the treatment of Parkinson's disease, an essential action prerequisite is the passage through the blood-brain barrier.
Building up on the aforementioned results NADH was pernasally applied in a pilot study. In pilot studies with parenteral administration of 5 to 10 mg of NADH (infusion over 30 minutes it was found that the tremor frequency significantly decreased and both the mobility and target accuracy or aim of the movements improved. For the same dosage intranasal NADH
application revealed the same action. Thus, it is possible to avoid the risky, stressing intravenous infusion and instead to obtain by means of the dosing spray an application which is more appropriate for the disease and age.
In the case of pernasal application the active substance can also be available in powder form. As a result of the spray stroke there is a very fine distribution in the vicinity of the nose and nasal sinuses, which favours absorption over a large surface. The galenic formulation as a dry substance eliminates the problems associated with the keeping quality and stability of the active substance. The preferred administration as a nasal spray is consequently particularly suitable for out-patient therapy of Parkinson's disease.
The features of the invention disclosed in the description and claims can be essential to the implementation of the invention in its various embodiments either singly or in random combination.
The invention relates to the use of novel dosing or metering sprays for pernasal application.
Numerous pharmaceutical substances have their pharmacodynamic action in the central nervous system. Thus, the latest research has revealed that sex hormones and their derivatives in part reveal unexpected, positive side-effects in the central nervous system, particularly in that the general psychophysiological stressability of the patient perceptibly rises. Other substances, such as certain biogenic amines have a therapeutic activity which is directly dependent on a facilitated access to the central nervous system. This is a decisive action prerequisite for example, for medicaments for treating Parkinson's disease, such as, for example, dopamine, dopamine derivatives, NADH or NADPH.
If, as a result of their chemical properties, active substances undergo modifications in the gastrointestinal tract due to the varying pH-conditions and enzymatic processes (such as e.g. most biogenic amines) or if they are only water-soluble to a limited extent (such as sex hormones) hitherto complicated galenic administration forms have been necessary, or it has been necessary to use the parenteral administration form, which stresses the patient and requires the calling in of the doctor.
EP-A-272 097 points out that progesterone from the nasal cavity is absorbed in such a way that the resulting blood levels are virtually equivalent to intravenous administration.
EP-A-160 501 discloses an intranasal formulation for catecholamine, which is suspended fatty acid or ester and emulsified with polyoxyethylene.
The object of the present invention is to provide an administration form, which favours the access of certain r_ active substances to the central nervous system and therefore permits a reduction in the single dose and/or supply of active substances, which cannot be perorally supplied for the indicated reasons.
According to the invention this object is achieved by a dosing spray having a content of at least one sex hormone or at least one metabolic precursor of a sex hormone or a combination thereof, excepting the precursors of testosterone, or at least one biogenic amine, excepting catecholamines.
Particular preference is given to a dosing spray having a content of dopamine, dopamine derivative, NADH, NADPH or a combination thereof.
Thus, according to the invention, there is provided a use of at least one sex hormone or at least one precursor of a sex hormone in the metabolic process or at least one derivative of a sex hormone or of a combination thereof, apart from the precursors of testosterone or of dopamine, a dopamine derivative, NADH, NADPH or a combination thereof for producing a medicament in the form of a dispensing spray for pernasal application for controlled dosage reduction or for facilitating the passage through the blood-brain barrier.
The preferred dosage is from 2 to 20 mg of active substance per spray stroke.
Further features and advantages of the invention can be gathered from the following description of a preferred embodiment.
Ap~lication of testosterone by means of a dosinq sPraY
The advantages of administration by means of a dosing spray were tested in comparison with the oral administration of testosterone.
~.-~7.' ~
_ ' The peroral supply of 100 mg of testosterone by means of a capsule increased the blood level from a starting concentration between 32.5 and 37.5 nmole/l to values between 45 and 50 nmole/l. The concentration maximum was reached 30 minutes after administration, but was subject to marked individual fluctuations.
The profile of the steroids eliminated in the urine reacted very strongly and there were increases in the testosterone/epitestosterone quotient starting from the normal range between 0.9 and 2.8 to values of up to 60.
The blood level kinetics individually varied widely and in part 60 to 90 minutes following administration the initial values were again reached.
When testosterone was administered by means of a nasal spray, only a dose of 7 or 14 mg per application was needed in order to achieve the same rise in the blood level.
Application was much better to control. The blood concentrations which increased in individual test persons in a stable manner were 1.5 to 2 times the individual starting concentrations. The time during which the maximum blood concentration was reached was clearly reduced to from 15 to a maximum of 90 minutes.
The disturbances in the urine steroid profile were clearly reduced and the testosterone/epitestosterone quotient only rose to values between 15 and 20 and was normalized within 24 3 0 hours .
Following pernasal application all the test persons mentionedan improved psychophysiological stressability. This effect was not observed with peroral administration. It is attributed to the preferred influencing of the central nervous steroid receptors, probably caused by easier passage through the blood-brain barrier in pernasal application.
FJ
A~plication of anti-Parkinson's disease aqents For therapeutics used in the treatment of Parkinson's disease, an essential action prerequisite is the passage through the blood-brain barrier.
Building up on the aforementioned results NADH was pernasally applied in a pilot study. In pilot studies with parenteral administration of 5 to 10 mg of NADH (infusion over 30 minutes it was found that the tremor frequency significantly decreased and both the mobility and target accuracy or aim of the movements improved. For the same dosage intranasal NADH
application revealed the same action. Thus, it is possible to avoid the risky, stressing intravenous infusion and instead to obtain by means of the dosing spray an application which is more appropriate for the disease and age.
In the case of pernasal application the active substance can also be available in powder form. As a result of the spray stroke there is a very fine distribution in the vicinity of the nose and nasal sinuses, which favours absorption over a large surface. The galenic formulation as a dry substance eliminates the problems associated with the keeping quality and stability of the active substance. The preferred administration as a nasal spray is consequently particularly suitable for out-patient therapy of Parkinson's disease.
The features of the invention disclosed in the description and claims can be essential to the implementation of the invention in its various embodiments either singly or in random combination.
Claims (2)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. Use of at least one sex hormone or at least one precursor of a sex hormone in a metabolic process or at least one derivative of a sex hormone or of a combination thereof, apart from the precursors of testosterone or of dopamine, a dopamine derivative, NADH, NADPH or a combination thereof for producing a medicament in the form of a dispensing spray for pernasal application for controlled dosage reduction or for facilitating the passage through the blood-brain barrier.
2. Use according to claim 1, wherein the dispensing spray is applied at a dosage of from 2 to 20 mg active substance per spray stroke.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP4218291.3 | 1992-06-03 | ||
| DE19924218291 DE4218291A1 (en) | 1992-06-03 | 1992-06-03 | Dosing spray for pernasal application |
| PCT/DE1993/000442 WO1993024107A1 (en) | 1992-06-03 | 1993-05-17 | Metering spray designed for pernasal application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2135203A1 CA2135203A1 (en) | 1993-12-09 |
| CA2135203C true CA2135203C (en) | 1998-12-29 |
Family
ID=6460299
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002135203A Expired - Lifetime CA2135203C (en) | 1992-06-03 | 1993-05-17 | Metering spray designed for pernasal application |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0643575B1 (en) |
| JP (1) | JP3705600B2 (en) |
| CA (1) | CA2135203C (en) |
| DE (2) | DE4218291A1 (en) |
| ES (1) | ES2085775T3 (en) |
| WO (1) | WO1993024107A1 (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2735293A1 (en) * | 1995-01-17 | 1996-07-18 | Menuco Corp. | Nadh and nadph therapeutic agents for dermal administration |
| US5712259A (en) * | 1996-04-22 | 1998-01-27 | Birkmayer Pharmaceuticals | NADH and NADPH pharmaceuticals for treating chronic fatigue syndrome |
| US5668114A (en) * | 1996-05-08 | 1997-09-16 | Birkmayer Pharmaceuticals | NADH and NADPH pharmaceuticals for treating hypertension |
| WO2001041732A1 (en) * | 1999-12-06 | 2001-06-14 | Gore Stanley L | Compositions and methods for intranasal delivery of active agents to the brain |
| PT2068825E (en) | 2006-10-04 | 2011-02-11 | M & P Patent Ag | Controlled release delivery system for nasal application of neurotransmitters |
| US8652443B2 (en) | 2008-02-14 | 2014-02-18 | Precision Dermatology, Inc. | Foamable microemulsion compositions for topical administration |
| AR086400A1 (en) | 2011-05-13 | 2013-12-11 | Trimel Pharmaceuticals Corp | FORMULATIONS IN INTRANASAL GEL OF TESTOSTERONE IN DOSE OF LOWER POWER AND USE OF THE SAME FOR THE TREATMENT OF ANORGASMIA OR THE DISORDER OF HYPOACTIVE SEXUAL DESIRE |
| US9757388B2 (en) | 2011-05-13 | 2017-09-12 | Acerus Pharmaceuticals Srl | Intranasal methods of treating women for anorgasmia with 0.6% and 0.72% testosterone gels |
| US20130045958A1 (en) | 2011-05-13 | 2013-02-21 | Trimel Pharmaceuticals Corporation | Intranasal 0.15% and 0.24% testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder |
| US11744838B2 (en) | 2013-03-15 | 2023-09-05 | Acerus Biopharma Inc. | Methods of treating hypogonadism with transnasal testosterone bio-adhesive gel formulations in male with allergic rhinitis, and methods for preventing an allergic rhinitis event |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR6033M (en) | 1967-02-10 | 1968-05-13 | ||
| US4581225A (en) * | 1984-04-25 | 1986-04-08 | Eli Lilly And Company | Sustained release intranasal formulation and method of use thereof |
| NZ222907A (en) * | 1986-12-16 | 1990-08-28 | Novo Industri As | Preparation for intranasal administration containing a phospholipid absorption enhancing system |
| GB8828477D0 (en) * | 1988-12-06 | 1989-01-05 | Riker Laboratories Inc | Medical aerosol formulations |
| DE4003272A1 (en) * | 1990-02-03 | 1991-08-08 | Boehringer Ingelheim Kg | NEW GAS MIXTURES AND THEIR USE IN MEDICINE PREPARATIONS |
| EP0536204B1 (en) * | 1990-06-27 | 1994-04-06 | Minnesota Mining And Manufacturing Company | The use of soluble fluorosurfactants for the preparation of metered-dose aerosol formulations |
| US5116847A (en) * | 1991-01-25 | 1992-05-26 | The Procter & Gamble Company | Use of loperamide and related compounds for treatment of respiratory disease symptoms |
| DE4214953C2 (en) * | 1992-05-06 | 1995-05-18 | Arrowdean Ltd | Medicines to increase testosterone levels |
-
1992
- 1992-06-03 DE DE19924218291 patent/DE4218291A1/en not_active Withdrawn
-
1993
- 1993-05-17 WO PCT/DE1993/000442 patent/WO1993024107A1/en active IP Right Grant
- 1993-05-17 JP JP50007994A patent/JP3705600B2/en not_active Expired - Lifetime
- 1993-05-17 DE DE59301810T patent/DE59301810D1/en not_active Expired - Lifetime
- 1993-05-17 EP EP93909781A patent/EP0643575B1/en not_active Expired - Lifetime
- 1993-05-17 ES ES93909781T patent/ES2085775T3/en not_active Expired - Lifetime
- 1993-05-17 CA CA002135203A patent/CA2135203C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| ES2085775T3 (en) | 1996-06-01 |
| WO1993024107A1 (en) | 1993-12-09 |
| CA2135203A1 (en) | 1993-12-09 |
| JPH07507279A (en) | 1995-08-10 |
| DE59301810D1 (en) | 1996-04-11 |
| JP3705600B2 (en) | 2005-10-12 |
| EP0643575A1 (en) | 1995-03-22 |
| DE4218291A1 (en) | 1993-12-09 |
| EP0643575B1 (en) | 1996-03-06 |
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