GB2443928A - Transdermal pharmaceutical composition comprising Zolpidem - Google Patents
Transdermal pharmaceutical composition comprising Zolpidem Download PDFInfo
- Publication number
- GB2443928A GB2443928A GB0722015A GB0722015A GB2443928A GB 2443928 A GB2443928 A GB 2443928A GB 0722015 A GB0722015 A GB 0722015A GB 0722015 A GB0722015 A GB 0722015A GB 2443928 A GB2443928 A GB 2443928A
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- GB
- United Kingdom
- Prior art keywords
- pyridine
- imidazo
- zolpidem
- use according
- acetamide
- 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.)
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- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 229960001475 zolpidem Drugs 0.000 title claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 3
- 239000000203 mixture Substances 0.000 claims abstract description 27
- NSJOHWXCJYNOSF-UHFFFAOYSA-N 2-imidazo[1,2-a]pyridin-3-ylacetamide Chemical compound C1=CC=CN2C(CC(=O)N)=CN=C21 NSJOHWXCJYNOSF-UHFFFAOYSA-N 0.000 claims abstract description 23
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims abstract description 22
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229960001948 caffeine Drugs 0.000 claims abstract description 11
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims abstract description 11
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- 230000037317 transdermal delivery Effects 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 208000035475 disorder Diseases 0.000 abstract description 2
- 206010051290 Central nervous system lesion Diseases 0.000 abstract 1
- 239000010410 layer Substances 0.000 description 10
- YDHIMEXEGOCNHU-UHFFFAOYSA-N 2-pyridin-3-ylacetamide Chemical compound NC(=O)CC1=CC=CN=C1 YDHIMEXEGOCNHU-UHFFFAOYSA-N 0.000 description 9
- 230000005059 dormancy Effects 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
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- 206010041349 Somnolence Diseases 0.000 description 2
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- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
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- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- QCOZYUGXYJSINC-UHFFFAOYSA-N 1,3,7-trimethylpurine-2,6-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C.CN1C(=O)N(C)C(=O)C2=C1N=CN2C QCOZYUGXYJSINC-UHFFFAOYSA-N 0.000 description 1
- 206010001541 Akinesia Diseases 0.000 description 1
- 208000006373 Bell palsy Diseases 0.000 description 1
- 235000011273 Benincasa Nutrition 0.000 description 1
- 229940122226 Benzodiazepine receptor agonist Drugs 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 208000027104 Chemotherapy-Related Cognitive Impairment Diseases 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
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- 102000005915 GABA Receptors Human genes 0.000 description 1
- 108010005551 GABA Receptors Proteins 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 101000635799 Homo sapiens Run domain Beclin-1-interacting and cysteine-rich domain-containing protein Proteins 0.000 description 1
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- 208000036572 Myoclonic epilepsy Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 206010071323 Neuropsychiatric syndrome Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
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- 208000036826 VIIth nerve paralysis Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 239000000759 benzodiazepine receptor stimulating agent Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000003371 gabaergic effect Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 208000005026 persistent vegetative state Diseases 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
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- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 230000007958 sleep Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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- 150000003892 tartrate 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention relates to transdermal pharmaceutical compositions containing an imidazo [1,2- a ] pyridine-3-acetamide such as Zolpidem. Compositions comprising an imidazo [1,2- a ] pyridine-3-acetamide and caffeine are also disclosed. Claims to the compositions for treating disorders including leukoencephalopathy, obsessive compulsive disorder, brain lesions, cerebral infarct, intracerebral bleeding, Ramsay-Hunt syndrome, ischemic brain damage; and conditions involving strabismus, salivation, muscle spasm, impaired swallowing, smell, or taste, are also included. A further independent claim is included for a composition comprising an imidazo [1,2- a ] pyridine-3-acetamide and caffeine.
Description
TRANSDERMAL THERAPY
The present application relates to the therapeutic substance Zolpidem. More particularly, the present application relates to the transdermal administration of Zolpidem.
Zolpidem, N,N,6-trimethyl-2-(4-methylphenyl)-imidazo[ I,2-a]pyridine-3 -acetamide (N,N,6-tnmethyl-2-p-toylimidazo( I,2,-a)pyridine-3-acetamide), has been described as a selective benzodiazepine receptor agonist, and is commonly prescribed as a sedative and hypnotic drug for the short-term treatment of insomnia. CH3 H3C
it is described in US4382938.
More recently, Benincasa described the use of imidazo[1,2-a]pyridine-3-acetamide derivatives, in particular zolpidem, for the treatment of neuropsychiatric syndromes associated with dysfunction of the neural circuits of the basal ganglia (WO 96/31210). This use was based on the observation that zolpidem prescribed as a sleep-inducing agent improved the symptoms of a patient having Parkinson's disease with obsessive-compulsive disorder and dementia.
Clauss et a!., S. Afr. Med. J. (2000 Jan), 90(l):68-72, subsequently describe a study in which semi-comatose patients were aroused transiently from their permanent vegetative state after application of zolpidem.
Further studies in animals have ascribed this effect to GABA(A) omega-I receptor-specific effects in the primate brain (Clauss et a!., Arznein.-Forsch./Drug Res. (2001) 51(1 1):619-622).
The use of zolpidem in progressive supranuclear palsy is described by Mayr et a!.
(Eur. J. Neurol. (2002) 9(2)3:184-185).
More recently, Clauss and Nel describe the use of zolpidem and related compounds, such as those described in WO 96/31210 having utility in diseases exhibiting diaschisis (WO 2004/100948). The content of WO 2004/100948 is herein incorporated by reference. Other compositions are described in W02004/06693 0, W09 1/03998.
Diaschisis can be described as a sudden loss of function at a site in the brain at a distance from a lesion or site of injury. The term "diaschisis" comes from the Greek meaning "shocked throughout". The concept was first described by von Monakow in 1914, and offers an explanation as to the phenomenon of acute phase central nervous system disorder symptoms which are more extensive and of a different nature to those of the chronic phase.
The mechanism by which diaschisis occurs is not clear.
Various specific pathways of diaschisis have been investigated. One particular example is called crossed cerebellar diaschisis (CCD), first described by Baron in 1980. This finding has been observed subsequently using SPECT perfusion imaging studies of patients having suffered cerebral strokes. Patients have been observed having a decreased blood flow in, inter a/ia, the cerebellum contralateral to the cerebral hemisphere injured by the stroke.
It is postulated that brain injury triggers a set of events that can result in a state of dormancy of normal neuronal tissue at a site close to, or (as in classical diaschisis) removed from the brain injury site, which may be a feature of a neuroprotective reaction of the brain during damage. it is now believed that the majority of brain injuries or brain patho1ogis have associated with them a neural dormancy or diaschisis.
Without wishing to be bound by theory, it is postulated that dormancy or diaschisis results from a structural change or abnormal folding of the GABA receptor molecule; an effect or state which can be reversed by zolpidem's selective GABAergic stimulation of, in particular, the omega I receptors.
WO 2004/100948 describes a study in which brain injured patients exhibiting symptoms of both dormant but viable brain tissue and dead, non-viable brain tissue were administered zolpidem. In such circumstances this was found to result in the reversal of dormancy/diaschisis in viable neuronal tissue. This effect can occur in areas of classical diaschisis and in other areas that may not have previously been recognised (in what can be termed ipsilateral diaschisis etc.).
Zolpidem taken orally has a short half life (approximately 2 to 3 hours). WO 2004/100948 describes oral administration of zolpidem, and the use of a depot for sustained release. It would be desirable, however, to prolong the release profile of administered zolpidem. Indeed, it is acknowledged in WO 2004/100948 that the benefit of zolpidem in brain-injured patients is transient and it occurs for the duration of drug action only.
The present invention is based on the discovery that imidazo[1,2-ct]pyridine-3-acetamides,. such as those described in WO 96/31210, and in particular, zolpidem, can be effectively administered transdermally.
In addition, the present invention is based on the discovery that the therapeutic effect of zolpidem, particularly when used for treating conditions of the brain which exhibit diaschisis and/or dormancy, is enhanced when it is administered with caffeine (1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione).
In a first aspect of the present invention, there is provided a transdermal therapeutic formulation comprising an imidazo[ I,2-a]pyridine-3-acetamide and a carrier.
The imidazo[1,2-u]pyridine-3-acetamide is preferably zolpidem.
The benefits of transdermal delivery include increased patient compliance, localized drug targeting, control over the rate of absorption and the avoidance of reduced bioavailability due to first pass metabolism effects in the liver.
Classic topicalltransdermal delivery vehicles include ointments, creams, lotions, pastes and gels. In an especially advantageous embodiment, the zolpidem is formulated as a transdermal patch; although the formulation of pharmaceuticals in a patch is a well known technology, transdermal patches are not suitable for every pharmaceutical. it had not previously been appreciated that zolpidem could be formulated as a transdermal patch or that such a formulation would provide an effective means of delivery the pharmaceutical. The patch may be a preformed patch containing a single dosage of the imidazo[1,2-a]pyridine-3-acetamide. Alternatively, the patch may be a spray-on patch material, which sets into a patch or film once sprayed onto the skin. In this embodiment, the patch material may be stored in a dispensing device, operable to dispense a single dosage of the imidazo[1,2-a]pyridine-3-acetamide.
The patch may utilise a reservoir system, i.e., the patch comprises an impermeable backing layer, a reservoir containing the active material (e.g. zolpidem) in a suitable solvent, and a rate limiting membrane, which controls diffusion of the active material therethrough to the skin of the patient. The rate limiting membrane may also be adhesive, whereby the patch can be adhered to the skin, or a separate adhesive layer may be provided.
Alternatively, the patch may utilise a matrix system, whereby the active material (e.g. zolpidem) is dispersed or dissolved in a polymer. Such systems may utilise an impermeable backing layer to which a layer of the polymer containing dispersed or dissolved active material may be attached. The polymer layer may be adhesive in itself, or a separate polymer layer may be applied to the polymer layer.
Transdermal patches are known in the art. It is to be appreciated that the present invention is not limited to a particular form of transdermal patch, and that variations may be made to the patch formulation to adjust the rate of API uptake, API dosage, pharmacokinetic properties, pharmacodynamic properties, size, etc., without departing from the principles of present invention.
Reference is made to Figure 1, which is a schematic cross-sectional view of a transdermal patch according to the invention.
In figure 1, a patch generally designated 10 comprises a back layer 12, a reservoir 14 containing an active material, such as zolpidem, in solution, a permeable membrane 16, which controls delivery of the active material to the skin, and adhesive layer 18 which serves to adhere the patch 10 to the skin, and a releasable protective layer 20, which may be peeled away from the other layers when it is desired to apply the patch to the skin of a patient.
In another aspect of the invention, there is provided the use of an imidazo[ I,2-a]pyridine-3-acetamide in the manufacture of a medicament, wherein the medicament is suitable for transdermal administration to a subject in need thereof.
In another aspect of the invention, there is provided a pharmaceutical composition comprising an imidazo[I,2-a]pyridine-3-acetamide and caffeine.
In another aspect of the invention, there is provided the use of an imidazo[ 1,2-a]pyridine-3-acetamide and caffeine in the manufacture of a medicament for the treatment of conditions of the brain which has a lesion andl which or exhibits diaschisis/dormant cells.
Preferably, the imidazo[ 1,2-u]pyridine-3-acetamide is zolpidem.
Administration of zolpidem can result in drowsiness. The combination of zolpidem and caffeine according to the present invention can offset the drowsiness imparted by the zolpidem, thereby improving the functionality of the treatment.
The present invention may be useful for the treatment of conditions of the brain which has a lesion or exhibits diaschisis/dormant cells. Examples of such conditions are described in WO 2004/100948. The invention may help reverse dormancy or diaschisis, or non-functionality induced by ischaemia or post-ischaemia or brain damage, in viable neuronal tissue. This can result in the reversal of brain damage effects. This effect can occur in areas of classical diaschisis and in other areas which may not have previously been recognised as exhibiting diaschisis.
The present invention is of particularly benefit to patients suffering from trauma-induced injury, but who do not exhibit akinesia or tremor, as in Parkinsonism. In particular, the patient may have lost cognition, e.g. have had a cerebellar or cerebral infarct such as in a stroke. The patient may exhibit cortical dysfunction, ataxia, e.g. spinocerebellar ataxia, or other symptoms related to ischaemic injury or brain damage. Other conditions are ruptured brain aneurism and intracerebral bleed. Alternatively or in addition, the patient may exhibit one or more of strabismus, salivation and muscle spasm, or impaired swallowing, smell or taste, or require long-term rehabilitation, e.g. over a period of a month or up to a year or more.
The present invention may also benefit patients suffering from Ramsay-Hunt syndrome, a complication of Herpes Zoster infection. According to some authors, many cases previously described as exhibiting Ramsay- Hunt syndrome, as well as other hitherto unclassified system degenerations associated with myoclonus epilepsy, are examples of myoclonus, epilepsy and ragged red fibres (MERRF).
In addition, patients suffering from vascular and multi-infarct dementia, and Bell's palsy (e.g. of cerebral origin) may be benefited by the present invention.
The invention may lead to increased mobility and functionality in the patient, and the patient may exhibit regeneration.
We have also found that zolpidem may also be used in the treatment of a number of conditions not previously mentioned in the prior art. Thus according to another aspect of the invention, there is provided the use of imidazo[ I,2-a]pyridine-3-acetamide, preferably zolpidem, in the manufacture of a medicament for treating: 1. Chemotherapy or radiation damage to the brain (after radiotherapy-so called radiotherapy fog' and chemo fog').
2. Obsessive Compulsive disorder.
3. Depression.
4. Panic attacks.
5. Central sleep apnoea syndrome.
6. Central auditory impairment The disorders may involve diaschisis andlor dormancy.
We have also found that the administration of zolpidem may be effective to permanently restore dormant cells to normalcy, i.e., previously dormant cells become permanently functional after the administration of zolpidem or other imidazo[1,2-a]pyridine- 3-acetamides.
The dosage of zolpidem administered in the present invention may be any suitable sufficient to have therapeutic effect. Typical dosages may be, for example, from 1 to 100mg per day. The administration may be via transdermal means, eg patch, as described above, or via oral route, such as tablet or sublingual. Sustained release administration is possible either via transdermal or oral route.
The imidazo[ 1,2-a]pyridine-3-acetamide is preferably zolpidem. The imidazo[ 1,2-a]pyridine-3-acetamide may be formulated as a patch, as described above. In addition, the imidazo[ 1,2-a]pyridine-3-acetamide may be formulated with caffeine as described above.
The transdermal formulation may be a conventional transdermal formulation as described in the prior art. Thus the formulation may be provided in the form of a transdermal cream or gel containing the active agent, such as zolpidem or a salt thereof, and any desirable pharmaceutically acceptable carrier. In addition, the formulation may be provided in the form of a transdermal release layer which is coated with, or impregnated with the active agent, such as zolpidem or a salt thereof, and any desirable pharmaceutically acceptable carrier.
In all the above embodiments, the zolpidem may be provided in the form of the tartrate salt, but it is preferably provided in the form of the hemitartrate salt, or a salt having a molecular weight lower than or equal to the molecular weight of the hemitartrate salt.
The compositions according to the invention may also be used in the treatment of patients with auditory impairment (for example hearing loss).
The dosage of zolpidem administered in the present invention may be any suitable sufficient to have therapeutic effect. Typical dosages may be, for example, from 1 to 100mg per day.
In a another aspect of the present invention, there is provided the use of an imidazo[1,2-a]pyridine-3-acetamide in the manufacture of a medicament for treating leukoencephalopathy.
In another aspect of the present invention, there is provided the use of an imidazo[ 1,2-a]pyridine-3-acetamide in the manufacture of a medicament for treating heavy metal poisoning.
The imidazo{1,2-a]pyridine-3-acetamide is preferably zolpidem. The imidazo[1,2-a]pyridine-3-acetamide may be formulated as a patch, as described above. In addition, the imidazo[ I,2-a]pyridine-3-acetamide may be formulated with caffeine as described above.
The transdermal formulation may be a conventional transdermal formulation as described in the prior art. Thus the formulation may be provided in the form of a transdermal cream or gel containing the active agent, such as zolpidem or a salt thereof, and any desirable pharmaceutically acceptable carrier. In addition, the formulation may be provided in the form of a transdermal release layer which is coated with, or impregnated with the active agent, such as zolpidem or a salt thereof, and any desirable pharmaceutically acceptable carrier.
In all the above embodiments, the zolpidem may be provided in the form of the hemitartrate salt, or preferably a lower molecular weight salt.
Claims (28)
- IClaims 1. A transdermal therapeutic formulation comprising an imidazo[ 1,2-a]pyridine-3-acetarnide and a carrier.
- 2. A transdermal therapeutic formulation according to claim 1, wherein the imidazo[ 1,2-a]pyridine-3-acetamide is zolpidem or a pharmaceutically acceptable salt thereof..
- 3. A transdermal therapeutic formulation according to claim 1 or 2, in the form of a transdermal patch.
- 4. A transdermal therapeutic formulation according to claim 1, 2 or 3, further comprising caffeine.
- 5. A transdermal therapeutic formulation according to claim 1, 2, 3 or 4, comprising a release layer coated with, or impregated with, zolpidem or a pharmaceutically accpetable salt thereof.
- 6. A transdermal therapeutic formulation according to any preceding claim, wherein the salt of zolpidem is the hemitartrate salt.
- 7. Use of an imidazo[1,2-a}pyridine-3-acetamide in the manufacture of a medicament, wherein the medicament is suitable for transdermal administration to a subject in need thereof.
- 8. Use according to claim 7, wherein the imidazo[1,2-a]pyridine-3-acetamide is zolpidem or a pharmaceutically acceptable salt thereof.
- 9. Use according to claim 7 or 8, wherein the medicament further comprises caffeine.
- 10. Use according to claim 7, 8 or 9, wherein the medicament is a transdermal patch.S
- 11. Use according to any one of claims 6 to 10, wherein the medicament is for treating: leukoencephalopathy; heavy metal poisoning; chemotherapy or radiation damage to the brain; obsessive compulsive disorder; depression; panic attacks; central sleep apnoea syndrome; central auditory impairment; trauma-induced injury; a cerebellar or cerebral infarct; cortical dysfunction; ataxia; spinocerebellar ataxia; ruptured brain aneurism; intracerebral bleeding; or Ramsay-Hunt syndrome.
- 12. Use according to any one of claims 6 to 10, wherein the subject of treatment exhibits a condition selected from strabismus, salivation, muscle spasm and impaired swallowing, smell or taste, hearing or speaking, or requires long-term rehabilitation.
- 13. Use according to any one of claims 6 to 10, wherein the subject of treatment has lost cognition.
- 14. Use according to any one of claims 6 to 10, wherein the subject of treatment has a condition which is ischaemic or post-ischaemic, or brain damage.
- 15. Use according to any one of claims 6 to 14, wherein the subject has a condition of the brain which has a lesion.
- 16. Us according to claim 15, wherein the condition is such that the brain also exhibits and diaschisis/dormant cells.
- 17. A composition comprising an imidazo[ 1,2-a]pyridine-3-acetamide and caffeine.
- 18. A composition according to claim 17, wherein the imidazo[1,2-a]pyridine-3-acetamide is zolpidem, or a salt thereof.
- 19. A composition according to claim 17 or 18, suitable for transdermal delivery of said imidazo{1,2-a]pyridine-3-acetamide to a subject in need thereof.
- 20. A composition according to claim 19 in the form of a transdermal patch.
- 21. Use of an imidazo[1,2-a]pyridine-3-acetamide and caffeine in the manufacture of a medicament.
- 22. Use according to claim 21, for the treatment of a condition of the brain which has a lesion.
- 23. Use according to claim 22, wherein the condition is such that the brain also exhibits diaschisis/dorinant cells.
- 24. Use according to any one of claims 21 to 23, wherein the medicament is for treating: leukoencephalopathy; heavy metal poisoning; chemotherapy or radiation damage to the brain; obsessive compulsive disorder; depression; panic attacks; central sleep apnoea syndrome; central auditory impainnent; trauma-induced injury; a cerebellar or cerebral infarct; cortical dysfunction; ataxia; spinocerebellar ataxia; ruptured brain aneurism; intracerebral bleeding; or Ramsay-Hunt syndrome.
- 25. Use according to any of one claims 21 to 23, wherein the subject of treatment exhibits a condition selected from strabismus, salivation, muscle spasm and impaired swallowing, smell or taste, hearing or speaking, or requires long-term rehabilitation.
- 26. Use according to any one of claims 21 to 23, wherein the subject of treatment has lost cognition.
- 27. Use according to any one of claims 21 to 23, wherein the subject of treatment has a condition which is ischaemic or post-ischaemic, or brain damage.
- 28. Use according to any one of claims 21 to 27, wherein the imidazo[1,2-a]pyridine-3-acetamide is zolpidem. or a pharmaceutically acceptable salt thereof
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0622285A GB0622285D0 (en) | 2006-11-08 | 2006-11-08 | Transdermal therapy |
| GB0705689A GB0705689D0 (en) | 2007-03-21 | 2007-03-21 | Therapeutic applications of Zolpidem |
Publications (2)
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|---|---|
| GB0722015D0 GB0722015D0 (en) | 2007-12-19 |
| GB2443928A true GB2443928A (en) | 2008-05-21 |
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| GB0722015A Withdrawn GB2443928A (en) | 2006-11-08 | 2007-11-08 | Transdermal pharmaceutical composition comprising Zolpidem |
Country Status (2)
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| GB (1) | GB2443928A (en) |
| WO (1) | WO2008056139A2 (en) |
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| GB0809936D0 (en) * | 2008-05-30 | 2008-07-09 | Regen Therapeutics Plc | Therapeutic use of zolpidem |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991003998A1 (en) * | 1989-09-14 | 1991-04-04 | Cygnus Research Corporation | Transdermal delivery device having delayed onset |
| WO1996031210A1 (en) * | 1995-04-07 | 1996-10-10 | Clarendon-Trading & Investimentos Lda | USE OF IMIDAZO[1,2-a]PYRIDINE-3-ACETAMIDE DERIVATIVES FOR THE THERAPEUTIC TREATMENT OF NEUROPSYCHIATRIC SYNDROMES ASSOCIATED WITH DISFUNCTION OF THE NEURAL CIRCUITS OF THE BASAL GANGLIA |
| WO2004066930A2 (en) * | 2003-01-27 | 2004-08-12 | Arthur Zaks | Method for inducing pain relief using imidazo[1,2-a]pyridine derivatives |
| WO2004100948A1 (en) * | 2003-05-19 | 2004-11-25 | Sciencom Ltd | Further therapeutic use of zolpidem |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7632517B2 (en) * | 1997-10-01 | 2009-12-15 | Novadel Pharma Inc. | Buccal, polar and non-polar spray containing zolpidem |
| EP1005863A1 (en) * | 1998-12-04 | 2000-06-07 | Synthelabo | Controlled-release dosage forms comprising a short acting hypnotic or a salt thereof |
| US20030104041A1 (en) * | 1999-12-16 | 2003-06-05 | Tsung-Min Hsu | Transdermal and topical administration of drugs using basic permeation enhancers |
| AU3104301A (en) * | 2000-01-20 | 2001-07-31 | Noven Pharmaceuticals, Inc. | Compositions and methods to effect the release profile in the transdermal administration of active agents |
| US20040139705A1 (en) * | 2000-03-14 | 2004-07-22 | Noven Pharmaceuticals, Inc. | Packaging materials for transdermal drug delivery systems |
| US6635274B1 (en) * | 2000-10-27 | 2003-10-21 | Biochemics, Inc. | Solution-based transdermal drug delivery system |
| GB0329918D0 (en) * | 2003-12-24 | 2004-01-28 | West Pharm Serv Drug Res Ltd | Intranasal compositions |
| TW200616589A (en) * | 2004-10-08 | 2006-06-01 | Noven Pharma | Transdermal delivery of drugs based on crystal size |
| WO2006044206A2 (en) * | 2004-10-08 | 2006-04-27 | Noven Pharmaceuticals, Inc. | Transdermal drug delivery device including an occlusive backing |
-
2007
- 2007-11-08 GB GB0722015A patent/GB2443928A/en not_active Withdrawn
- 2007-11-08 WO PCT/GB2007/004245 patent/WO2008056139A2/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991003998A1 (en) * | 1989-09-14 | 1991-04-04 | Cygnus Research Corporation | Transdermal delivery device having delayed onset |
| WO1996031210A1 (en) * | 1995-04-07 | 1996-10-10 | Clarendon-Trading & Investimentos Lda | USE OF IMIDAZO[1,2-a]PYRIDINE-3-ACETAMIDE DERIVATIVES FOR THE THERAPEUTIC TREATMENT OF NEUROPSYCHIATRIC SYNDROMES ASSOCIATED WITH DISFUNCTION OF THE NEURAL CIRCUITS OF THE BASAL GANGLIA |
| WO2004066930A2 (en) * | 2003-01-27 | 2004-08-12 | Arthur Zaks | Method for inducing pain relief using imidazo[1,2-a]pyridine derivatives |
| WO2004100948A1 (en) * | 2003-05-19 | 2004-11-25 | Sciencom Ltd | Further therapeutic use of zolpidem |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0722015D0 (en) | 2007-12-19 |
| WO2008056139A3 (en) | 2008-10-02 |
| WO2008056139A2 (en) | 2008-05-15 |
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