WO2008036858A2 - Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief - Google Patents
Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief Download PDFInfo
- Publication number
- WO2008036858A2 WO2008036858A2 PCT/US2007/079097 US2007079097W WO2008036858A2 WO 2008036858 A2 WO2008036858 A2 WO 2008036858A2 US 2007079097 W US2007079097 W US 2007079097W WO 2008036858 A2 WO2008036858 A2 WO 2008036858A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- anesthetic
- solution
- pain
- container
- composition
- Prior art date
Links
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
- A61K31/02—Halogenated hydrocarbons
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A61P23/02—Local anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- the present invention relates generally to the fields of anesthesia and pain management. More specifically, the present invention provides methods for reducing pain by regionally delivering a solution comprising a volatile anesthetic to a subject in need of pain reduction or anesthesia.
- the pain may be minor, such as headaches, acute lower back pain, and acute muscle pain, or severe, such as chronic pain.
- Chronic pain may be associated with cancer treatment, HIV, diabetes, or other conditions.
- Chronic pain can be difficult to treat, with many chronic pain sufferers noting that their pain is not well controlled with current pain medications or that their medications have significant associated adverse effects (e.g., nausea and vomiting, dependence, tolerance, etc.).
- intrathecal infusion pumps and neurostimulators have been developed.
- Intrathecal infusion pumps are aimed at continuous, or near continuous delivery of liquid anesthetic and/or analgesic agents. Many of these infusion pumps are totally implantable, which helps to reduce the risk of infection when compared to the long-term use of external systems.
- the infusion pump may also be programmable to allow patients or their clinicians to adjust dosing amounts or daily delivery schedule, helping to meet a patient's changing needs.
- Neurostimulators are available in various forms and stimulate nerves to relieve pain. Both intrathecal pumps and neurostimulators have drawbacks, including the onset of tolerance, with the treatments becoming less effective over time. In addition, neither intrathecal infusion pumps nor neurostimulators are suitable for anesthetizing a patient prior to a surgery.
- anesthesia Various approaches for inducing anesthesia or analgesia are known. Delivery of a general anesthetic renders a patient unconscious and unaware of the surgery. In contrast, anesthetics may be applied regionally, for example, to the spine, epidurally, or near a nerve in a nerve block to anesthetize only a portion of the patient's body. For general anesthesia, delivery of a general anesthetic to a patient prior to surgery is typically performed using an initial i.v. injection of an anesthetic followed by intubation and administration of an inhalable anesthetic gas. It is worthwhile to note that the mechanism of action for general anesthesia is still not completely understood.
- the present invention overcomes limitations in the prior art by providing new methods for administering anesthetics and reducing pain in a subject, such as a human or animal patient or laboratory animal such as a mouse or rat, in need of such pain reduction.
- the methods preferably comprise the local or regional delivery, such as intrathecal or epidural delivery, of a volatile anesthetic in an aqueous based solution to the subject in an amount effective to reduce chronic or acute pain.
- the anesthetic may be delivered to the subject to anesthetize the subject prior to a surgery.
- pain reduction is intended to cover pain reduction as a result of anesthesia, analgesia, and/or the inhibition of neural impulses involved in pain perception, e.g., via partial nerve conduction block.
- the present invention has several substantial advantages over previously used methods for regional anesthesia. These advantages include: (1) the volatile anesthetics of the present invention are rapidly titratable, thus administration of a volatile anesthetic according to the present invention can result in a very quick onset of analgesia or regional anesthesia. (2) The present invention allows for the quick dissipation of anesthetics after administration; thus the anesthesia or analgesia may be rapidly ended. These properties are of particular value to a practitioner, as it may be desirable for a practitioner to quickly alter the dosing of a regional anesthesia or analgesia as desired.
- the volatile anesthetics of the present invention are generally non-opioid compounds, which provides various benefits for a practitioner, as opioids possess certain disadvantages, including tolerance, drug interactions, and dependence etc.
- An aspect of the present invention relates to a method for reducing pain in a subject in need of such pain reduction comprising regionally or locally delivering to the subject a volatile anesthetic dissolved in a solution in an amount effective to reduce pain.
- the anesthetic is delivered by routes other than intravenously in that intravenous delivery could potentially give rise to general anesthesia that, while not specifically excluded from the present invention, is not a preferred aspect.
- Preferred volatile anesthetics are the halogenated ether anesthetic dissolved in an aqueous, pharmaceutically acceptable solution.
- the anesthetic may preferably be delivered intrathecally, epidurally, or in a nerve block procedure, to relieve, for example, chronic pain or acute pain.
- a volatile anesthetic in solution is delivered to anesthetize a portion of the subject prior to a surgery.
- the volatile anesthetic is a halogenated volatile anesthetic selected from the group consisting of isoflurane, halothane, enflurane, sevoflurane, desflurane, methoxyflurane, and mixtures thereof, with isoflurane being particularly preferred.
- the solution such as an isoflurane solution, may be prepared in a concentration of about 5 ng/ml solution to about 100 ng/ml solution.
- the solution may comprise from about 5% to about 75% v/v, from about 10% to about 50% v/v, or about 10% v/v anesthetic in solution.
- the anesthetic may be isoflurane and/or the solution may be artificial cerebrospinal fluid.
- the delivery of the active agent may be continuous, periodic, a one-time event, or the active agent may be both periodically administered and continuously administered to the subject on separate occasions.
- the reduction may comprise elimination of pain perception of a portion of the body of the subject.
- the aqueous solution comprising the volatile anesthetic is sterile.
- the nature of the solution is not believed to be critical, and solutions such as normal saline or even solutions formulated to mimic natural body fluids, such as artificial cerebrospinal fluids, are contemplated.
- Yet another aspect of the present invention involves a sealed container comprising an anesthetic solution of the present invention.
- the interior of the container may be sterile.
- the container may comprise a rubber stopper which can be easily pierced by an injection needle.
- the container may comprise the chamber portion of a syringe.
- the container may comprise a drip chamber.
- the drip chamber may be coupled to a catheter.
- the catheter may be an epidural catheter or an intrathecal catheter.
- the container may be a plastic bag, a glass bottle, or a plastic bottle.
- the container may be coupled to an infusion pump.
- the infusion pump may be an intrathecal pump, an epidural delivery infusion pump, or a patient control analgesia (PCA) pump.
- PCA patient control analgesia
- the infusion pump may be programmable.
- the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), "including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.
- FIG. 1 A flowchart representing a general method for delivering an anesthetic gas to a subject.
- FIG. 2 Inhibition of pain via intrathecal administration of isoflurane solution as measured using the hotplate test.
- FIG. 3 Inhibition of pain using intrathecal isoflurane in artificial cerebrospinal fluic (ACSF). The time course for paw withdrawal from a hotplate after administration of isoflurane- ACSF, at a dose of 1.46 mg isoflurane, is shown.
- FIG. 4 A stimulus response (SR) graph is shown of the maximal possible effect (MPE) by dose for the time point of 10 minutes after intrathecal injection of isoflurane-ACSF.
- the present invention provides methods for reducing pain in a subject in need of such pain reduction.
- volatile anesthetics are normally inhaled during a general anesthesia procedure
- the inventors have discovered that volatile anesthetics may be dissolved in a solution and delivered regionally or locally (e.g., intrathecally, epidurally, or in a nerve block) to inhibit or block pain perception.
- the methods may involve the delivery of a halogenated ether anesthetic to the subject in an amount effective to reduce pain.
- the present invention may be used for pain management of chronic or acute pain.
- the anesthetic may be delivered to a subject to anesthetize at least a portion of the subject prior to a surgery.
- the halogenated ether anesthetics or volatile anesthetics suitable for use with the described methods include agents which, although often liquid at room temperature, are capable of easily being becoming gaseous or are already gaseous at room temperature and can reduce pain, e.g., without significant side effects. It may be desirable, for example, to select an anesthetic that is minimally metabolized by the body or is otherwise inert. In this way, liver and kidney toxicity may be minimized. Similarly, it may be desirable for the anesthetic to have a short half-life, or be fast acting to promote titratability (i.e., the subject can easily adjust the delivery amount for the amount of pain he or she is experiencing). An active agent gas that does not produce tolerance (unlike opioids or local anesthetic agents) or dependence (like opioids) may also be desirable.
- Volatile anesthetics are a well known class of anesthetics which includes halogenated ether compounds, isoflurane, sevoflurane, halothane, enflurane, desflurane, methoxyflurane, and diethyl ethers. In certain embodiments xenon may also be used with the present invention. A single anesthetic or mixtures of the above anesthetics may be particularly suitable for use with the methods described herein.
- a gas anesthetic may be used with the present invention.
- the gas anesthetic may be dissolved in a solution according to the present invention and administered in a regional or local anesthesia procedure, such as an epidural, intrathecal, or nerve block procedure.
- Gas anesthetics other than halogenated anesthetics are contemplated, and examples or which include xenon, nitrous oxide, cyclopropane, and ether.
- other biologically active gases e.g., nitric oxide, etc.
- More than one anesthetic may be administered at one time, and different anesthetics may be administered at various times throughout a single treatment cycle. For example, 2, 3, 4 or more anesthetic agents may be simultaneously or repeatedly administered to a subject. When compounds are repeatedly administered to a subject, the duration between administration of compounds may be about 1-60 seconds, 1-60 minutes, 1-24 hours, 1-7 days, 1-6 weeks or more, or any range derivable therein. In some instances, it may be desirable to stage the delivery of different halogenated ether compounds depending on their physical and physiological properties.
- the amount of the anesthetic to be administered depends on the particular indication desired.
- the dose will depend on the type of pain intended to be treated.
- the dose may be different, for instance, if the delivery of the anesthetic is intended to reduce chronic pain as opposed to acute pain.
- the dose may be different if the active agent will be used to anesthetize a subject (locally or generally).
- the subject's physical characteristics may also be important in determining the appropriate dosage. Characteristics such as weight, age, and the like may be important factors.
- the anesthetic may have increased potency with age, as has been demonstrated in the case of the volatile anesthetic isoflurane.
- the temperature of the volatile anesthetic may also be considered as a factor in selecting an appropriate dose, as the solubility of many anesthetics may be affected by the temperature of the anesthetic and/or aqueous solution. For example, increases in temperature may increase the solubility, and thus potency, of the active agent; this property has been demonstrated with certain anesthetic agents.
- the particular dosage may also be dependent on the dosing regime chosen. For example, the active agent may be delivered continuously or periodically. Conversely, the active agent may be administered as a single administration as a one-time event.
- Volatile anesthetics e.g., halogenated anesthetic compounds
- a halogenated anesthetic or volatile anesthetic may be administered to achieve cerebrospinal fluid (CSF) concentration of from about 5 to about 500,000 nanograms/ml.
- CSF cerebrospinal fluid
- the dose range will vary depending on the compound selected and patient variability, it is generally true that lower doses such as from about 0.01 to about 10,000 nanogram/ml are more suitable for treating minor to moderate pain, while higher doses such as from about 10000 nanogram/ml to about 500,000 nanogram/ml or more are suitable for treating severe pain and inducing anesthesia.
- the doses may be given once (for a minor single occurrence of pain), repeatedly (for moderate or chronic pain), or continuously (for severe pain or anesthesia purposes). Combinations of these dosing regimes may also be used. For example, a subject suffering from severe pain may require continuous dosing with periodic additional dosing needed for breakthrough pain.
- an anesthetic e.g., a volatile anesthetic, isoflurane, etc.
- a solution such as saline or an artificial CSF solution
- concentration of the volatile anesthetic may vary.
- a solution may contain an anesthetic in a v/v ratio of from about 1 to about 99%, from about 10 to about 75%, from about 10 to about 50%, from about 20 to about 50%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about 20%, about 15%, about 10%, about 5% or any range derivable therein.
- the anesthetic may be a volatile anesthetic, such as isoflurane
- the solution may be an artificial cerebrospinal fluid (ACSF) solution.
- ACSF cerebrospinal fluid
- a solution of about 10% volatile anesthetic such as isoflurane, may be used; this solution may be administered as a bolus injection, continuously, and/or repeatedly to achieve analgesia and/or anesthesia.
- a 10% v/v solution of a volatile anesthetic may be used to induce analgesia.
- Higher concentrations of volatile anesthetic may be used, in various embodiments, to induce a regional anesthesia.
- Anesthetics of the present invention may be delivered regionally or locally.
- "Regional” or “local” anesthesia is distinct from general anesthesia and refers to anesthetic procedures which allow for the preferential delivery of an anesthetic to a specific region of the body, such as near a nerve or a nerve bundle.
- general anesthesia allows for the systemic administration of an anesthetic, e.g., via intravenous administration.
- Regional or local anesthesia typically allows for a lower total body concentration (although elevated local concentrations) of an anesthetic to be administered to a subject for analgesia or diminished pain perception of at least a portion of the subject's body.
- intrathecal anesthesia, epidural anesthesia, and nerve blocks are examples of regional or local anesthesia.
- Specific concentrations of anesthetics which may be used for regional or local anesthesia include from about 250 to about 50,000 nanogram/ml, from about 250 to about 25000 nanogram/ml, from about 250 to about 10000 nanogram/ml, from about 250 to about 5000 nanogram/ml, from about 250 to about 2500 nanogram/ml, or from about 250 to about 1000 nanogram/ml.
- the present invention may be used with various nerve block procedures.
- Nerve block procedures according to the present invention may be performed with or without ultrasound visualization; for example, an ultrasound machine may be used to visualize the region of the body involved a the nerve block procedure, such as, e.g., various nerve bundles in the shoulder, neck, lower back, etc.
- an ultrasound machine may be used to visualize the region of the body involved a the nerve block procedure, such as, e.g., various nerve bundles in the shoulder, neck, lower back, etc.
- the inventors envision that the present invention may be used in conjunction with a hip replacement, shoulder replacement, and/or birthing-related procedures.
- compositions and methods of the present invention may be used for pain management.
- Pain management is distinct from general anesthesia in that a lower total body concentration of an anesthetic may be administered to a subject to in order to increase analgesia or decrease perception of pain, preferably without rendering the subject unconscious.
- Specific concentrations of anesthetics which may be used for pain management include from about 250 to about 50,000 nanogram/ml, from about 250 to about 25000 nanogram/ml, from about 250 to about 10000 nanogram/ml, from about 250 to about 5000 nanogram/ml, from about 250 to about 2500 nanogram/ml, or from about 250 to about 1000 nanogram/ml.
- Epidural or intrathecal administration of an anesthetic may be accomplished via techniques known in the art, such as the use of an intrathecal or epidural catheter.
- the catheter should be placed closer to the nerves critical for the propagation of any pain sensory information which the practitioner desires to inhibit, without damaging the nerves.
- routes of administration include: injection, infusion, continuous infusion, localized perfusion bathing target cells directly, via a catheter, via nanoparticle delivery, topical administration (e.g., in a carrier vehicle, a topical control release patch), intra-articular, intravenous and/or oral administration.
- topical administration e.g., in a carrier vehicle, a topical control release patch
- intra-articular e.g., in a carrier vehicle, a topical control release patch
- intra-articular e.g., in a carrier vehicle, a topical control release patch
- intra-articular e.g., in a carrier vehicle, a topical control release patch
- intra-articular e.g., in a carrier vehicle, a topical control release patch
- intra-articular e.g., in a carrier vehicle, a topical control release patch
- intravenous and/or oral administration e.g., in a carrier vehicle, a topical control release patch
- anesthetics of the present invention are not administered intravenously.
- Intravenous administration is often used for general anesthesia (Mathias et al. 2004) and typically results in the rapid distribution of the anesthetic agent throughout the body of a subject.
- intravenous administration is incompatible for use with regional or local anesthesia.
- FIG. 1 provides a flowchart depiction of a general method for delivering a halogenated ether anesthetic.
- method (100) begins with the selection of an halogenated ether compound (102).
- the halogenated ether anesthetic may be a standard volatile anesthetic gas, or an active agent that is capable or reducing pain and of becoming readily gaseous, as described above.
- a halogenated ether anesthetic After a halogenated ether anesthetic has been selected, it may be dissolved into a solution (104).
- the solution may be an aqueous solution, such as saline, artificial cerebrospinal fluid, the subject's own cerebrospinal fluid, or the like. In some variations, other solutions may be appropriate.
- the saline may be lactated Ringer's solution, acetated Ringer's solution, phosphate buffered saline (PBS), Dulbecco's phosphate buffered saline (D-PBS), Tris-buffered saline (TBS), Hank's balanced salt solution (HBSS), or Standard saline citrate (SSC).
- PBS phosphate buffered saline
- D-PBS Dulbecco's phosphate buffered saline
- TBS Tris-buffered saline
- HBSS Hank's balanced salt solution
- SSC Standard saline citrate
- the saline solutions of the present invention are, in certain embodiments, "normal saline” (i.e., a solution of about 0.9% w/v of NaCl).
- Normal saline has a slightly higher degree of osmolality compared to blood; however, in various embodiments, the saline may be isotonic in the body of a subject such as a human patient.
- Normal saline (NS) is often used frequently in intravenous drips (IVs) for patients who cannot take fluids orally and have developed severe dehydration.
- half-normal saline i.e., about 0.45% NaCl
- quarter-normal saline i.e., about 0.22% NaCl
- about 5% dextrose or about 4.5 g/dL of glucose may be included in the saline.
- one or more salt, buffer, amino acid and/or antimicrobial agent may be included in the saline.
- ACSF cerebrospinal fluid
- the ACSF is a buffered salt solution (pH 7.4) with the following composition (in mM): NaCl, 120; KCl, 3; NaHCO 3, 25; CaCl 2 , 2.5; MgCl 2 , 0.5; glucose, 12.
- ACSF can also be obtained from various commercial sources, such as from Harvard Apparatus (Holliston, Massachusetts ).
- a preservative or stabilizer may be included in the composition or solution.
- the prevention of the action of microorganisms can be brought about by preservatives such as various antibacterial and antifungal agents, including but not limited to parabens (e.g., methylparabens, propylparabens), chlorobutanol, phenol, sorbic acid, thimerosal or combinations thereof.
- Agents which may be included suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions (U.S. Patent 5,466,468, specifically incorporated herein by reference in its entirety). In all cases the composition is preferably sterile and must be fluid to facilitate easy injectability.
- Solutions are preferably stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms, such as bacteria and fungi.
- stabilizers which may be included include buffers, amino acids such as glycine and lysine, carbohydrates such as dextrose, mannose, galactose, fructose, lactose, sucrose, maltose, sorbitol, mannitol, etc. Appropriate stabilizers or preservatives may be selected according to the route of administration desired.
- the weight ranges of compounds in the solution may vary.
- the composition may comprise about 1-5 wt% anesthetic agent, about 1-5 wt% preservative/stabilizer, about 1-5 wt% NaCl, and about 85%-97% water.
- the ratio of anesthetic to water may be varied as needed to achieve the desired effect (pain reduction or analgesia, regional anesthesia, etc.).
- the solution and/or composition may also be sterilized prior to administration.
- Methods for sterilization are well known in the art and include heating, boiling, pressurizing, filtering, exposure to a sanitizing chemical ⁇ e.g., chlorination followed by dechlorination or removal of chlorine from solution), aeration, autoclaving, and the like.
- the active agent gas may be dissolved into the solution in any number of ways. For example, it may be bubbled through the solution, e.g., using a vaporizer, or it may be solubilized by agitation.
- an anesthetic such as a halogenated ether or a volatile anesthetic may be measured in liquid form and directly admixed into a solution.
- other suitable methods of dissolving the anesthetic into solution may also be used.
- the halogenated ether anesthetic After the halogenated ether anesthetic has been solubilized, it may be administered to a subject in need of pain reduction (including pain reduction in the form of anesthesia) epidurally or intrathecally (FIG.
- a volatile anesthetic is admixed with a solultion in a closed vacuum container, and the combined solutions are then mechanically agitated for 3-5 minutes and held in a thermo-neutral sonicator until use.
- solutions of the present invention are essentially free of oil-in- water emulsions such as soybean emulsion.
- Oil-in-water emulsions may alter the pharmacokinetics and/or distribution of an anesthetic, which may not be desirable in certain instances. Additionally, in various embodiments, oil-in-water emulsions are not desirable for intrathecal or epidural applications, as a practitioner may not wish to inject oil into the spinal canal.
- Saline, artificial CSF, or the patients own CSF may be used for intrathecal or epidural administration of an anesthetic according to the present invention. Lipid emulsions also have other drawbacks and risks.
- lipid emulsions can cause pain and irritation upon injection.
- Lipid emulsions also pose a not insubstantial risk of infection, as has been observed in the past with bacterially contaminated propofol emulsions.
- the present invention addresses these limitations by providing solutions which can reduce pain perception upon injection and may have a reduced risk of contamination.
- compositions of the present invention comprise an effective amount of one or more anesthetic or biologically active gas or additional agent dissolved or dispersed in a pharmaceutically acceptable carrier.
- pharmaceutically acceptable refers to molecular entities and compositions that do not produce an adverse, allergic or other untoward reaction when administered to an animal, such as, for example, a human, as appropriate.
- the preparation of an pharmaceutical composition that contains at least one anesthetic or biologically active gas in solution or additional active ingredient will be known to those of skill in the art in light of the present disclosure, as exemplified by Remington: The Science and Practice of Pharmacy, 20th Edition (2000), which is incorporated herein by reference.
- preparations should meet sterility, pyrogenicity, general safety and purity standards as required by FDA Office of Biological Standards. Examples
- This study was designed to evaluate efficacy of direct intrathecal injection of anesthetic agent gases in reducing pain and providing analgesia.
- the study was conducted over a one (1) month period using anesthetic gases isoflurane and sevoflurane injected directly intrathecally or dissolved in saline as shown in the studies below.
- the subject animal used was the rat, since the rat has a well-established model of pain/analgesia testing.
- Sprague-Dawley rats weighing over 350gm were used. The rats were anesthetized with pentobarbital (50mg/kg), and the anesthetic depth of the animals was determined by corneal reflex and paw withdrawal reflex to a noxious stimulus.
- the neck of the rats were shaved and cleaned with disinfectant solutions in order to avoid bacterial contamination during surgery.
- a midline surgical dissection of the posterior neck muscles was performed to obtain access to the occipito-atlantoid membrane. This membrane was identified and then dissected.
- a sterile polyethylene catheter was introduced in the subarachnoid space until the lumbar enlargement of the spinal cord (approximately 7-8cm measured in each animal). The surgical wound was closed, first suturing the neck muscles with 3-0 silk sutures and then closing the skin incision with staples.
- Isoflurane (l-chloro-2,2,2-trifluoroethyl difluoromethyl ether) and sevoflurane (fluoromethyl 2, 2, 2-trifluoro-l-(trifluoromethyl) ethyl ether) were used as the halogenated ether compounds. Both of these are halogenated volatile anesthetic agents, with isoflurane manufactured by Baxter and sevoflurane manufactured by Abbott Laboratories. The 12 rats were divided into 3 groups of four rats each for study A and B.
- a "hotplate” behavioral test was used to evaluate pain perception and analgesia.
- the pain behavioral testing model used in these studies have been well established by Tony Yaksh. (See, e.g. Chaplan et al., 1994; Yaksh et al., 2001 ; Kim and Chung, 1992; Sorkin et al., 2001). This test involves determining how quickly a rat will withdraw its hind paw in response to a noxious stimulus such as a radiant heat source placed directly underneath its paw. This time for withdrawal is known as "thermal withdrawal latency".
- Rats were transferred for testing onto a modified Hargreaves apparatus with a heated glass plate maintained at 25°C (see Hargreaves et al., 1988). A focused projection bulb below the plate was aimed at the mid-plantar surface of the paw. A photodiode-activated timer measured the withdrawal latency, and a cutoff time of 25 seconds was used to prevent tissue damage. Thermal withdrawal latency to radiant heat was measured at 5 minutes and 30 minutes after each intrathecal injection. Each paw was tested three times, and the results were averaged. The below data was collected for both the right and left hind paws:
- Group 1 Control Group (Normal Saline) Tested at 5 minutes
- Test 1 Test 2 Test 3 Averase
- Test 1 Test 2 Test 3 Averase
- Test 1 Test 2 Test 3 Averase
- Rat 11 10.05 8.44 9.32 11.74 7.66 6.13 8.89
- Isoflurane was dissolved into saline using the following method (also referred to as the "bubbling" method).
- Study C A mock vaporizing device was created using a 500 ml modified Erlenmeyer flask (2 inlets and 1 catheter into the liquid phase). The flask was partially filled with 0.9% normal saline and a stoppered glass pipette was inserted into the bottom of the liquid phase for injection of isoflurane. A second egress pipette allowed egress of gas from the closed container. 2% isoflurane solution in oxygen at 2 L/min was injected through the pipette, saturating the 0.9% saline solution after approximately 10 minutes of injection. 5 mL was drawn from the saturated saline solution and administered to 10 animals using the procedures outlined in Example I above.
- Study C Data is presented here: in seconds to paw withdrawl to heat source. Table and graphic format. Results are shown in FIG. 2.
- Pain sensitivity was measured after intrathecal administration of isoflurane in artificial cerebrospinal fluid (ACSF). Further, as detailed below, the isoflurane was first dissolved in ACSF and then sonicated before administration. The dose response relationship was then evaluated by generating a stimulus-response (SR) graph in order to determine relevant concentrations of isoflurane that may be administered intrathecally to achieve analgesia or anesthesia.
- SR stimulus-response
- the characterization of the pharmacological profile of intrathecal administration of isoflurane in ACSF was performed in this example using rats; further, as would be appreciated by one of skill in the art, analogous approaches may be used to determine the precise pharmacological profile in humans.
- Isoflurane dissolved in ACSF was prepared by the following method. Isoflurane was admixed in a closed vacuum container in a v/v ratio of 10-50% with buffered salt solution that approximates cerebrospinal fluid (pH 7.4) with the following composition (in mM): NaCl, 120; KCl, 3; NaHCO 3, 25; CaCl 2 , 2.5; MgCl 2 , 0.5; glucose, 12. The combined solutions were mechanically agitated for 3-5 min and then held in a thermo-neutral sonicator until use.
- Treatment solution is delivered via intrathecal catheter that overlies lumbar segment Ll -2 in a volume of lO ⁇ l followed by a lO ⁇ l flush of ACSF.
- the "hotplate” behavioral test involves testing the hind paw withdrawal threshold to radiant heat (i.e., duration of time between before a rat to lifts a paw away from a heat source).
- Intrathecal administration of isoflurane in ACSF resulted in analgesia.
- intrathecal administration of isoflurane in ACSF i.e., at a 1.46 mg dose of isoflurane
- a 10 ⁇ L solution of isoflurane in ACSF (10% v/v) was used.
- this dose of isoflurane represents a moderate dose of intrathecal isoflurane.
- FIG. 4 shows an stimulus-response (SR) graph of the maximal possible effect (MPE) by dose for the time point of 10 minutes after the injection of isoflurane in ACSF.
- MPE maximal possible effect
- compositions and methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Anesthesiology (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Materials For Medical Uses (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP07842927.1A EP2081562B1 (en) | 2006-09-20 | 2007-09-20 | Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief |
DK07842927.1T DK2081562T3 (en) | 2006-09-20 | 2007-09-20 | Method of administering volatile anesthetics for regional anesthesia and / or pain relief |
CA2663857A CA2663857C (en) | 2006-09-20 | 2007-09-20 | Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief |
JP2009529406A JP2010504359A (en) | 2006-09-20 | 2007-09-20 | Method for delivering volatile anesthetics for local anesthesia and / or pain relief |
AU2007299738A AU2007299738B2 (en) | 2006-09-20 | 2007-09-20 | Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief |
ES07842927.1T ES2573253T3 (en) | 2006-09-20 | 2007-09-20 | Methods for the supply of volatile anesthetics for regional anesthesia and / or pain relief |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US84629306P | 2006-09-20 | 2006-09-20 | |
US60/846,293 | 2006-09-20 | ||
US94721907P | 2007-06-29 | 2007-06-29 | |
US60/947,219 | 2007-06-29 |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2008036858A2 true WO2008036858A2 (en) | 2008-03-27 |
WO2008036858A3 WO2008036858A3 (en) | 2008-08-07 |
Family
ID=39092912
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2007/079097 WO2008036858A2 (en) | 2006-09-20 | 2007-09-20 | Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief |
Country Status (9)
Country | Link |
---|---|
US (3) | US20080119820A1 (en) |
EP (1) | EP2081562B1 (en) |
JP (4) | JP2010504359A (en) |
AU (1) | AU2007299738B2 (en) |
CA (1) | CA2663857C (en) |
DK (1) | DK2081562T3 (en) |
ES (1) | ES2573253T3 (en) |
PL (1) | PL2081562T3 (en) |
WO (1) | WO2008036858A2 (en) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009094459A1 (en) * | 2008-01-22 | 2009-07-30 | The Board Of Regents Of The University Of Texas System | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief |
WO2010025505A1 (en) * | 2008-09-04 | 2010-03-11 | Phebra Pty Ltd | Analgesia by transmucosal administration |
EP2244783A2 (en) * | 2008-01-22 | 2010-11-03 | Vapogenix, Inc. | Volatile anesthetic compositions and methods of use |
EP2444425A1 (en) * | 2010-10-19 | 2012-04-25 | Wacker Chemie AG | 1:1, 2:1 or 3:1 complex consisting of a cyclodextrin or cyclodextrin derivative and a halogenated ether, production therof and use therof as soporific |
JP2012526133A (en) * | 2009-05-05 | 2012-10-25 | ベイポジェニックス インコーポレイテッド | Novel volatile anesthetic formulations and their use to reduce inflammation |
AU2015200210B2 (en) * | 2008-01-22 | 2016-08-11 | The Board Of Regents Of The University Of Texas System | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief |
WO2017011866A1 (en) | 2015-07-20 | 2017-01-26 | Medical Developments International Limited | Inhaler device for inhalable liquids |
WO2017011865A1 (en) | 2015-07-20 | 2017-01-26 | Medical Developments International Limited | Inhaler device for inhalable liquids |
WO2017011867A1 (en) | 2015-07-20 | 2017-01-26 | Medical Developments International Limited | Inhaler device for inhalable liquids |
EP2968214A4 (en) * | 2013-03-15 | 2017-04-12 | Vapogenix, Inc. | Novel analgesic compositions |
US11571526B2 (en) | 2016-09-06 | 2023-02-07 | Medical Developments International Limited | Inhaler device for inhalable liquids |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012177840A1 (en) * | 2011-06-24 | 2012-12-27 | Vapogenix, Inc. | Novel formulations and methods for treating dermatological disorders or diseases |
US20150321770A1 (en) * | 2014-03-09 | 2015-11-12 | Davy Zide Qian | New method to prevent or stop an airplane from being hijacked and to minimize the effect of damage by using remote and wireless real-time monitoring and inhalational general anesthetic gases controlled from the ground (level) |
CN104841025B (en) * | 2015-04-16 | 2017-10-24 | 河南科技大学第一附属医院 | It is a kind of to be used for the device of closed lumbar puncture and cerebrospinal fluid displacement |
CN110141508A (en) * | 2019-05-20 | 2019-08-20 | 崔文馨 | Sterile purification air physiological saline |
WO2023217384A1 (en) | 2022-05-13 | 2023-11-16 | Laboratorios Gebro Pharma, S.A. | Pharmaceutical composition for topical administration comprising a volatile anaesthetic |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4622219A (en) * | 1983-06-17 | 1986-11-11 | Haynes Duncan H | Method of inducing local anesthesia using microdroplets of a general anesthetic |
Family Cites Families (60)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE786675A (en) * | 1971-08-02 | 1973-01-25 | Airco Inc | SEPARATION OF ALKYL HALOGENOUS OXIDES BY AZEOTROPIC DISTILLATION. |
US4109651A (en) * | 1975-11-19 | 1978-08-29 | Steigerwald Allan M | Anesthetic gas exhaust system |
US4453951A (en) * | 1980-07-09 | 1984-06-12 | General Electric Co. | Process for the production of silicone carbide composite |
SE8008962L (en) * | 1980-12-18 | 1982-06-19 | Erik Allan Lindkvist | DEVICE FOR ANCESTIC MASK |
US4879062A (en) | 1981-10-20 | 1989-11-07 | Adamantech, Inc. | Preparation of a gel having gas transporting capability |
US4744989A (en) | 1984-02-08 | 1988-05-17 | E. R. Squibb & Sons, Inc. | Method of preparing liposomes and products produced thereby |
US5227165A (en) * | 1989-11-13 | 1993-07-13 | Nova Pharmaceutical Corporation | Liposphere delivery systems for local anesthetics |
US5677290A (en) * | 1990-05-10 | 1997-10-14 | Fukunaga; Atsuo F. | Therapeutic use of adenosine compounds as surgical anesthetics |
US5679650A (en) * | 1993-11-24 | 1997-10-21 | Fukunaga; Atsuo F. | Pharmaceutical compositions including mixtures of an adenosine compound and a catecholamine |
US5114715A (en) * | 1990-11-29 | 1992-05-19 | Sepracor Inc. | Methods of use and compositions of (s)-isoflurane and (s)-desflurane |
US5114714A (en) * | 1990-11-29 | 1992-05-19 | Sepracor, Inc. | Methods of use and compositions of (r)-isoflurane and (r)-desflurane |
DE4105972C2 (en) * | 1991-02-26 | 1999-06-02 | Draegerwerk Ag | Anesthetic dosing device |
GB9202238D0 (en) * | 1992-02-03 | 1992-03-18 | Wellcome Found | Compounds |
US5230778A (en) * | 1992-05-01 | 1993-07-27 | Gavlin Associates | Purification of isoflurane by extractive distillation |
US5916596A (en) | 1993-02-22 | 1999-06-29 | Vivorx Pharmaceuticals, Inc. | Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof |
GB9308306D0 (en) * | 1993-04-22 | 1993-06-09 | Univ Aberdeen | Analgesic composition |
HU221726B1 (en) * | 1993-07-30 | 2002-12-28 | Ardent Pharmaceuticals Inc. | Piperazine compounds, process for producing them and pharmaceutical compositions containing them |
GB9423542D0 (en) | 1994-11-22 | 1995-01-11 | Marples Brian A | Pharmaceutical compounds |
US5568910A (en) * | 1995-03-02 | 1996-10-29 | Delmarva Laboratories, Inc. | Anesthesia machine |
US6248788B1 (en) * | 1996-11-06 | 2001-06-19 | The Regents Of The University Of California | Therapeutic method with capsaicin and capasicin analogs |
US5874469A (en) | 1996-01-05 | 1999-02-23 | Alcon Laboratories, Inc. | Fluoroalkyl hydrocarbons for administering water insoluble or unstable drugs |
US5919826A (en) | 1996-10-24 | 1999-07-06 | Algos Pharmaceutical Corporation | Method of alleviating pain |
US20030212123A1 (en) * | 1997-05-05 | 2003-11-13 | Pfizer Inc. | COX-2 selective carprofen for treating pain and inflammation in dogs |
NZ500438A (en) | 1997-07-14 | 2001-11-30 | Adolor Corp | Compositions containing a compound having kappa opioid agonist activity for treatment of pruritis (itchiness) |
US20030185761A1 (en) * | 1997-10-01 | 2003-10-02 | Dugger Harry A. | Buccal, polar and non-polar spray or capsule containing drugs for treating pain |
US5976072A (en) * | 1998-01-29 | 1999-11-02 | Johns Hopkins University | Copa method for fiberoptic endotracheal intubation |
AR015744A1 (en) | 1998-04-01 | 2001-05-16 | Orion Corp | USE OF DEXMEDETOMIDINE FOR SEDATION IN INTENSIVE THERAPY |
US6830581B2 (en) * | 1999-02-09 | 2004-12-14 | Innercool Therspies, Inc. | Method and device for patient temperature control employing optimized rewarming |
US6869440B2 (en) * | 1999-02-09 | 2005-03-22 | Innercool Therapies, Inc. | Method and apparatus for patient temperature control employing administration of anti-shivering agents |
GB2350297A (en) | 1999-05-27 | 2000-11-29 | Abbott Lab | Injectable halogenated anesthetic formulation in emulsion form |
US6653354B2 (en) * | 1999-07-29 | 2003-11-25 | Protexeon Limited | NMDA antagonist comprising xenon |
US6706034B1 (en) * | 1999-12-30 | 2004-03-16 | Advanced Cardiovascular Systems, Inc. | Process for agent retention in biological tissues |
US6669954B2 (en) * | 2000-01-25 | 2003-12-30 | John R. Crison | Controlled release of drugs |
US20010036943A1 (en) * | 2000-04-07 | 2001-11-01 | Coe Jotham W. | Pharmaceutical composition for treatment of acute, chronic pain and/or neuropathic pain and migraines |
JP2003531863A (en) | 2000-05-02 | 2003-10-28 | アクション ファーマ アプス | Treatment of inflammation-related diseases in non-ischemic conditions |
US6770636B2 (en) * | 2000-08-18 | 2004-08-03 | Boehringer Ingelheim Pharma Kg | Phenyl-and phenylalkyl-substituted ethanolamines and ethylenediamines |
US20070021360A1 (en) | 2001-04-24 | 2007-01-25 | Nyce Jonathan W | Compositions, formulations and kit with anti-sense oligonucleotide and anti-inflammatory steroid and/or obiquinone for treatment of respiratory and lung disesase |
US7758890B2 (en) * | 2001-06-23 | 2010-07-20 | Lyotropic Therapeutics, Inc. | Treatment using dantrolene |
KR20040072720A (en) | 2002-01-10 | 2004-08-18 | 파마시아 앤드 업존 캄파니 | Use of cox-2 inhibitors in combination with antiviral agents for the treatment of papilloma virus infections |
US20030181426A1 (en) * | 2002-02-11 | 2003-09-25 | Eisenach James C. | Compositions and methods for treating pain using cyclooxygenase-1 inhibitors |
WO2003077939A1 (en) | 2002-03-19 | 2003-09-25 | Genset Sa | Treatment of metabolic disorders with a tnf receptor family member (fradj and/or cryptic) agonists or antagonists |
PT1534736E (en) | 2002-08-10 | 2010-09-07 | Univ Yale | Nogo receptor antagonists |
ATE546136T1 (en) * | 2002-10-11 | 2012-03-15 | Baxter Int | CARDIOPROTECTION AND NEUROPROTECTION PROCEDURES BY INTRAVENOUS ADMINISTRATION OF HALOGENATED VOLATILE ANESTHETIC AGENTS |
BRPI0409523A (en) | 2003-03-28 | 2006-04-18 | Acadia Pharm Inc | method for treating neuropathic pain, method of identifying a compound and pharmaceutical composition |
US20050008640A1 (en) | 2003-04-23 | 2005-01-13 | Wendy Waegell | Method of treating transplant rejection |
US20030173287A1 (en) * | 2003-05-06 | 2003-09-18 | Johnston Arthur W | Filter devices and methods of use |
AU2004241088B2 (en) | 2003-05-16 | 2010-08-05 | Acorda Therapeutics, Inc. | Compositions and methods for the treatment of CNS injuries |
CN1926147A (en) | 2003-08-07 | 2007-03-07 | 比奥根艾迪克Ma公司 | NOGO receptor antagonists |
EP1653934B1 (en) | 2003-08-15 | 2008-05-14 | AB Science | Use of c-kit inhibitors for treating type ii diabetes |
DE602004015142D1 (en) | 2003-08-29 | 2008-08-28 | Childrens Medical Center | ANTIANGIOGENIC PEPTIDES FOR TREATING OR PREVENTING ENDOMETRIOSIS |
US20050136444A1 (en) | 2003-09-25 | 2005-06-23 | Scully Audra L. | Treating neuropathic pain with neuropeptide FF receptor 2 agonists |
US8557861B2 (en) | 2004-09-28 | 2013-10-15 | Mast Therapeutics, Inc. | Low oil emulsion compositions for delivering taxoids and other insoluble drugs |
TW200633990A (en) | 2004-11-18 | 2006-10-01 | Takeda Pharmaceuticals Co | Amide compound |
US20060198891A1 (en) | 2004-11-29 | 2006-09-07 | Francois Ravenelle | Solid formulations of liquid biologically active agents |
WO2006064886A1 (en) | 2004-12-16 | 2006-06-22 | Anges Mg, Inc. | Agent for regulating bone formation |
WO2006088088A1 (en) | 2005-02-16 | 2006-08-24 | Astellas Pharma Inc. | Pain remedy containing rock inhibitor |
JP5569899B2 (en) | 2006-11-28 | 2014-08-13 | ウィスコンシン・アラムナイ・リサーチ・ファウンデーション | Fluoropolymer-based emulsion for intravenous delivery of volatile fluorinated anesthetics |
EP3581169A1 (en) | 2008-01-22 | 2019-12-18 | The Board Of Regents Of The University Of Texas System | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief |
US20110159078A1 (en) | 2008-01-22 | 2011-06-30 | Vapogenix, Inc | Volatile Anesthetic Compositions and Methods of Use |
WO2010129686A1 (en) | 2009-05-05 | 2010-11-11 | Vapogenix, Inc. | Novel formulations of volatile anesthetics and methods of use for reducing inflammation |
-
2007
- 2007-09-20 WO PCT/US2007/079097 patent/WO2008036858A2/en active Application Filing
- 2007-09-20 EP EP07842927.1A patent/EP2081562B1/en active Active
- 2007-09-20 AU AU2007299738A patent/AU2007299738B2/en not_active Ceased
- 2007-09-20 US US11/858,497 patent/US20080119820A1/en not_active Abandoned
- 2007-09-20 ES ES07842927.1T patent/ES2573253T3/en active Active
- 2007-09-20 JP JP2009529406A patent/JP2010504359A/en active Pending
- 2007-09-20 DK DK07842927.1T patent/DK2081562T3/en active
- 2007-09-20 CA CA2663857A patent/CA2663857C/en not_active Expired - Fee Related
- 2007-09-20 PL PL07842927T patent/PL2081562T3/en unknown
-
2011
- 2011-07-14 US US13/183,257 patent/US10357464B2/en active Active
-
2013
- 2013-10-09 JP JP2013211544A patent/JP5827658B2/en not_active Expired - Fee Related
-
2015
- 2015-10-16 JP JP2015204185A patent/JP6312146B2/en not_active Expired - Fee Related
-
2017
- 2017-09-07 JP JP2017171713A patent/JP2017218450A/en not_active Withdrawn
-
2019
- 2019-06-07 US US16/434,541 patent/US10799466B2/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4622219A (en) * | 1983-06-17 | 1986-11-11 | Haynes Duncan H | Method of inducing local anesthesia using microdroplets of a general anesthetic |
Non-Patent Citations (5)
Title |
---|
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 2000, ANDERSON R J ET AL: "Isoflurane blocks LTP of hippocampal CA1 neurons at concentrations that block recall during anesthesia" XP002477753 Database accession no. PREV200100096651 & SOCIETY FOR NEUROSCIENCE ABSTRACTS, vol. 26, no. 1-2, 2000, pages Abstract No.-405.7, 30TH ANNUAL MEETING OF THE SOCIETY OF NEUROSCIENCE; NEW ORLEANS, LA, USA; NOVEMBER 04-09, 2000 ISSN: 0190-5295 * |
ECKENHOFF M F ET AL: "Quantitative autoradiography of halothane binding in rat brain." THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS APR 1998, vol. 285, no. 1, April 1998 (1998-04), pages 371-376, XP002477752 ISSN: 0022-3565 * |
GARCIA-FERNANDEZ J ET AL: "Clinical actions of subarachnoid sevoflurane administration in vivo: a study in dogs." BRITISH JOURNAL OF ANAESTHESIA OCT 2005, vol. 95, no. 4, October 2005 (2005-10), pages 530-534, XP002477750 ISSN: 0007-0912 * |
MATUTE E ET AL: "Characterisation of sevoflurane effects on spinal somato-motor nociceptive and non-nociceptive transmission in neonatal rat spinal cord: An electrophysiological study in vitro." NEUROPHARMACOLOGY, vol. 44, no. 6, May 2003 (2003-05), pages 811-816, XP002477751 ISSN: 0028-3908 * |
TAKENOSHITA M ET AL: "Halothane suppresses inhibitory monosynaptic transmission" PROGRESS IN ANESTHETIC MECHANISM, XX, XX, vol. 3, no. 1994, 1995, pages 326-329, XP008089062 * |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9566251B2 (en) | 2008-01-22 | 2017-02-14 | Board Of Regents, The University Of Texas System | Volatile anesthetic compositions and methods of use |
EP2244783A2 (en) * | 2008-01-22 | 2010-11-03 | Vapogenix, Inc. | Volatile anesthetic compositions and methods of use |
WO2009094459A1 (en) * | 2008-01-22 | 2009-07-30 | The Board Of Regents Of The University Of Texas System | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief |
EP2244783A4 (en) * | 2008-01-22 | 2011-03-09 | Vapogenix Inc | Volatile anesthetic compositions and methods of use |
US10420720B2 (en) | 2008-01-22 | 2019-09-24 | The Board Of Regents Of The University Of Texas System | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief |
US9675544B2 (en) | 2008-01-22 | 2017-06-13 | The Board Of Regents Of The University Of Texas System | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief |
AU2009206390B2 (en) * | 2008-01-22 | 2014-10-30 | The Board Of Regents Of The University Of Texas System | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief |
AU2015200210B2 (en) * | 2008-01-22 | 2016-08-11 | The Board Of Regents Of The University Of Texas System | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief |
EP3581169A1 (en) * | 2008-01-22 | 2019-12-18 | The Board Of Regents Of The University Of Texas System | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief |
WO2010025505A1 (en) * | 2008-09-04 | 2010-03-11 | Phebra Pty Ltd | Analgesia by transmucosal administration |
JP2016047834A (en) * | 2009-05-05 | 2016-04-07 | ボード・オブ・リージエンツ,ザ・ユニバーシテイ・オブ・テキサス・システム | Novel formulations of volatile anesthetics and methods of use thereof for reducing inflammation |
JP2012526133A (en) * | 2009-05-05 | 2012-10-25 | ベイポジェニックス インコーポレイテッド | Novel volatile anesthetic formulations and their use to reduce inflammation |
US9744142B2 (en) | 2009-05-05 | 2017-08-29 | Board Of Regents, The University Of Texas Systems | Formulations of volatile anesthetics and methods of use for reducing inflammation |
EP3195896A1 (en) * | 2009-05-05 | 2017-07-26 | Board of Regents, The University of Texas System | Novel formulations of volatile anesthetics and methods of use for reducing inflammation |
EP2444425A1 (en) * | 2010-10-19 | 2012-04-25 | Wacker Chemie AG | 1:1, 2:1 or 3:1 complex consisting of a cyclodextrin or cyclodextrin derivative and a halogenated ether, production therof and use therof as soporific |
US10071065B2 (en) | 2013-03-15 | 2018-09-11 | Vapogenix, Inc. | Analgesic compositions |
US10507189B2 (en) | 2013-03-15 | 2019-12-17 | Vapogenix, Inc. | Analgesic compositions |
US9655867B2 (en) | 2013-03-15 | 2017-05-23 | Vapogenix, Inc. | Analgesic compositions |
US10688062B2 (en) | 2013-03-15 | 2020-06-23 | Vapogenix, Inc. | Analgesic compositions |
EP3854389A1 (en) * | 2013-03-15 | 2021-07-28 | Vapogenix, Inc. | Novel analgesic compositions |
US11304913B2 (en) | 2013-03-15 | 2022-04-19 | Vapogenix, Inc. | Analgesic compositions |
EP2968214A4 (en) * | 2013-03-15 | 2017-04-12 | Vapogenix, Inc. | Novel analgesic compositions |
WO2017011866A1 (en) | 2015-07-20 | 2017-01-26 | Medical Developments International Limited | Inhaler device for inhalable liquids |
US11672925B2 (en) | 2015-07-20 | 2023-06-13 | Medical Developments International Limited | Inhaler device for inhalable liquids |
WO2017011865A1 (en) | 2015-07-20 | 2017-01-26 | Medical Developments International Limited | Inhaler device for inhalable liquids |
WO2017011867A1 (en) | 2015-07-20 | 2017-01-26 | Medical Developments International Limited | Inhaler device for inhalable liquids |
US11571526B2 (en) | 2016-09-06 | 2023-02-07 | Medical Developments International Limited | Inhaler device for inhalable liquids |
Also Published As
Publication number | Publication date |
---|---|
CA2663857A1 (en) | 2008-03-27 |
US20190358173A1 (en) | 2019-11-28 |
US10799466B2 (en) | 2020-10-13 |
US20080119820A1 (en) | 2008-05-22 |
EP2081562A2 (en) | 2009-07-29 |
AU2007299738B2 (en) | 2013-03-28 |
US10357464B2 (en) | 2019-07-23 |
ES2573253T3 (en) | 2016-06-06 |
JP5827658B2 (en) | 2015-12-02 |
JP2017218450A (en) | 2017-12-14 |
WO2008036858A3 (en) | 2008-08-07 |
JP2010504359A (en) | 2010-02-12 |
PL2081562T3 (en) | 2017-05-31 |
JP2014074028A (en) | 2014-04-24 |
AU2007299738A1 (en) | 2008-03-27 |
US20110269843A1 (en) | 2011-11-03 |
JP6312146B2 (en) | 2018-04-18 |
CA2663857C (en) | 2017-10-31 |
EP2081562B1 (en) | 2016-02-24 |
JP2016041721A (en) | 2016-03-31 |
DK2081562T3 (en) | 2016-05-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10799466B2 (en) | Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief | |
US10420720B2 (en) | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief | |
US9566251B2 (en) | Volatile anesthetic compositions and methods of use | |
AU2019201703B2 (en) | Volatile anesthetic compositions and methods of use | |
CN101522180A (en) | Methods for delivering volatile anesthetics for regional anesthesia and/or pain relief | |
AU2015200210B2 (en) | Volatile anesthetic compositions comprising extractive solvents for regional anesthesia and/or pain relief |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 200780038190.4 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 07842927 Country of ref document: EP Kind code of ref document: A2 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007299738 Country of ref document: AU |
|
ENP | Entry into the national phase |
Ref document number: 2663857 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1757/DELNP/2009 Country of ref document: IN |
|
ENP | Entry into the national phase |
Ref document number: 2009529406 Country of ref document: JP Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2007299738 Country of ref document: AU Date of ref document: 20070920 Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007842927 Country of ref document: EP |