1. A method for treating or ameliorating symptoms in a subject with a disease associated with a particular cranial nerve, wherein the disease is a neurology-psychiatry-related affliction, an ear-nose-throat (ENT)-related affliction, a GU-related affliction, a gastrointestinal (GI)-related affliction, a cardiac-related affliction, a pulmonary-related affliction, or a metabolic-related affliction, the method comprising:
administering to an ear canal of a subject in need of such treatment an effective amount of a pharmaceutical composition comprising: (i) at least one analgesic comprising a pyrazolone derivative, and (ii) at least one anesthetic comprising Formula I:
wherein R1 comprises:
\u2003wherein R2 comprises H, CH3, Cl, or
wherein R3 comprises H or NH2; wherein R4 comprises H, NH2, CH3,
\u2003wherein R5 comprises H; and wherein R6 comprises H or CH3,
and wherein said pharmaceutical composition is administered to the ear canal of the subject in a concentration sufficient to physiologically alter the activity of the subject’s particular cranial nerve compared to the physiological activity of that particular cranial nerve in a subject not administered the pharmaceutical composition.
2. The method for claim 1, wherein R1 comprises
wherein R2 comprises H or CH3; wherein R3 comprises H;
wherein R4 comprises H, NH2,
wherein R5 comprises H; and wherein R6 comprises H or CH3.
3. The method for claim 1, wherein R1 comprises
wherein R2 comprises H or CH3; wherein R3 comprises H; wherein R4 comprises H, NH2, or
wherein R5 comprises H; and wherein R6 comprises H or CH3.
4. The method according to claim 1, wherein the particular cranial nerve is the trigeminal nerve, the facial nerve, the glossopharyngeal nerve, the accessory nerve, the hypoglossal nerve, the vagus nerve, or a combination thereof.
5. The method according to claim 1, wherein the neurology-psychiatry-related affliction is at least one selected from the group consisting of: chronic fatigue syndrome, fibromyalgia, epilepsy, Obsessive Compulsive Disorder, panic attack, Post-Traumatic Stress Disorder, Tourette’s Syndrome, Focal Dystonia, Tic Doloreaux, Bulimia, Anxiety, Depression, Restless Leg Syndrome, Dysautonomia, Familial Intentional Tremor, Migraine pain, Autism Spectrum Disorder, Anxiety Headache, sleeplessness, Reticular Activating System (RAS) dysregulation, Multiple Sclerosis, Peripheral Neuropathy, Apraxia, Neck and Shoulder Pain, Parkinson’s Disease, General Somatic Afferent Pain, General Visceral, Afferent Pain, opiate withdrawal, Dysarthria, ADHD, Nonspecific hand tremor, Stuttering, cerebral palsy, Raynaud’s Phenomenon, and excessive sweating.
6. The method of claim 5, wherein the General Somatic Afferent Pain comprises Neuromuscular Pain of the neck, back, arms, legs, or shoulders; Joint Pain; Sciatica pain; Arthritis pain; Shingles Pain; Reflex Sympathetic Dystrophy pain; or a combination thereof.
7. The method of claim 5, wherein a symptom of opiate withdrawal comprises Generalized Pain, Muscle Aches, Nausea, vomiting, Sweating, Diarrhea, or a combination thereof.
8. The method of claim 1, wherein the ear-nose-throat (ENT)-related affliction is at least one selected from the group consisting of: Palatal Myoclonus, Post Tonsillectomy Pain, Pharyngeal Pain, Laryngeal Pain, Neurogenic Cough, Globus Hystericus, Spasmodic Dysphonia, Snoring, Allergic Rhinitis, Chronic Sinusitis, Chronic Nasal Congestion, Allergic Conjunctivitis, Sneezing, Hiccups, Rhinitis, Tinnitus, Dysphagia, ear pain, neck pain, Dry Eye Syndrome, Trigeminal Neuralgia pain, and Temporomandibular Joint Pain.
9. The method according to claim 1, wherein GastroenterologyUrology (GU)-related affliction is at least one selected from the group consisting of: bladder spasm, dysmenorrhea, pelvic pain, Premature Labor, interstitial cystitis, Prostatitis, Eclampsia, pre-eclampsia, HELLP Syndrome, cystitis, Kidney Pain, enuresis, dysuria, dyspareunia, encopresis, heavy flow menstruation, frequent urination, Prolonged Vaginal Bleeding, and decreased renal blood flow.
10. The method of claim 1, wherein the gastrointestinal (GI)-related affliction is at least one selected from the group consisting of: irritable bowel syndrome (IBS), ulcerative colitis, acid reflux, Gastritis, Gastroenteritis, Hyperemesis Gravidarum, Pediatric Colic, Hepato-Renal Syndrome, Appetite Suppression, Gall Bladder Pain, Chronic constipation, Chronic diarrhea, and Pancreatitis.
11. The method of claim 1, wherein the cardiac-related affliction is at least one selected from the group consisting of: Paroxysmal (Lone) (Vagal) Atrial Fibrillation, Orthostatic (Neurogenic) Hypotension, Reflex Asystolic Syncope, Postural Orthostatic Tachycardia Syndrome (POTS), Vasovagal Reflex, cardiac surgery derived cough, heart block, Atrial Contractions, Tachycardia, and Congestive Heart Failure.
12. The method of claim 1, wherein the pulmonary-related affliction is at least one selected from the group consisting of: asthma, chronic obstructive pulmonary disease (COPD), bronchitis, cystic fibrosis, and Bronchospasm.
13. The method of claim 1, wherein the metabolic-related affliction is at least one selected from the group consisting of: hypertension, diabetes, septic shock, neurogenic shock, hyperglycemia, and hypercholesteremia.
14. The method of claim 1, wherein the pyrazolone derivative is selected from the group consisting of ampyrone, dipyrone, antipyrine, aminopyrine, and propyphenazone.
15. The method according to claim 1, wherein the analgesic is antipyrine.
16. The method according to claim 1, wherein the anesthetic comprises benzocaine, chloroprocaine, cocaine, cyclomethycaine, dimethocaine, larocaine, piperocaine, propoxycaine, procaine, novocaine, proparacaine, tetracaine, amethocaine, articaine, bupivacaine, cinchocaine, dibucaine, etidocaine, levobupivacaine, lidocaine, lignocaine, mepivacaine, prilocaine, ropivacaine, farmocaine, trimecaine, a combination of the anesthetics listed herein, or pharmaceutically acceptable derivatives thereof.
17. The method according to claim 1, wherein the anesthetic is benzocaine.
18. The method according to claim 1, wherein the anesthetic is lidocaine.
19. The method according to claim 1, wherein the anesthetic is tetracaine.
20. The method according to claim 1, wherein the anesthetic comprises lidocaine and tetracaine.
21. The method according to claim 1, wherein the subject does not have an ear infection.
22. The method according to claim 1, wherein the pharmaceutical composition further comprises one or more of an antibiotic, a vasoconstrictor, glycerin, epinephrine, or acetic acid.
23. The method according to claim 1, wherein the pharmaceutical composition is administered in a solution.
24. The method according to claim 1, wherein the pharmaceutical composition is administered in a foam.
25. The method according to claim 1, wherein the analgesic is present in the pharmaceutical composition in a concentration of from about 50 to about 60 mg per mL and the anesthetic is present in the pharmaceutical composition in a concentration of from about 2 to about 20 mg per mL.
26. The method according to claim 1, wherein the analgesic is present in the pharmaceutical composition in a concentration of from about 50 to about 55 mg per mL and the anesthetic is present in the pharmaceutical composition in a concentration of from about 2 to about 15 mg per mL.
27. An otic pharmaceutical composition, the composition comprising (i) at least one analgesic comprising a pyrazolone derivative, and (ii) at least one anesthetic comprising Formula I:
wherein R1 comprises:
wherein R2 comprises H, CH3, Cl, or
wherein R3 comprises H or NH2; wherein R4 comprises H, NH2, CH3,
wherein R5 comprises H; and wherein R6 comprises H or CH3, and
wherein the analgesic is present in the pharmaceutical composition in a concentration of from about 50 to about 60 mg per mL, and wherein the anesthetic is present in the pharmaceutical composition in a concentration of from about 2 to about 20 mg per mL.
28. The composition of claim 27, wherein R1 comprises,
wherein R2 comprises H or CH3; wherein R3 comprises H; wherein R4 comprises H, NH2, or
wherein R5 comprises H; and wherein R6 comprises H or CH3.
29. The composition of claim 27 further comprising an antibiotic, a vasoconstrictor, glycerin, epinephrine, acetic acid, or a combination thereof.
30. The composition of claim 27, wherein the analgesic comprises antipyrine.
31. The composition of claim 27, wherein the anesthetic comprises lidocaine, tetracaine, benzocaine, or a combination thereof.
32. The composition of claim 27, wherein the anesthetic comprises lidocaine, tetracaine, or a combination thereof.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A phase shift circuit comprising:
an on signal generator for generating an on signal having a rising edge shifted by a predetermined phase based on a pulse width modulation (PWM) signal;
an off signal generator for generating an off signal based on the PWM signal and the on signal; and
a channel signal generator for generating a channel signal that is enabled in response to the rising edge of the on signal and disabled in response to a rising edge of the off signal.
2. The phase shift circuit of claim 1, wherein the on signal generator comprises:
a first ramp signal generator for generating a ramp signal that linearly increases in each period of the PWM signal in response to the PWM signal;
a peak signal generator for generating a peak signal that maintains a peak value of the ramp signal based on the ramp signal;
a voltage divider for providing a divided peak signal by dividing the peak signal by a predetermined ratio; and
a first comparator for generating the on signal by comparing the divided peak signal with the ramp signal.
3. The phase shift circuit of claim 2, wherein the first ramp signal generator comprises:
a first ramp signal unit for generating a first ramp signal that linearly increases during an odd-numbered period of the PWM signal in response to the PWM signal;
a second ramp signal unit for generating a second ramp signal that linearly increases during an even-numbered period of the PWM signal in response to the PWM signal; and
a summer for providing the ramp signal by summing up the first ramp signal and the second ramp signal.
4. The phase shift circuit of claim 3, wherein the first ramp signal unit comprises:
a first flip flop for providing a transformed PWM signal that is toggled in each period of the PWM signal; and
a first capacitor, to which electric charges are charged based on the transformed PWM signal,
wherein the first ramp signal unit provides a voltage between both terminals of the first capacitor as the first ramp signal.
5. The phase shift circuit of claim 4, wherein the first ramp signal unit further comprises a discharge transistor that discharges electric charges charged to the first capacitor in response to a complementary transformed PWM signal, which is an inverse signal of the transformed PWM signal.
6. The phase shift circuit of claim 4, wherein the first ramp signal unit further comprises:
a first amplifier comprising a non inverting terminal, to which the transformed PWM signal is input, and an inverting terminal connected to a first node; and
a first resistor connected between the first node and a ground voltage, wherein a current that corresponds to a current flowing in the first resistor is charged to the first capacitor.
7. The phase shift circuit of claim 6, wherein the peak signal generator comprises:
a third capacitor, to which electric charges are charged based on the transformed PWM signal; and
a first transistor connected to the third capacitor in series that allows electric charges to be charged in the third capacitor in response to a peak enable signal, which samples an initial period of the transformed PWM signal,
wherein the peak signal generator provides a voltage of both terminals of the third capacitor as the peak signal.
8. The phase shift circuit of claim 7, wherein the third capacitor of the peak signal generator is charged by a current that corresponds to the current flowing in the first resistor.
9. The phase shift circuit of claim 1, wherein the off signal generator comprises:
a duty signal generator for generating a duty peak signal having a value that is in proportion to a duty ratio of the PWM signal;
a second ramp signal generator for generating an on ramp signal based on the on signal; and
a second comparator for generating the off signal by comparing the on ramp signal with the duty peak signal.
10. The phase shift circuit of claim 9, wherein the duty signal generator comprises:
a duty ramp signal generator for generating a duty ramp signal that linearly increases while the PWM signal is in a logic \u2018high\u2019 state; and
a duty peak signal generator for generating the duty peak signal that maintains a peak value of the duty ramp signal based on the duty ramp signal.
11. The phase shift circuit of claim 1, wherein the channel signal generator comprises a channel capacitor that is charged in response to the on signal and discharged in response to the off signal, and provides a voltage of both terminals of the channel capacitor as the channel signal.
12. A phase shift circuit comprising:
an on signal generator for generating an on signal having a rising edge shifted by a selected phase based on a pulse width modulation (PWM) signal;
an off signal generator for generating an off signal based on the PWM signal and the on signal; and
a channel signal generator for generating a channel signal that is enabled in response to the rising edge of the on signal and disabled in response to a rising edge of the off signal.
13. The phase shift circuit of claim 12, wherein the on signal generator comprises:
a ramp signal generator for generating a ramp signal that linearly increases during a period of the PWM signal in response to the PWM signal;
a peak signal generator for generating a peak signal that maintains a peak value of the ramp signal based on the ramp signal;
a voltage divider for providing at least one divided peak signal by dividing the peak signal based on a phase selection signal for selecting the phase; and
a comparator for generating the at least one on signal by comparing the at least one divided peak signal with the ramp signal.
14. The phase shift circuit of claim 13, wherein the on signal generator further comprises a controller that generates the phase selection signal.
15. The phase shift circuit of claim 13, wherein the voltage divider comprises:
a plurality of division resistors connected in series between a node, to which the peak signal is applied, and a ground voltage; and
at least one switch comprising one end connected to at least one node between the plurality of division resistors and the other end for providing the divided peak signal, when the at least one switch is turned on in response to the phase selection signal.
16. The phase shift circuit of claim 15, wherein a ratio of the divided peak signal to the peak signal is in proportion to the selected phase.
17. A dimming circuit comprising:
a phase shift circuit for providing a plurality of channel signals having phases different from each other based on a pulse width modulation (PWM) signal;
a gate control integrated circuit (IC) electrically connected to the phase shift circuit, for generating a gate control signal;
a driver for providing an input voltage in response to the gate control signal; and
a plurality of light emitting diode (LED) strings driven based on the input voltage and the plurality of channel signals.
18. The dimming circuit of claim 17, wherein the driver comprises:
a gate transistor for grounding the input voltage in response to the gate control signal; and
a capacitor for planarizing the input voltage and providing the planarized input voltage to one end of the plurality of LED strings.
19. The dimming circuit of claim 17, wherein the phase shift circuit comprises:
an on signal generator for generating a plurality of on signals having rising edges shifted by the phases that are different from each other based on the PWM signal;
an off signal generator for generating a plurality of off signals having rising edges after pulse duration of the PWM signal is elapsed from a point of time when the corresponding on signals have the rising edges, based on the PWM signal and the corresponding on signals; and
a channel signal generator for generating a plurality of channel signals that are each enabled in response to the rising edges of the correspondging on signals and disabled in response to the rising edges of the correspondging off signals.
20. The dimming circuit of claim 19, wherein each of the plurality of LED strings comprises a switch that is turned on in response to the channel signal.