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Method of treating neutrophil-related diseases with topical anesthetics

a topical anesthetic and neutrophil technology, applied in the field of topical anesthetics for treating neutrophil-related diseases, can solve the problems of emphysematous changes, glucocorticoids have no effect on the long-term decline of pulmonary function, and difficult definition of morphological description

Inactive Publication Date: 2006-05-11
MAYO FOUND FOR MEDICAL EDUCATION & RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

COPD is a complex condition with an imprecise definition, which makes a definitive morphological description difficult.
It is believed that emphysematous changes are also the result of neutrophil-induced parenchymal damage.
Furthermore, studies have shown that glucocorticoids have no effect on the long-term decline of pulmonary function in patients with COPD.
It has been recently shown that some patients with severe asthma have only neutrophils in their sputum, and these patients do not respond to glucocorticoids.
At this time, there is no effective anti-inflammatory therapy for these patients.
Other than smoking cessation, there is no established treatment for the neutrophilic inflammation in chronic bronchitis and COPD, nor the progressive pulmonary function decline in patients with COPD.
Unfortunately, smoking cessation is not a realistic therapeutic remedy in the vast number of patients effected.
This means that over three fourths of these patients (about 25% of the US adult population) continue to smoke and develop neutrophilic airway inflammation, and risk sustaining variable degrees of progressive airway and parenchymal damage.
Furthermore, smoking cessation may take years to accomplish or not be possible at all for most patients who smoke.
In cystic fibrosis, the normal protective defenses against proteases are intact, but the inflammation on the airway epithelial surface is so intense that these defenses against neutrophil elastase are overwhelmed and rendered ineffective.

Method used

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  • Method of treating neutrophil-related diseases with topical anesthetics
  • Method of treating neutrophil-related diseases with topical anesthetics
  • Method of treating neutrophil-related diseases with topical anesthetics

Examples

Experimental program
Comparison scheme
Effect test

example 1

Inhibition of Neutrophil Superoxide Production by Lidocaine

[0043] Lidocaine has an inhibitory effect on neutrophil superoxide production. Neutrophils were purified from heparinized venous blood of normal volunteers by sedimentation through a cushion of 1.085 gm / ml Percoll made in PIPES buffer, pH 7.4, supplemented with 50 mM NaCl, 5 mM KCl, 25 mM NaOH, and 5.4 mM glucose) and centrifuged at 2,000 rmp in a Beckman CS-6KR centrifuge for 30 minutes with no brake. Plasma, mononuclear cells, and Percoll layers were removed and the erythrocytes were lysed by osmotic shock. The remaining pellet, which was ˜90% neutrophils, was used in the experiment.

[0044] The superoxide production was measured using cytochrome c reduction in a plate assay at a concentration of 50,000 neutrophils / well and was done in duplicate. There was no superoxide release in the absence of stimulus; TNF-alpha induced superoxide release was almost totally inhibited by 3 mM lidocaine, but PMA induced superoxide product...

example 2

Case Report of Patient with Bronchitis Treated with Lidocaine Inhalation

[0045] The patient was a 36-year-old female first seen in 1996 with a six month history of harsh cough affecting her both during the night and the day. Copious (about 50 ml per day), thick, yellow to white sputum was produced. She was often awakened at night with chest heaviness and dyspnea. Albuterol treatment reduced the cough and minimally alleviated the chest tightness. The patient was treated with prednisone and antibiotics on two occasions and this treatment improved her symptoms, but did not eliminate the sputum production. The patient worked as a scrub nurse in an operating room, but she did not note any worsening of her symptoms while at work or at home. When initially evaluated, the patient was receiving prednisone, 30 mg every other day, Salmeterol twice daily and Asthmacort four inhalations four times a day. Two sputum examinations revealed a striking infiltration with neutrophilic leukocytes.

[0046...

example 3

Treatment of Airway Neutrophilia in Chronic Bronchitis and COPD

[0050] In preliminary studies, it was discovered that lidocaine has potent anti-inflammatory properties with the ability, in vitro, to inhibit cytokine-stimulated eosinophilopoesis and prolongation of survival, activation, respiratory burst, and degranulation of eosinophils. Okada. S. et al., J. Immunol. 160:4010-4017 (1998). Subsequent in vivo studies have shown that lidocaine inhalation reduces or eliminates systemic glucocorticoids in most adult (Hunt, L. W. et al., Mayo Clinic Proc. 71:361-368 (1996)) and pediatric (Decco, M. L. et al., Ann. Allergy Asthma Immunol. 82:29-32 (1999)) patients with steroid-dependent asthma, and is able to replace topical glucocorticoids in patients with mild to moderate asthma. In the latter study, nebulized lidocaine also prevented the rise in peripheral blood eosinophils when topical glucocorticoids were withdrawn.

[0051] In vitro studies show that lidocaine inhibits depolarization o...

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Abstract

A therapeutic method is provided to treat neutrophil-associated pulmonary diseases, such as chronic obstructive pulmonary disease, by locally administering to a mammal in need of such treatment, an effective amount of a topical anesthetic, such as lidocaine, or a pharmaceutically acceptable salt thereof.

Description

RELATED APPLICATION [0001] This application is a Continuation of U.S. patent application Ser. No. 10 / 683,808 filed on Oct. 10, 2003 which is a divisional under 37 C.F.R. 1.53(b) of U.S. patent application Ser. No. 10 / 326,224 filed Dec. 20, 2002, which is a continuation under 35 U.S.C. 111(a) of International Application No. PCT / US01 / 19977 filed Jun. 22, 2001 and published in English as WO 02 / 00218 A2 on Jan. 3, 2002, which claimed priority from U.S. Provisional Application Ser. No. 60 / 214,031 filed Jun. 23, 2000, which applications and publication are incorporated herein by reference.BACKGROUND OF THE INVENTION [0002] There are several neutrophil-associated pulmonary diseases, including chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), pulmonary emphysema, α-1 anti-trypsin deficiency, cystic fibrosis, idiopathic pulmonary fibrosis, and adult respiratory distress syndrome. [0003] In chronic bronchitis there is cough and mucous hypersecretion with enlargement of t...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/24A61K9/72A61K31/167A61K31/245A61K31/445A61K31/4453A61K31/47A61K45/00A61P11/00
CPCA61K31/167A61K31/24A61K31/245A61K31/445A61K31/4453A61K31/47Y10S514/826Y10S514/87Y10S514/851A61P11/00
Inventor GLEICH, GERALD J.HUNT, LOREN W. JR.
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES