Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Application of lipid vehicles and use for drug delivery

a technology of lipid vehicles and lipids, applied in the direction of biocide, drug composition, antibody medical ingredients, etc., can solve the problems of increasing the risk of drug resistance, so as to reduce or prevent antibody-mediated resistance to antigenic therapeutic agents, the effect of easing irritation

Inactive Publication Date: 2007-01-04
UNIVERSITY OF PITTSBURGH
View PDF12 Cites 22 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention provides improved treatments for pain, pain-intensive disorders, muscle contraction disorders, and related conditions by providing compositions and methods for the intravesical administration of lipid vehicles. These vehicles can deliver lipophilic therapeutic agents with reduced irritation and antibody-mediated resistance. The vehicles can also be used for the intravesical delivery of antibiotics, anticancer treatments, and other drugs. The methods involve intravesical instillation of the lipid vehicles to treat various disorders affecting the genitourinary tract, gastrointestinal tract, pulmonary system, and other body systems. The invention provides a novel route for prolonged delivery of therapies and can be used to treat pain associated with these disorders."

Problems solved by technology

Neuropathic pain is typically experienced as burning, shooting, and unrelenting in its intensity, and can sometimes be more debilitating that the initial injury or the disease process which induced it.
Unfortunately, the few remedies that have been reported to alleviate this condition are effective in only a small percentage of patients.
However, since capsaicin application itself frequently causes burning pain and hyperalgesia apart from the neuropathic pain being treated, patient compliance has been poor and the drop out rates during clinical trials have exceeded fifty percent.
Dystonia disorders cause uncontrolled movement and prolonged muscle contraction, which can result in spasms, twisting body motions, tremor, or abnormal posture.
The lack of coordination between detrusor contraction and urethral relaxation causes urinary obstruction (i.e., partial or complete block of urination).
This creates a buildup of urinary pressure, and can lead to severe urinary tract damage and life-threatening consequences.
Hyperactive bladders can empty spontaneously and result in urinary incontinence (urge incontinence).
In addition, the uncoordinated contraction between the bladder and bladder outlet (vesical neck or external urinary sphincter) can result in vesicoureteral reflux with concomitant renal damage.
A major drawback of current botulinum toxin therapies is the development of antitoxin antibodies in patients.
Patients with botulinum toxin A resistance may benefit from injections with other serotypes, including botulinum toxin B, C, and F. However, differences in the duration of the effects of the other serotypes can be significant, and cause dramatic reductions in treatment efficacy (see M. F. Brin, 1997, Muscle Nerve.20(suppl 6):S146-S168).
The energetically unfavorable contact between the hydrophobic acyl chains and the aqueous solution surrounding the lipid molecules causes the polar headgroups and acyl chains to rearrange.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of lipid vehicles and use for drug delivery
  • Application of lipid vehicles and use for drug delivery
  • Application of lipid vehicles and use for drug delivery

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0147] A hyperactive bladder model in Sprague-Dawley rats was established by exposure to acetic acid, or protamine sulfate (PS) in potassium chloride (KCl) solution. This was followed by instillation of LP (liposomes) in saline (in the case of the former) or LP / KCl. CMG (continuous cystometrogram) changes were examined and results were compared with control (saline instillation), hyperactive bladder (acetic acid or PS / KCl) and treatment with LP.

[0148] Materials and Methods

[0149] Intravesical bladder pressure was recorded via a transurethral catheter in adult female Sprague-Dawley rats anesthetized with urethane (1.2 g / kg) administered by subcutaneous injection (sc). Some animals were pretreated with capsaicin (125 mg / kg, sc) four days prior to the experiments. Continuous cystometrograms (CMGs) were performed by slowly filling the bladder (0.04 ml / min) with solutions of various composition including saline, acetic acid (0.1%), potassium chloride (KCl, 500 mM), protamine sulfate (PS...

example 2

[0160] The results of the experiments described in Example 1 are presented herein below. In summary, ICl (intercontraction interval) was decreased after exposure to acetic acid (79.8% decrease) or PS / KCl (81% decrease). However, ICl was not changed by LP, PS, or KCl alone. The decrease in ICl was partly reversed after infusion of LP (172.8% increase) or LP / KCl (63% increase), but was not significantly changed after by saline or KCl administration. Pretreatment with capsaicin delayed the onset of the irritative effects of acetic acid by approximately 30 to 60 min, but did not change the magnitude after two hours of infusion.

[0161] CMGs in PS / KCl Infusion Group

[0162] As shown in Tables 1A-1C, infusion of PS (10 mg / ml) or KCl (500 mM) alone did not significantly change the CMGs. However infusion of PS / KCl provided an irritative effect after a delay of 30 to 40 min (FIGS. 2B, 2D). The ICl and compliance were significantly reduced by 79-83% (from 15.8±1.4 to 2.7±1.0 min or from 16.3±1....

example 3

[0177] An animal model for acute hyperactive bladder in rats was developed using intravesical infusion of protamine sulfate (PS), an agent used to break down urothelial barrier function, and physiological concentrations of potassium chloride (KCl).

[0178] Materials and Methods

[0179] Continuous CMGs were performed in urethane-anesthetized female rats. The bladder was filled (0.04 ml / min) with normal saline followed by intravesical infusion for a 60 minute period with a test solution comprising either KCl (100 or 500 mM) or PS (10 or 30 mg / ml). Following this, 10 mg / ml PS treated animals were infused intravesically with 100, 300, or 500 mM KCl. Some animals were pretreated with capsaicin (125 mg / ml, sc) four days before the experiments.

[0180] Animal Preparation

[0181] The study was performed on 40 female Sprague-Dawley rats weighing 250-300 gm. Animals were anesthetized with 1.2 gm / kg urethane injected subcutaneously. Body temperature was maintained in the physiological range using ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
concentrationsaaaaaaaaaa
diametersaaaaaaaaaa
diametersaaaaaaaaaa
Login to View More

Abstract

The present invention relates to compositions and methods for the administration of lipid-based vehicles to treat various disorders, including bladder inflammation, infection, dysfunction, and cancer. In various aspects, the compositions and methods of the invention are useful for prolonged delivery of drugs, e.g., antibiotics, pain treatments, and anticancer agents, to the bladder, genitourinary tract, gastrointestinal system, pulmonary system, and other organs or body systems. In particular, the present invention relates to liposome-based delivery of vanilloid compounds, such as resiniferatoxin, capsaicin, or tinyatoxin, and toxins, such as botulinum toxin, for the treatment of bladder conditions, including pain, inflammation, incontinence, and voiding dysfunction. Further related are methods of using these vehicles alone or in conjunction with antibodies, e.g., uroplakin antibodies, to improve duration of liposome attachment, and provide a long-term intravesical drug delivery platform. The present invention specifically relates to antibody-coated liposomes that are useful for targeting specific receptors for drug, peptide, polypeptide, or nucleic acid delivery. In one particular aspect, the present invention relates to liposomes coated with antibodies against nerve growth factor (NGF) receptor and containing NGF antisense nucleic acids, which are used as a treatment for neurogenic bladder dysfunction.

Description

RELATED APPLICATION [0001] This application is a continuation-in-part of U.S. application Ser. No. 60 / 311,868 filed Aug. 13, 2001, which is incorporated by reference herein in its entirety.FIELD OF THE INVENTION [0002] The present invention relates to compositions and methods for the Instillation of lipid vehicles (e.g., micelles, microemulsions, macroemulsions, and liposomes) to treat various disorders, including bladder inflammation and dysfunction. The vehicles of the present invention are useful for prolonged delivery of drugs such as antibiotics and anticancer agents to the bladder, genitourinary tract, gastrointestinal system, pulmonary system, and other organs or body systems. Specifically, the present invention relates to liposome-based delivery of resiniferatoxin, capsaicin, tinyatoxin, and other vanilloid compounds for the treatment of bladder pain, inflammation, incontinence, and voiding dysfunction. Also related is liposome-based delivery of toxins, such as botulinum tox...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/08A61K9/127A61K31/16A61K48/00A61K9/00A61K36/81A61P29/00A61P31/00A61P35/00
CPCA61K9/127A61K9/0034A61P29/00A61P31/00A61P35/00
Inventor CHANCELLOR, MICHAEL B.FRASER, MATTHEW O.CHUANG, YAO-CHIDE GROAT, WILLIAM C.HUANG, LEAFYOSHIMURA, NAOKI
Owner UNIVERSITY OF PITTSBURGH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com