Compositions and methods for inhibiting protein on surfaces

a technology of protein adsorption and composition, applied in the direction of detergent compounding agents, lens cleaning compositions, drug compositions, etc., can solve the problems of microbial contamination, support, and other devices or objects that can be adversely affected by protein adsorption, and achieve the effect of preventing microbial contamination

Inactive Publication Date: 2004-07-08
ALCON INC
View PDF16 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0026] Although not wishing to be bound by theory it is believed that the NIPAM polymers described herein have a range of inherent physical properties (e.g., low interfacial free energy, hydrophilic-hydrophobic properties, very low toxicity, dynamic surface mobility and steric stabilization) that enable these polymers to exhibit superior protein inhibiting characteristics.
[0035] The compositions of the present invention that are intended for use as CLC products will contain one or more ophthalmically acceptable antimicrobial agents in an amount effective to prevent microbial contamination of the compositions (referred to herein as "an amount effective to preserve"), or in an amount effective to disinfect contact lenses by substantially reducing the number of viable microorganisms present on the lenses (referred to herein as "an amount effective to disinfect").

Problems solved by technology

Sensors, chromatographic supports, immunoassays, membranes for separation, biomedical implants, prosthetic devices (e.g., contact lenses) and many other devices or objects can be adversely affected by protein adsorption.
Soft lenses typically contain a large amount of water, are quite porous, and bear ionic charges on the exposed surfaces of the lenses, while hard lenses are considerably less porous and generally do not bear ionic surface charges.
The ionic surfaces and porous nature of soft contact lenses can lead to significant problems when the lenses come into contact with the tear film due to the complex composition of the tear film, which is largely comprised of proteins, lipids, enzymes and various electrolytes.
The uptake of proteins from the tear fluid onto the lens is a common problem and depends on a number of factors, including the nature of the materials from which the lens is made.
This fouling can lead to dehydration of the lens and instability of the tear film, resulting in discomfort and lack of tolerance in the wearer.
Adsorption of proteins can also facilitate bacterial colonization and this can increase the risk of vision-threatening infections.
However, the use of these agents can lead to irritation, and in cases where rubbing and cleaning regimens are required, there is a possibility that the cleaning agents will not be used properly or will be used in a manner that damages the lenses.
These prior attempts to reduce protein binding have drawbacks.
Additionally, due to the positive charge character of these macromolecules, complex formation with anionic surfactants or other components of CLC products may lead to flocculation and phase separation in the formulation, which is a significant problem.

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
  • Compositions and methods for inhibiting protein on surfaces
  • Compositions and methods for inhibiting protein on surfaces
  • Compositions and methods for inhibiting protein on surfaces

Examples

Experimental program
Comparison scheme
Effect test

example 2

[0071] The prophylactic properties of NIPAM polymers were further evaluated using a 3-day cycling study. Two sets of lenses were prepared. One set was presoaked in the formulations shown in Table 2 before going into the lysozyme solution, whereas the other set was not. Both sets of lenses were then placed in the lysozyme solution for 8 hours (Day 1). At the end of the day all the lenses were rinsed and put in their respective formulations to soak overnight. The following day (Day 2), the lenses went back into the lysozyme for the day (8 hours). This was repeated to complete 3 cycles (3 Days). At the end of the experiment all the lenses were analyzed in accordance with the procedures described in Example 1. The results are presented in Table 3:

3TABLE 3 Uptake Amount of Lysozyme Removed Sample (ug / lens) sd (ug / lens) % Prophylaxis sd 9591-47A(PS) 124.1 9.1 261.9 67.8 0.8 9591-47B(PS) 151.5 3.9 234.5 60.8 0.6 9591-47C(PS) 386.0 6.1 -- -- --9591-47A 206.3 2.7 174.9 45.9 1.2 9591-47B 221....

example 3

[0074] The prophylaxis work was extended to formulations containing the antimicrobial agent AL-8496 with unmodified NIPAM (non-ionic) and modified NIPAM (end functionalized with COOH) polymers. The formulations evaluated are shown in Table 4, below:

4TABLE 4 Formulations for Microbiology Evaluation of PNIPAM Formulations Containing A Contact Lens Disinfecting Agent (AL-8496) Formulation Numbers 9591-44I Component 9591-44B 9591-44C 9591-44D 9591-44E 9591-44F (Control) P2991-NIPAM 0.087 0.21 P2426F2- 0.040 0.10 0.25 NIPAMCOOH AL-8496* 0.0004 0.0004 0.0004 0.0004 0.0004 0.0004 Tetronic .RTM. 1304 0.1 0.1 0.1 0.1 0.1 0.1 Sorbitol 0.4 0.4 0.4 0.4 0.4 0.4 Sodium borate 0.2 0.2 0.2 0.2 0.2 0.2 Sodium citrate 0.6 0.6 0.6 0.6 0.6 0.6 Propylene glycol 1.0 1.0 1.0 1.0 1.0 1.0 Disodium edetate 0.05 0.05 0.05 0.05 0.05 0.05 pH 7.8 7.8 7.8 7.8 7.8 7.8 % Prophylaxis 37.4 .+-. 0.2 54.1 .+-. 1.0 51.0 .+-. 0.5 57.3 .+-. 0.4 62.8 .+-. 1.2 0.6 .+-. 0.0 *As base

[0075] The procedures utilized were the sam...

example 4

[0077] The disinfection activity of the formulations shown in Table 4 above was also evaluated. The results are shown in Table 5 below.

5TABLE 5 Disinfection Properties of PNIPAM Formulations containing AL-8496 Time 9591- 9591- 9591-9591- 9591- 9591-Microorganism (hrs) 44B 44C 44D 44E 44F 44I Candida 6 2.8 3.0 3.0 3.4 3.2 3.0 albicans 24 3.9 4.5 6.0 6.0 5.3 6.0 Serratia 6 2.7 6.2 2.8 2.7 2.6 2.6 marcescens 24 5.5 6.2 5.5 6.2 5.5 4.9 Staphylococcus 6 5.5 4.5 5.5 4.4 4.3 4.9 aureus 24 6.2 5.0 6.2 6.2 6.2 5.2

[0078] The results demonstrate that the NIPAM polymers did not adversely affect the antimicrobial activity of the antimicrobial agent AL-8496.

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
molecular weightsaaaaaaaaaa
temperatureaaaaaaaaaa
volumeaaaaaaaaaa
Login to view more

Abstract

The use of NIPAM polymers to prevent or reduce the formation of protein deposits on the surfaces of medical devices is described. The invention is particularly directed to reduction of the adsorption of proteins on surfaces of contact lenses and other medical prosthetics.

Description

BACKGROUND OF INVENTION[0001] The present invention is directed to the reduction of protein deposition on surfaces. The invention provides compositions and methods for inhibiting the deposition of protein on the surfaces of medical devices, particularly biomedical and prosthetic devices. The invention is based on the discovery that certain polymers and related copolymers comprising the monomer n-isopropylacrylamide (NIPAM) significantly inhibit protein deposition on the surfaces of contact lenses.[0002] Proteins adsorb to almost all surfaces and the minimization or elimination of protein adsorption has been the subject of numerous studies, such as those reported by Lee, et al., in J. Biomed. Materials Res., vol. 23, pages 351-368 (1989). Sensors, chromatographic supports, immunoassays, membranes for separation, biomedical implants, prosthetic devices (e.g., contact lenses) and many other devices or objects can be adversely affected by protein adsorption. A method and / or means for tr...

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): A61L12/14C11D3/00C11D3/37
CPCA61L12/08A61L12/142A61L12/145Y10S514/839C11D3/3719C11D3/3773C11D3/0078Y10T428/31725A61L27/34A61L12/14A61L31/10
Inventor KETELSON, HOWARD ALLEN
Owner ALCON INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products