Phenol-Protein Solution Stability
(2022) KLGM15 20221Food Technology and Nutrition (M.Sc.)
- Abstract
- Phenol is a commonly used preservative in pharmaceutical protein solutions. It is compatible with most proteins but can cause aggregation and denaturation at higher concentrations or in more sensitive proteins. By titrating phenol in 12 different protein solutions with PS80 (Lysozyme, β -lactoglobulin, SOBI Lipase, GA-Z, Palifermin and Trastuzumab, all with and without NaCl) the phenol concentration at which the protein solution starts to be negatively affected has been determined. The impact of salt on the phenol sensitivity of the solutions has also been studied and DLS and SAXS tests have been made. The effects of PS80 has also been studied to determine if the protein or the surfactant is more sensitive to phenol.
- Popular Abstract
- Preserving the medicine of the future
Protein based medicines are an increasingly common part of our medical arsenal. In 2016 20 new protein based drugs were accepted by the EU while in 2017 it increased to 45 new drugs being accepted. While protein-based drugs allow for treatment of diseases that are difficult to handle otherwise they have to be produced as injectable solutions to avoid the stomach and intestines. As the body is adept at breaking down proteins the drug must be injected and can’t be given as a pill. The problem with solutions is that they have shorter shelf lives than pills. Therefore, preservatives that prevent bacteria from growing in the solution are necessary to produce a safe product.
Phenol is the most... (More) - Preserving the medicine of the future
Protein based medicines are an increasingly common part of our medical arsenal. In 2016 20 new protein based drugs were accepted by the EU while in 2017 it increased to 45 new drugs being accepted. While protein-based drugs allow for treatment of diseases that are difficult to handle otherwise they have to be produced as injectable solutions to avoid the stomach and intestines. As the body is adept at breaking down proteins the drug must be injected and can’t be given as a pill. The problem with solutions is that they have shorter shelf lives than pills. Therefore, preservatives that prevent bacteria from growing in the solution are necessary to produce a safe product.
Phenol is the most commonly used preservative for protein solutions because it is good at preventing bacterial growth even in low concentrations. Studying how phenol interacts with proteins can help formulate better protein solutions in the future and thereby improve or even save lives.
To study the effects of phenol a series of solutions were mixed to study what happens when the concentration of phenol increases. When the concentration of phenol gets too high the solution turns cloudy and quickly becomes useless. Therefore it is important to determine the correct amount of preservative needed to produce a solution that is both stable and safe to inject into a human.
These solutions consists of three major components: the protein, the surfactant and phenol. The protein is the active ingredient and the surfactant is a stabilizer that helps prevent the protein from clumping together and becoming useless. This surfactant can also be affected by phenol however and therefore studying how the three interact helps in designing future solutions.
Six proteins were studied, four of them (Trastuzumab, Palifermin, Sobi Lipase and GA-Z) were proteins that are used in medicine now and the other two (β-lactoglobulin, lysozyme) are proteins that are commonly tested in research. Two of these proteins, Trastuzumab and Palifermin, are used to treat some forms of cancer. These six proteins were tested with and without salt (Sodium Chloride) as that is commonly included in protein solutions and can affect how the proteins behave.
Some of the proteins can handle a higher concentration of phenol than others, with Sobi Lipase being several times more resistant to phenol than any other protein. This means that Sobi Lipase works quite well with phenol. Other proteins such as GA-Z and Palifermin however show no particular interaction with phenol and is not that stable when phenol is used as a preservative.
Within these six proteins there is a trend of salt creating a less stable solution but that is not the case for Trastuzumab which is several times larger and heavier than any of the other proteins. It is possible that the size of Trastuzumab helps reduce the impact of salt on the solution.
Through this study an increasing understanding of what produces a stable protein solution is possible which aids the field of medicine as a whole and can help cure rare diseases that are not otherwise treatable. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9098936
- author
- Sjölund, Johan LU
- supervisor
-
- Marie Wahlgren LU
- Johanna Hjalte LU
- organization
- course
- KLGM15 20221
- year
- 2022
- type
- H1 - Master's Degree (One Year)
- subject
- keywords
- Phenol, Protein, Proteins, Lysozyme, Betalactoglobulin, Trastuzumab, Lipase, GAZ, GA-Z, Palifermin, Titration, Probedrum, Pharmaceutical Technology
- language
- English
- id
- 9098936
- date added to LUP
- 2022-10-18 16:02:55
- date last changed
- 2022-10-18 16:02:55
@misc{9098936,
abstract = {{Phenol is a commonly used preservative in pharmaceutical protein solutions. It is compatible with most proteins but can cause aggregation and denaturation at higher concentrations or in more sensitive proteins. By titrating phenol in 12 different protein solutions with PS80 (Lysozyme, β -lactoglobulin, SOBI Lipase, GA-Z, Palifermin and Trastuzumab, all with and without NaCl) the phenol concentration at which the protein solution starts to be negatively affected has been determined. The impact of salt on the phenol sensitivity of the solutions has also been studied and DLS and SAXS tests have been made. The effects of PS80 has also been studied to determine if the protein or the surfactant is more sensitive to phenol.}},
author = {{Sjölund, Johan}},
language = {{eng}},
note = {{Student Paper}},
title = {{Phenol-Protein Solution Stability}},
year = {{2022}},
}