A method for producing and purifying rna, comprising at least one step of tangential flow filtration
US-2018298372-A1 · Oct 18, 2018 · US
US11529588B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-11529588-B2 |
| Application number | US-201816627370-A |
| Country | US |
| Kind code | B2 |
| Filing date | Jun 29, 2018 |
| Priority date | Jun 30, 2017 |
| Publication date | Dec 20, 2022 |
| Grant date | Dec 20, 2022 |
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A cleaning solution for accelerated cleaning of a membrane having an enzyme and an agent having a pH that is compatible with the enzyme. The cleaning solution may additionally include one or both of a binding agent and a surfactant. Once the cleaning solution has been included in a solution that is used to contact the membrane for a defined period of time, one or both of a binding agent and a reducing agent may be added to the solution that has contacted the membrane. Optionally, one or both of increasing a pH of the solution and increasing a temperature of the solution may be used to reduce an activity of the enzyme.
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That which is claimed: 1. A method of cleaning a membrane, the method comprising: pre-rinsing the membrane; cleaning the membrane using a solution comprising an enzyme and a buffer having a pH compatible with the enzyme, the solution having a temperature compatible with the membrane; preventing any divalent ions in the solution from precipitation; reducing an activity of the enzyme by adding a first binding agent capable of deactivating the enzyme to the solution, wherein the reducing activity of the enzyme is performed up to about 40 minutes, wherein the first binding agent is chosen from: ethylenediaminetetraacetic acid (EDTA) or any salt thereof, (hydroxyethyl) ethylenediaminetriacetic acid (HEDTA) or any salt thereof, potassium tripolyphosphate (KTPP), a phosphonic acid or any salt thereof, nitrilotriacetic acid (NTA) or any salt thereof, diethylene triamine pentaacetic acid (DTPA) or any salt thereof, glutamic acid diacetic acid (GLDA) or any salt thereof, methylglycinediacetic acid (MGDA) or any salt thereof, iminodisuccinc acid (IDS) or any salt thereof, aminocarboxylic acids or any salt thereof, hydroxyethane diphosphonic acid (HEDP) or any salt thereof, amino tris(methylenephosphonic acid) (ATMP) or any salt thereof, 2-phosphonobutane-1,2,4-tricarboxylic acid (PBTC) or any salt thereof, ethylenediamine tetra(methylene phosphonic acid) (EDTMP) or any salt thereof, diethylenetriamine penta(methylene phosphonic acid) (DTPMP) or any salt thereof, polyacrylate, acrylic acid-maleic acid copolymer or any salt thereof, or any combination thereof, and wherein the method is without rinsing the solution from the membrane between the time the solution is contacted with the membrane to the time used for reducing the activity of the enzyme; and post-rinsing the membrane for removal of the solution. 2. The method of claim 1 , wherein the solution additionally comprises a second binding agent capable of forming complex with the divalent ions in the solution. 3. The method of claim 2 , wherein the second binding agent capable of forming complex with the divalent ions comprises at least one of ethylenediaminetetraacetic acid (EDTA) and any salt thereof, (hydroxyethyl)ethylenediaminetriacetic acid (HEDTA) and any salt thereof, potassium tripolyphosphate (KTPP), a phosphonic acid and any salt thereof, nitrilotriacetic acid (NTA) and any salt thereof, diethylene triamine pentaacetic acid (DTPA) and any salt thereof, gluconic acid (GA) and any salt thereof, glutamic acid diacetic acid (GLDA) and any salt thereof, methylglycinediacetic acid (MGDA) and any salt thereof, iminodisuccinc acid (IDS) and any salt thereof, aminocarboxylic acids and any salt thereof, hydroxyethane diphosphonic acid (HEDP) and any salt thereof, aminotris(methylenephosphonic acid) (ATMP) and any salt thereof, 2-phosphonobutane-1,2,4-tricarboxylic acid (PBTC) and any salt thereof, ethylenediamine tetra(methylene phosphonic acid) (EDTMP) and any salt thereof, diethylenetriamine penta(methylene phosphonic acid) (DTPMP) and any salt thereof, a polyacrylate, an acrylic acid-maleic acid copolymer and any salt thereof, and sodium gluconate (Na-gluconate). 4. The method of claim 3 , wherein a concentration of the second binding agent capable of forming complex with the divalent ions is from about 0.001 wt % to about 1 wt % based on the overall weight of the solution. 5. The method of claim 3 , wherein the polyacrylate comprises a partially neutralized polyacrylic acid having a molecular weight in the range of about 2.5 k to about 5 k. 6. The method of claim 1 , wherein the solution additionally comprises a surfactant. 7. The method of claim 6 , wherein the surfactant comprises at least one of an anionic, a non-ionic and an amphoteric surfactant. 8. The method of claim 1 , wherein the method fulfills at least one of the following: (i) a concentration of the first binding agent capable of deactivating the enzyme is from about 0.005 wt % to about 1 wt % based on the overall weight of the solution; (ii) a ratio by weight of the first binding agent capable of deactivating the enzyme to the enzyme is at least about 0.2 g binding agent to gram of enzyme; (iii) a ratio by weight of the first binding agent capable of deactivating the enzyme is from about 0.2 to about 200 g binding agent per gram of enzyme; (iv) a ratio by weight of the first binding agent capable of deactivating the enzyme is from about 0.2 to about 80 g binding agent per gram of enzyme. 9. The method of claim 1 , wherein the method further comprises reducing activity of the enzyme by adding a reducing agent to the solution. 10. The method of claim 9 , wherein the reducing agent comprises sodium dithionite. 11. The method of claim 10 , wherein the method fulfills at least one of the following: (i) the sodium dithionite concentration is at least about 0.2 wt %; (ii) the sodium dithionite concentration is from about 0.25 wt % to about 10 wt %; (iii) the sodium dithionite concentration is from about 0.25 wt % to about 2.5 wt %. 12. The method of claim 1 , wherein the method further comprises reducing activity of the enzyme by increasing the pH of the solution, or increasing the temperature of the solution, or both. 13. The method of claim 12 , wherein the pH is increased from about 11 to about 13. 14. The method of claim 12 , wherein the temperature is increased from about 50° C. to about 85° C. 15. The method of claim 12 , wherein the pH is increased from about 12.0 to about 13.0 and the temperature is increased from about 50° C. to about 60° C. 16. The method of claim 12 , wherein the pH is increased from about 11.0 to about 12.0 and the temperature is increased from about 60° C. to about 85° C. 17. The method of claim 1 , wherein the membrane has been used for the treatment of proteins. 18. The method of claim 17 , wherein the membrane has been used for the treatment of acid whey, sweet whey, skim milk, or combinations thereof. 19. The method of claim 1 , wherein the method fulfills at least one of the following: (a) pre-rinsing the membrane is performed using a pre-rinse solution comprising water for a period of from about 2 minutes to about 30 minutes; (b) cleaning the membrane is performed for a period of from about 2 minutes to about 45 minutes; (c) post-rinsing the membrane is performed using a post-rinse solution comprising water for a period of from about 2 minutes to about 30 minutes. 20. The method of claim 1 , wherein the enzyme is chosen from proteases, amylases, lipases, or any mixture thereof. 21. The method of claim 1 , wherein the membrane has been used for the treatment of proteins, fats, or any combination thereof.
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