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Post by peppy on Jul 5, 2015 14:51:31 GMT -5
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Post by peppy on Jul 5, 2015 14:53:25 GMT -5
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Post by peppy on Jul 5, 2015 14:55:09 GMT -5
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Post by peppy on Jul 5, 2015 15:41:45 GMT -5
Insulin glargine is a human
insulin analogue designed to have a low solubility
at neutral pH. At pH 4, insulin glargine
injection solution is completely soluble.
HUMALOG U-200 contains insulin lispro 200 units, 16 mg glycerin, 5 mg tromethamine, 3.15 mg Metacresol, zinc oxide
content adjusted to provide 0.046 mg zinc ion, trace amounts of phenol, and Water for Injection. Insulin lispro has a pH of
7.0 to 7.8. The pH is adjusted by addition of aqueous solutions of hydrochloric acid 10% and/or sodium hydroxide 10%. Attachment DeletedAttachment DeletedAttachment Deleted
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Post by peppy on Jul 5, 2015 16:15:19 GMT -5
Insulin, which is both a hormone and a protein, is a balled-up string of chemicals called amino acids. Human insulin's sequence of 51 amino acids differs from that of pork insulin by a single amino acid and by three amino acids from beef insulin. In 1978, researchers at a burgeoning biotechnology company called Genentech announced that they had introduced a human gene for insulin into a safe strain of E. coli bacteria, which then produced the protein. Genentech partnered with Lilly, which brought engineered human insulin to the market in 1982 under the brand name Humulin, the first recombinant DNA drug product in the world. Biotechnology allowed people with diabetes to take insulin that is virtually identical to the body's version. But that was just the beginning for insulin medications. Having the ability to tweak the insulin gene, scientists started to develop new-to-nature forms of insulin—called insulin analogs—such as insulin lispro (Humalog) and insulin glargine (Lantus). Analogs have become increasingly popular among prescribers and patients. Engineers build desirable properties into analogs by tweaking their amino acid sequences in ways that force the body to process them faster or slower than plain human insulin. These new attributes give people with diabetes more options for controlling blood glucose. Lilly agreed to take Diabetes Forecast on a tour of parts of its Indianapolis insulin production complex. Covering 1.38 million square feet, or 18 soccer fields, the Lilly facilities in Indianapolis are constantly generating Humulin and the insulin analog Humalog. At Lilly, insulin-making E. coli is grown in 50,000-liter tanks called fermentors. There are more than 5,000 tanks on site.According to Lilly, a batch of insulin from one fermentor could produce a year's supply of insulin for thousands of people. "Our facilities are designed to produce insulin crystals in multiple metric-ton quantities," Walsh says.
The E. coli have humble beginnings. Small tubes of the bacteria have been stored in a freezer at minus 70 degrees Celsius (minus 94 degrees Fahrenheit) for decades. Lilly produced a granddaddy batch of E. coli, now referred to as the "master cell bank," sometime in the 1980s. It has gone on to seed every batch of Humulin to this day. Whenever Lilly wants a fresh stash of Humulin, workers go to the freezer, pull out a tube from the master cell bank, thaw it out, and stimulate the bacteria to grow. Starting with a mere half gram of bacteria, the microorganisms begin to replicate prodigiously, doubling their numbers every 20 minutes or so. Once a tube gets too crowded, the bacteria are moved into larger and larger domiciles, from flask to bigger flask and from tank to bigger tank. All the microorganisms need to flourish is a source of water, sugar, salt, and nitrogen, which their handlers generously supply. In addition, the bacterial broth contains an additive that helps keep any contaminating microorganisms at bay, says Walsh. Typically, the E. coli are engineered to be resistant to a particular antibiotic, such as ampicillin, so that adding ampicillin to a broth will kill off everything but the prized protein producers. After several days of reproduction, the bacteria are now ready to start their real job—making insulin.
Until this point, the bacteria have been kept from making insulin by a repressor protein that sits near the insulin gene. To jump-start insulin production, the researchers free up the insulin gene by adding a chemical called an inducer to the giant vat of teeming bacteria. The critters promptly begin to churn out insulin, holding the protein in clumps inside themselves. After a fixed period, typically a few hours, it's time for the harvest and the hard work of isolating the insulin from mounds of bacterial trash. The first step in the purification scheme is to separate the bacteria from the broth. That's done with a centrifuge, a machine that spins very fast, forcing the bacteria into a pellet at the bottom of a vessel. The broth is then removed and replaced with a liquid containing a substance that breaks down cell membranes, helping release the insulin from its bacterial prison.
At this point, the insulin still isn't actually insulin. It's "proinsulin," a longer inactive precursor of insulin. Insulin makers use an enzyme to carve out a section of proinsulin, leaving behind just the 51 amino acids of insulin proper. (The part that is snipped out is called C-peptide. It's a hormone in its own right, and doctors sometimes measure it in the blood of people with type 1 diabetes to see whether their bodies are still making some insulin.)
The next phase of industrial purification involves an array of giant columns made of a clear material and filled with an opaque resin. Except for their size, the columns look much like standard laboratory equipment. When describing the girth of an industrial purification column, a smiling Lilly scientist stretched his arms out widely, bringing to mind an insulin-producing Parthenon. The columns are filled with various substances designed to separate insulin from other molecules based on differences in their electrical charge, acidity, size, and other characteristics. The insulin emerges from the columns alone. At the end of its march through the mammoth columns, the insulin is quite pure. Yet, during processing, the insulin's chain of amino acids gets all tangled, rendering it inactive. To fix this, the researchers use yet another special mix of enzymes to iron out the wrinkles and get insulin into its proper form.
The final step before the insulin is ready for packaging is crystallization. The insulin is mixed with zinc, which helps it form stable crystals, and dried until it's nothing but a powder of glistening crystals. In due time, the crystals can be rehydrated in solution and poured into the vials, cartridges, and pens that are shipped around the globe.
www.diabetesforecast.org/2013/jul/making-insulin.html
global insulin sales of $16.7 billion in 2011 |
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Post by wmdhunt on Jan 25, 2016 17:52:46 GMT -5
Researchers at MIT and Harvard figured out how to produce pancreatic beta cells -- the ones that produce insulin -- in large quantities back in 2014. The same intercollegiate team announced in the journal Nature on Monday that they've now managed to implant those cells into mice that have been genetically designed to suffer from Type 1 diabetes -- without the cells being rejected. Even more impressive, the diabetic mice produced their own insulin during the 174-day study period, eliminating the need for daily injections. Instead, patients would simply need "booster" injections of beta cells once every few years.
This method "has the potential to provide diabetics with a new pancreas that is protected from the immune system," study co-author Daniel Anderson said in a statement, "which would allow them to control their blood sugar without taking drugs." Human trials are expected to begin within the next few years.
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Post by peppy on Feb 27, 2017 7:44:55 GMT -5
ingredient lists
Figure 1. Structural formula of insulin aspart.
NovoLog® is a sterile, aqueous, clear, and colorless solution, that contains
insulin aspart 100 Units/mL, glycerin 16 mg/mL, phenol 1.50 mg/mL,
metacresol 1.72 mg/mL, zinc 19.6 mcg/mL, disodium hydrogen phosphate
dihydrate 1.25 mg/mL, sodium chloride 0.58 mg/mL and water for injection.
NovoLog® has a pH of 7.2-7.6. Hydrochloric acid 10% and/or sodium
hydroxide 10% may be added to adjust pH.
www.novo-pi.com/novolog.pdf
www.chemicalland21.com/industrialchem/organic/meta-CRESOL.htm
exubera: www.screencast.com/t/uxDfbPhP www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021868s000_PharmR.pdf
Lispro: Insulin lispro has the empirical formula C257H383N65O77S6 and a molecular weight of 5808, both identical to that of human insulin.
Humalog Mix75/25 vials and Pens contain a sterile suspension of insulin lispro protamine suspension mixed with soluble insulin lispro for use as an injection.
Each milliliter of Humalog Mix75/25 injection contains insulin lispro 100 units, 0.28 mg protamine sulfate, 16 mg glycerin, 3.78 mg dibasic sodium phosphate, 1.76 mg Metacresol, zinc oxide content adjusted to provide 0.025 mg zinc ion, 0.715 mg phenol, and Water for Injection. Humalog Mix75/25 has a pH of 7.0 to 7.8. Hydrochloric acid 10% and/or sodium hydroxide 10% may have been added to adjust pH.
dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=11042
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Post by peppy on Mar 2, 2017 20:34:34 GMT -5
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Post by wmdhunt on Dec 8, 2017 9:29:39 GMT -5
Salk scientists have created a new version of the CRISPR/Cas9 genome editing technology that allows them to activate genes without creating breaks in the DNA, potentially circumventing a major hurdle to using gene editing technologies to treat human diseases. For type 1 diabetes, they aimed to boost the activity of genes that could generate insulin-producing cells. Once again, the treatment worked, lowering blood glucose levels in a mouse model of diabetes. For muscular dystrophy, the researchers expressed genes that have been previously shown to reverse disease symptoms, including one particularly large gene that cannot easily be delivered via traditional virus-mediated gene therapies. "We were very excited when we saw the results in mice," adds Fumiyuki Hatanaka, a research associate in the lab and co-first author of the paper. "We can induce gene activation and at the same time see physiological changes." Read more at: phys.org/news/2017-12-scientists-crispr-epigenetically-diabetes-kidney.html#jCp |
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Post by peppy on Dec 8, 2017 22:24:08 GMT -5
Salk scientists have created a new version of the CRISPR/Cas9 genome editing technology that allows them to activate genes without creating breaks in the DNA, potentially circumventing a major hurdle to using gene editing technologies to treat human diseases. For type 1 diabetes, they aimed to boost the activity of genes that could generate insulin-producing cells. Once again, the treatment worked, lowering blood glucose levels in a mouse model of diabetes. For muscular dystrophy, the researchers expressed genes that have been previously shown to reverse disease symptoms, including one particularly large gene that cannot easily be delivered via traditional virus-mediated gene therapies. "We were very excited when we saw the results in mice," adds Fumiyuki Hatanaka, a research associate in the lab and co-first author of the paper. "We can induce gene activation and at the same time see physiological changes." Read more at: phys.org/news/2017-12-scientists-crispr-epigenetically-diabetes-kidney.html#jCpmouse models. We Americans use media stories to run human experiments? The crisper is going to edit and activate. Volunteers to the front of the line please.
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Post by peppy on Dec 8, 2017 23:32:59 GMT -5
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