New Ming Empire mixed in America

PS: Reposted from Tieba

Why do I say it’s impossible for me? Let’s not talk about other things, just talk about the production volume, you may not be able to achieve it.

The first and most important thing is whether you can get a high-yielding strain. The yield of modern high-yielding strains is more than 20,000 times that of the earliest penicillin strain discovered by Fleming. Modern strains are produced by ultraviolet mutagenesis and then screened. Each

Basically, the company’s mature strains are kept secret, can you get it?

If you want to rely on natural mutants, the best natural mutant comes from rotten cantaloupes on a farm in the United States. The yield is roughly 200 times that of Fleming's earliest strain.

When Fleming prepared penicillin for clinical trials in the early days, he could only produce a dosage (15,000 units) for one patient once every month. For the convenience of discussion, let’s assume that our safety point is the same as that of Fleming.

Laming's experimental conditions are the same (in fact most of the safe points are impossible to achieve #(funny))

According to research in 1943-1944, penicillin treatment for diplococcus gonorrhoeae requires 100,000-150,000 units administered within 24-48 hours (95% cure rate); treatment of arthritis, peritonitis, or other systemic diseases requires 100,000 units daily

10,000-200,000 units, lasting 5-7 days.

Let me first make a general assumption that the penicillin you plan to produce is mainly used to treat general infections. For every person cured, a total of 300,000 units will be consumed. (This consumption is already very low, because there is still drug resistance)

Assuming that the best strains in nature are used (200 times), then 3 million units can be produced per month and only 10 people can be treated. Note! This can be said to be the level of early industrial production of penicillin. If a small group specializes in this direction

Maybe it can still be achieved. If an individual can have one person per month, he will be invincible. Why? Let’s continue talking.

There are several major difficulties in producing penicillin. Let’s briefly talk about them.

Sterile

Some people are probably going to criticize me after reading this. Isn’t penicillin sterilizing? What the hell? Because penicillin mainly targets bacteria and has very little killing effect on its similar fungi. Many harmful molds can coexist with penicillium, and they secrete mycotoxins

Some are very toxic. What’s even more annoying is that many mycotoxins are very stable and cannot be inactivated when heated to 180 degrees Celsius (such as the toxins of some poisonous mushrooms). Therefore, Penicillium that does not grow from a single colony must not be used indiscriminately.

, the previous poster’s walnut... If you use it as a bacterial strain, it will definitely be cold. Penicillin bacteria are typical aerobic bacteria and have a huge demand for oxygen, so air must be continuously introduced during the growth process.

For this, the air must be sterilized. How to do this in a safe place?

Temperature, humidity, pH control

Penicillium fermentation requires temperature control between 20-24 degrees Celsius. Compared with temperature, the humidity of fermentation is less important. pH is another important point. The optimal growth pH of Penicillium is 6.5. Once it exceeds 8, it will easily die.

.However, the metabolites of Penicillium are alkaline, so the pH value in the fermentation device rises very quickly. One of the early production exploration directions was to stabilize the pH value of the culture solution to facilitate long-term production, but this effort failed shamefully.

Therefore, the short-term production method is commonly used: the pH is not controlled after the fermentation starts, but the pH changes are monitored, and the fermentation is terminated when pH=8. This is different from the long-term continuous production of many pharmaceuticals (which also significantly increases the cost).

Normally, penicillin begins to be produced on the 2nd to 3rd day of fermentation, and the pH value reaches the limit after 4 to 5 days. The entire period lasts for 7 to 8 days. This period of time cannot be said to be too short, and valuable labor is used.

Go and take care of it#(Ah)

Moreover, the fermentation medium I found contained these things

1% glucose solution

80% alcohol

1% lactose

1% calcium carbonate

0.4% sodium hydrogen phosphate

1.5g/L potassium dihydrogen phosphate

5g/L potassium sulfate

12g/L ammonium sulfate

8.5% corn fermentation liquid

Anti-foam agent

Phenylacetic acid (if it has it, it can produce penicillin G, if it doesn't have it, it can only produce penicillin K, its antibacterial spectrum is relatively narrow)

These are all consumables, how many do you need to prepare?

Assume that we have prepared a complete set of fermentation equipment at a safe point and successfully produced with quality and quantity. Don’t be too happy too early. There is still purification waiting for you# (funny)

When pH=2 (moderately acidic), penicillin can be extracted from the filtered bacterial solution into ether, n-amyl acetate or other similar organic solvents. However, when pH=2, penicillin loses very quickly at room temperature.

Therefore, this extraction process must be completed at 4-5 degrees Celsius, and the faster, the better, because even at 4 degrees Celsius, penicillin still deactivates very quickly (4-5 hours,

70% deactivation), so this step must use a centrifuge (to separate and remove all insoluble impurities). After the penicillin is extracted into the organic solvent, add an aqueous solution with a pH between 6-7 and shake vigorously.

Extract the penicillin back into the aqueous phase.

And this step is just a crude extraction. The Penicillium culture medium will also produce pyrogen, which cannot be removed by the crude extraction step. It just depends on your luck...

There are two ways to go about crude extraction products:

A. Use some method to detect the pyrogen content of each batch

This method is feasible, but it requires the consumption of experimental animals, and it is safer to keep mice inside. Although it can also be used as a source of meat, cultivating mice for experiments is also a troublesome matter.

B. Further purification

Brother, you are doing something crazy

In fact, the production of antibiotics is very complicated. Many of the homemade methods are just gambling on luck, and the conditions for serious production are too complicated. Historically, on September 5, 1944, my country successfully developed penicillin on its own, becoming the first There were only 5 bottles produced in the batch, each with 5,000 units. Two bottles were sent to Chongqing, and two bottles were sent to the United Kingdom and the United States for appraisal. Both were well received. The remaining bottle was kept by themselves and is said to be still treasured in the Antibiotic Research Center of the Chinese Academy of Medical Sciences. Place.

I personally feel that the safety of most people cannot reach the level of our country's laboratories in 1944. Are there any people who have confidence in making usable penicillin using local methods? (Happy)? In addition to improving physical fitness, I still stock up.

Huoba#(funny)