Receiving insulin. What is insulin - which organ produces the hormone, the mechanism of action in the body and indications for injections

Diabetes mellitus is one of the most common diseases in the world. In Russia, mortality from diabetes ranks third after cancer and cardiovascular diseases. The number of cases is increasing every year, disability among patients is increasing, as a result, loss of ability to work, a significant decrease in the quality of life and early mortality of patients with diabetes.

In Russia, diabetes mellitus is recognized as a socially significant disease and a huge amount of money is allocated from the budget every year to combat it. It should provide patients with preferential insulin and other sugar-containing drugs, test strips and injection syringes. In addition, every patient with diabetes has the right to count on discounted vouchers to a specialized sanatorium for treatment. Disabled people receive a special pension from the state.

The legal framework ensuring the provision of preferential medications and related medications to patients with diabetes has been prescribed Federal law“On social assistance” dated July 17, 1999 178-FZ and Government Decree No. 890 dated July 30, 1999. According to it, preferential medications are provided not only to citizens of the Russian Federation, but also to persons with a residence permit in the Russian Federation. The main benefits for type 1 and type 2 diabetics are the provision of free essential medications and insulin.

Procedure for receiving free medications and insulin

In order to receive the necessary insulin or other glucose-lowering drug for free, you must be examined by an endocrinologist at the clinic at your place of residence. Based on their analysis of the patient, the specialist writes a prescription for the required dose of the drug. It is important to remember that prescriptions for reduced-price insulin are written out by an endocrinologist every month and given to the patient personally. A doctor does not have the right to write a prescription with a dose of medication exceeding monthly norm. Or write a prescription online. This is done to carefully monitor the patient’s treatment and the doses of medications he takes. And also in order to prevent irrational use of drugs. Depending on the course of the disease and a number of associated factors, the dosage of the medication may vary according to the blood sugar level.

To obtain a prescription for insulin, the patient must have a passport, insurance certificate, medical policy, disability certificate or any other document that would confirm the right to use subsidized insulin. You must also have a certificate from the Pension Fund with you indicating that you have not waived the benefits provided by the state.

A doctor has no right to refuse to issue a prescription to a patient for a vital, subsidized drug. Preferential drugs are financed directly from the country's budget and the administration's arguments that the medical institution is not sufficiently provided for are not convincing - the drugs are paid for by the state, not the clinic.

Insulin can be obtained from pharmacies with which the medical institution has entered into an agreement. Their addresses are provided to the patient by the doctor who wrote the prescription. If the patient is in force various circumstances If you didn’t make it to your doctor’s appointment on time and were left without a prescription for insulin, you can buy it at the pharmacy for money.

The validity period of the form for the provision of medicines and insulin can vary from two weeks to a month, this must be indicated in the prescription. If the patient himself needs to come to pick up the prescription, then a relative or representative of the patient can come to the pharmacy with the prescription in hand.

What to do if you are denied free insulin

Unfortunately, patients with diabetes do not always have the opportunity to exercise their legal right to purchase subsidized insulin. The most harmless reason why a patient cannot get insulin is because it is temporarily unavailable at the pharmacy. In this case, the patient must register social magazine the pharmacist has the document number giving the right to receive free insulin. Within ten days after this, the medicine must be given to the patient. If for some reason this cannot be done, the pharmacy administration is obliged to warn the patient and refer him to other retail outlets.

If the pharmacy has all prescription drugs, but refuses to provide them free of charge, then you should contact the Compulsory Health Insurance Fund, its regional department. This is an organization that is obliged to monitor the observance of the rights of patients, including those with diabetes, in the field of medical care. You should always require a refusal to be formalized writing indicating the reason for refusal, date, signature and seal of the organization. It is not always possible to obtain such registration, if only due to the fact that not all employees have the right to store and use the seal and details of the organization. But, as a rule, the requirement to put the refusal in writing leads to a quick resolution of the conflict and the provision of the necessary medications or information on how to obtain them elsewhere.

If you lose your insulin prescription, you should see the doctor who wrote the previous prescription again as soon as possible. The doctor will write out a new form and report the loss to the pharmaceutical company. This is done in order to completely eliminate the illegal use of drugs.

If the doctor himself refuses to issue a prescription to the patient, then it is worth contacting the head physician for clarification. If the clinic administration refuses the patient’s prescription, a written refusal should be requested. The request can be oral, but it is better to make it in writing in two copies, one of which should bear the medical institution’s mark on incoming correspondence. The medical institution is obliged to respond within the time limits established by law. You also need to contact the Compulsory Health Insurance Fund with a statement about the medical institution’s failure to comply with its obligations to provide prescriptions for subsidized medications. You can contact the Ministry of Health or the social protection authorities with a request to understand the situation. All requests must be in writing and each copy must be marked with registration of correspondence from the institution where the request was received. If there is no response within a month, you need to send a complaint to the Prosecutor's Office, the Commissioner for Human Rights with a request to suppress the violation of the rights of a diabetic patient in providing preferential insulin.

According to the latest statistics, almost 300 million people on Earth suffer from diabetes in one form or another, of which almost half are insulin dependent. This means that without the timely introduction of the required dose of insulin into the body, a person may experience irreparable structural changes in the body, which can lead to death. For a patient with insulin-dependent type 1 diabetes, it is always important to have small stock insulin in case of unforeseen situations. It is important to strictly follow a diet to avoid sudden spikes in blood sugar. Required physical exercise. Muscles not only burn excess sugar, but also help improve blood circulation in the extremities, an area at risk for gangrenous changes in all diabetic patients. The strictest discipline and knowledge of their rights will help patients with insulin-dependent diabetes in correcting the disease and maintaining normal level life.

Insulin is a hormone that plays vital role in ensuring the normal functioning of the human body. It is produced by pancreatic cells and promotes the absorption of glucose, which is the main source of energy and the main nutrition for the brain.

But sometimes, for one reason or another, insulin secretion in the body decreases noticeably or stops altogether, what to do about it and how to help. This leads to severe disruption of carbohydrate metabolism and the development of such dangerous disease like diabetes.

Without timely and adequate treatment, this disease can lead to serious consequences, including loss of vision and limbs. The only way to prevent the development of complications is regular injections of artificially produced insulin.

But what is insulin for diabetics made from and how does it affect the patient’s body? These questions interest many people diagnosed with diabetes. To understand this, it is necessary to consider all methods of obtaining insulin.

Varieties

Modern insulin preparations differ in the following ways:

• Source of origin;
• Duration of action;
• pH of the solution (acidic or neutral);
• The presence of preservatives (phenol, cresol, phenol-cresol, methylparaben);
• Insulin concentration - 40, 80, 100, 200, 500 U/ml.

These signs influence the quality of the drug, its cost and the degree of impact on the body.

Sources

Sugar level

Depending on the source of production, insulin preparations are divided into two main groups:

Animals. They are obtained from the pancreas glands of large cattle and pigs. They can be unsafe, as they often cause serious allergic reactions. This is especially true for bovine insulin, which contains three amino acids not found in humans. Porcine insulin is safer, as it differs by only one amino acid. Therefore, it is more often used in treatment diabetes mellitus.

Human. They come in two types: similar to human or semi-synthetic, obtained from pork insulin by enzymatic transformation, and human or DNA recombinant, which are produced by E. coli bacteria thanks to the achievements of genetic engineering. These insulin preparations are completely identical to the hormone produced by the human pancreas.

Today, insulin of both human and animal origin is widely used in the treatment of diabetes mellitus. Modern production animal insulin requires the highest degree of purification of the drug.

This helps rid it of unwanted impurities such as proinsulin, glucagon, somatostatin, proteins, polypeptides, which can cause serious side effects.

The best drug of animal origin is considered to be modern monopeak insulin, that is, produced with the release of a “peak” of insulin.

Duration of action

The production of insulin is carried out using different technologies, which makes it possible to obtain drugs of various durations actions, namely:

• ultra short acting;
• short acting;
• prolonged action;
• average duration of action;
• long-acting;
• combined action.

Ultra-short-acting insulins. These insulin preparations are distinguished by the fact that they begin to act immediately after the injection and reach their peak after 60-90 minutes. Their total duration of action is no more than 3-4 hours.

There are two main types of ultra-short-acting insulin - Lispro and Aspart. Insulin Lispro is produced by rearranging two amino acid residues in the hormone molecule, namely lysine and proline.

Thanks to such a modification of the molecule, it is possible to avoid the formation of hexamers and accelerate its breakdown into monomers, which means improving the absorption of insulin. This makes it possible to obtain an insulin preparation that enters the patient’s blood three times faster than natural human insulin.

Another ultra-short-acting insulin is Aspart. The methods for producing insulin Aspart are in many ways similar to the production of Lispro, only in this case proline is replaced with negatively charged aspartic acid.

Just like Lispro, Aspart quickly breaks down into monomers and is therefore almost instantly absorbed into the blood. All ultra-short-acting insulin preparations can be administered immediately before or immediately after meals.

Short-acting insulins. These insulins are buffer solutions with a neutral pH (6.6 to 8.0). They are recommended to be administered as, but if necessary, it is allowed to use intramuscular injections or droppers.

These insulin drugs begin to act within 20 minutes after entering the body. Their effect lasts relatively short - no more than 6 hours, and reaches its maximum after 2 hours.

Short-acting insulins are mainly produced for the treatment of patients with diabetes mellitus in a hospital setting. They effectively help patients with diabetic coma and coma. In addition, they allow you to most accurately determine the required dose of insulin for the patient.

Intermediate-acting insulins. These drugs dissolve much less well than short-acting insulins. Therefore, they flow blood more slowly, which significantly increases their hypoglycemic effect.

Obtaining insulin with an average duration of action is achieved by introducing into their composition a special prolongator - zinc or protamine (isophane, protafane, basal).

Such insulin preparations are available in the form of suspensions, with a certain amount of zinc or protamine crystals (most often Hagedorn protamine and isophane). Prolongators significantly increase the time of absorption of the drug from subcutaneous tissue, which significantly increases the time for insulin to enter the blood.

Long-acting insulins. This is the most modern insulin, the production of which became possible thanks to the development of DNA recombinant technology. The very first long-acting insulin drug was Glargine, which is an exact analogue of the hormone produced by the human pancreas.

To obtain it, a complex modification of the insulin molecule is carried out, involving the replacement of asparagine with glycine and the subsequent addition of two arginine residues.

Glargine is available in the form of a clear solution with a characteristic acidic pH of 4. This pH makes insulin hexamers more stable and thereby ensures long-term and predictable absorption of the drug into the patient’s blood. However, due to the acidic pH of Glargine, it is not recommended to combine it with short-acting insulins, which usually have a neutral pH.

Most insulin drugs have a so-called “peak action”, at which the highest concentration of insulin is observed in the patient’s blood. However, the main feature of Glargine is that it does not have a clear peak of action.

Just one injection of the drug per day is enough to provide the patient with reliable peak-free glycemic control for the next 24 hours. This is achieved due to the fact that Glargine is absorbed from the subcutaneous tissue at the same rate throughout the entire period of action.

Long-acting insulin preparations are manufactured in various forms and can provide the patient with a hypoglycemic effect for up to 36 hours in a row. This helps to significantly reduce the number of insulin injections per day and thereby significantly make life easier for diabetics.

Combined drugs. These drugs are available in the form of a suspension, which includes a neutral solution of short-acting insulin and intermediate-acting insulins with isophane.

Such drugs allow the patient to introduce insulins of varying durations of action into his body with just one injection, which means avoiding additional injections.

Disinfection of insulin preparations is of great importance for the safety of the patient, since they are injected into his body and spread throughout the bloodstream throughout the body. internal organs and fabrics.

Some substances that are added to insulin not only as a disinfectant, but also as preservatives have a certain bactericidal effect. These include cresol, phenol and methyl parabenzoate. In addition, a pronounced antimicrobial effect is also characteristic of zinc ions, which are part of some insulin solutions.

Multi-level protection against bacterial infection, which is achieved by adding preservatives and other antiseptics, helps prevent the development of many severe complications. After all, repeated insertion of a syringe needle into a vial of insulin could cause contamination of the drug with pathogenic bacteria.

However, the bactericidal properties of the solution help destroy harmful microorganisms and maintain its safety for the patient. For this reason, diabetic patients can use the same syringe to perform subcutaneous insulin injections up to 7 times in a row.

Another advantage of having preservatives in insulin is that there is no need to disinfect the skin before the injection. But this is only possible with the use of special insulin syringes equipped with a very thin needle.

It must be emphasized that the presence of preservatives in insulin does not have any effect negative influence on the properties of the drug and is completely safe for the patient.

Conclusion

Today, insulin, produced both using the pancreas of animals and modern genetic engineering methods, is widely used to create a large number of drugs.

The most preferred for daily insulin therapy are highly purified DNA-recombinant human insulins, which are characterized by the lowest antigenicity, and therefore practically do not cause allergic reactions. Besides, high quality drugs created on the basis of analogs of human insulin are safe.

Insulin preparations are sold in glass bottles of various capacities, hermetically sealed with rubber stoppers and covered with aluminum lining. In addition, they can be purchased in special insulin syringes, as well as syringe pens, which are especially convenient for children.

Currently, fundamentally new forms of insulin preparations are being developed, which will be introduced into the body intranasally, that is, through the nasal mucosa.

It has been found that by combining insulin with a detergent, it is possible to create an aerosol preparation that would reach the required concentration in the patient’s blood as quickly as with an intravenous injection. In addition, new oral insulin preparations are being created that can be taken by mouth.

Insulin-dependent diabetes is a disease that requires lifelong therapy. The patient’s life literally depends on the presence or absence of insulin.
Diabetes is officially recognized as a non-infectious epidemic and, according to WHO, ranks third in terms of prevalence after cardiovascular diseases and cancer. There are 200 million people with diabetes in the world, which is already 6% of the world's adult population. More than 2.7 million of them live in our country. Their lives largely depend on what is produced within these walls.

The Medsintez plant has been operating in Sverdlovsk Novouralsk since 2003. Today it satisfies 70% of the total needs Russian market insulin. So I took the opportunity to take a short tour of this enterprise with pleasure and interest.
And the first thing that surprised me was the “matryoshka” buildings. Inside the production “non-sterile” workshop there is another “clean” one. Of course, in the common corridors there are mirrored floors and cleanliness everywhere. But the main action takes place there, behind the glass windows.

LLC "Plant Medsintez", created in 2003, is part of the NP "Ural Pharmaceutical Cluster". Today the cluster unites 29 companies of various profiles with a total staff of more than 1,000 people. The plant currently employs more than 300 people.

Guests were not allowed inside, even though we were packed in overalls. I had to look through the windows.

Inside, female manual labor dominates. Something is being laid out and packed.

And even though you realize that everything is safe inside and medicines are being produced, you still somehow feel uneasy.

So what are those beautiful eyes opposite doing at work?
In a nutshell, or rather in one picture, here it is:

INSULIN PRODUCTION SCHEME

Now to the point. In 2008 at the Medsintez plant with the participation of the governor Sverdlovsk region E.E. Rossel, the opening of Russia's first industrial production of finished dosage forms of genetically engineered human insulin took place in accordance with GMP EC requirements (TUV NORD certificate No. 04100 050254/01).
The capacity of the production site is up to 10 billion IU per year, which allows satisfying up to 70% of the needs of the Russian insulin market.

The production is located in a new building with an area of ​​more than 4000 m². It includes a complex of clean rooms with an area of ​​386 m², including rooms of cleanliness classes A, B, C and D.
The production equipment is equipped with technological equipment from the world's leading manufacturers: BOSCH (Germany), SUDMO (Germany), GF (Italy), EISAI (Japan).

However, the substance needed to produce the drug previously had to be purchased in France. In order to produce the substance ourselves, it was necessary to develop our own bacteria. This took Ural scientists four years - they patented their strain in May 2012. Now the matter is to expand production. In the meantime, we were shown the holy of holies - this is the substance where the production chain begins.

Ural Plenipotentiary Igor Kholmanskikh and accompanying persons listen short description workflow.

On the other side of the glass are bioreactors. Everything is automated and people are only on this side.

“Live” employees can only be seen further down the technological chain. Water treatment workshop.

The drugs themselves are moved from workshop to workshop exclusively on conveyors.

Here the girls are collecting packages and putting them on a transport belt.

The conveyor approaches the border of the “sterile” zone and dumps the packages into a special tray.

Knocked out of the tray along with the packages powerful flow air. Bacteria and other nasty things can't get through.

There they are put on pallets and sent to this huge purifier.

It’s also deserted, or rather there’s only one operator working. The trolleys roll automatically on rails.

Now the last section is packaging into transport containers. Insulin is ready to go to the consumer. There are not many people either, even the boxes are laid out by a creepy machine on servos.

A new building is being built in Novouralsk, which should completely cover the need for insulin substance for the entire country. Moreover, some of the products will be supplied abroad - agreements on this have already been signed.

The new building will go into operation in a few months. Medsintez expects to receive the first batch of entirely Russian insulin in the first half of 2013.
The cost of the project for the construction of a new building is 2.6 billion rubles. The workshop area is 15 thousand square meters. m, of which 2 thousand are laboratories. Most of the equipment will be purchased in Germany. The plant's capacity should be 400 kg of the substance per year. This, according to experts, exceeds the need of the Russian Federation by 75 kg.

Today, about 2 million Russians need to take insulin daily. A package of a foreign drug costs about 600 rubles, a domestic one - about 450–500 rubles. After the project is completed, the cost should drop to 300 rubles. Savings to the Russian budget could amount to approximately 4 billion rubles.

Insulin is a pancreatic hormone that plays a vital role in the body. It is this substance that promotes adequate absorption of glucose, which in turn is the main source of energy and also nourishes brain tissue.

Diabetics who are forced to take the hormone by injection sooner or later think about what insulin is made from, how one drug differs from another, and how artificial analogues of the hormone affect a person’s well-being and the functional potential of organs and systems.

Differences between different types of insulin

Insulin is a vital drug. People suffering from diabetes cannot do without this remedy. The pharmacological range of medications for diabetics is relatively wide.

The drugs differ from each other in many aspects:

Every year in the world, leading pharmaceutical companies produce colossal amounts of “artificial” hormone. Insulin manufacturers in Russia also contributed to the development of this industry.

Every year, diabetics around the world consume over 6 billion units of insulin. Given the negative trends and the rapid increase in the number of patients with diabetes, the need for insulin will only increase.

Sources for obtaining the hormone

Not every person knows what insulin for diabetics is made from, but the origin of this most valuable drug is really interesting.

Modern insulin production technology uses two sources:

• Animals. The drug is obtained by treating the pancreas of cattle (less commonly), as well as pigs. Bovine insulin contains as many as three “extra” amino acids, which are foreign in their biological structure and origin to humans. This can cause the development of persistent allergic reactions. Porcine insulin is distinguishable from the human hormone by only one amino acid, which makes it much safer. Depending on how insulin is produced and how thoroughly the biological product is purified, the degree to which the drug is accepted by the human body will depend;
• Human analogues. Products in this category are manufactured according to the most complex technologies. Leading pharmaceutical companies have established bacterial production of human insulin in medicinal purposes. Enzymatic transformation techniques are widely used to obtain semi-synthetic hormonal products. Another technology involves the use of innovative genetic engineering techniques to obtain unique DNA recombinant insulin formulations.

How insulin was obtained: the first attempts of pharmacists

Drugs obtained from animal sources are considered drugs produced using old technology. Medicines are considered to be of relatively low quality due to insufficient purification final product. In the early 20s of the last century, insulin, even though it caused severe allergies, became a real “pharmacological miracle” that saved the lives of insulin-dependent people.

The first releases of the drugs were also difficult to tolerate due to the presence of proinsulin in the composition. Hormonal injections were particularly poorly tolerated by children and the elderly. Over time, this impurity (proinsulin) was removed by more thorough purification of the composition. They abandoned bovine insulin altogether, as it almost always caused side effects.

What is insulin made of: important nuances

In modern therapeutic regimens for patients, both types of insulin are used: both animal and human origin. The latest developments make it possible to produce products of the highest degree of purification.

Previously, insulin could contain a number of undesirable impurities:

Previously, such “supplements” could cause serious complications, especially in patients who were forced to take large doses of the drug.

Improved medicines are free of unwanted impurities. If we consider insulin of animal origin, the best product is the monopeak product, which is produced with the production of a “peak” of the hormonal substance.

Duration of pharmacological effect

The production of hormonal drugs has been established in several directions at once. Depending on how the insulin is made will determine how long it lasts.

The following types of drugs are distinguished:

Ultra-short-acting drugs

Ultra-short-acting insulins act literally in the first seconds after administration of the drug. The peak of action occurs after 30 - 45 minutes. The total time of exposure to the patient’s body does not exceed 3 hours.

Typical representatives of the group: Lizpro and Aspart. In the first version, insulin is produced by rearranging amino acid residues in the hormone (we are talking about lysine and proline). In this way, the risk of hexamers occurring during production is minimized. Due to the fact that such insulin quickly breaks down into monomers, the process of absorption of the drug is not accompanied by complications and side effects.

Aspart is produced in a similar way. The only difference is that the amino acid proline is replaced with aspartic acid. The drug quickly breaks down in the human body into a number of simple molecules and is instantly absorbed into the blood.

Short-acting drugs

Short-acting insulins are presented in buffer solutions. They are intended specifically for subcutaneous injections. In some cases, a different format of administration is allowed, but such decisions can only be made by a doctor.

The drug begins to “work” after 15 – 25 minutes. The maximum concentration of the substance in the body is observed 2 - 2.5 hours after injection.

In general, the drug affects the patient’s body for about 6 hours. Insulins of this category are created for the treatment of diabetics in a hospital setting. They allow you to quickly remove a person from a state of acute hyperglycemia, diabetic precoma or coma.

Intermediate-acting insulin

The drugs slowly enter the bloodstream. Insulin is received by standard scheme, but at the final stages of production the composition is improved. To increase their hypoglycemic effect, special prolonging substances - zinc or protamine - are added to the composition. Most often, insulin is presented in the form of suspensions.

Long acting insulin

Long-acting insulins are the most modern pharmacological products today. The most popular drug is Glargine. The manufacturer has never hidden what human insulin for diabetics is made from. Using DNA recombinant technology, it is possible to create an exact analogue of the hormone that is synthesized by the pancreas of a healthy person.

To obtain the final product, an extremely complex modification of the hormone molecule is carried out. Replace asparagine with glycine, adding arginine residues. The drug is not used to treat comatose or precomatous conditions. It is prescribed only subcutaneously.

The role of excipients

It is impossible to imagine the production of any pharmacological product, in particular insulin, without the use of special additives.

Auxiliary components help improve the chemical qualities of the drug, as well as achieve the maximum degree of purity of the composition.

According to their classes, all additives for insulin-containing drugs can be divided into the following categories:

1. Substances that predetermine the prolongation of drugs;
2. Disinfecting components;
3. Acidity stabilizers.

Prolongators

In order to extend the time of exposure to the patient, prolonging drugs are added to the insulin solution.

Most often used:

Antimicrobial components

Antimicrobial components extend the shelf life of medications. The presence of disinfecting components helps prevent the proliferation of microbes. These substances, by their biochemical nature, are preservatives that do not affect the activity of the drug itself.

The most popular antimicrobial additives used in insulin production are:

Each specific drug uses its own special additives. Their interaction with each other is necessarily studied in detail at the preclinical stage. The main requirement is that the preservative must not violate biological activity drug.

A high-quality and skillfully selected disinfectant allows you not only to maintain the sterility of the composition over a long period, but even to make intradermal or subcutaneous injections without first disinfecting the dermal tissue. This is extremely important when extreme situations when there is no time to treat the injection site.

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Insulin is a substance that is produced in the pancreas (“islets of Langerhans”). This hormone is of key importance in metabolism in almost all tissues of the body, as it ensures the openness of cell membranes to glucose components. Until insulin was produced synthetically, many patients with diabetes were doomed to death, since glucose is used to produce all types of molecules containing carbon and represents the only source of energy for mitochondria. In the absence of insulin, the cell membrane allows a tiny amount of glucose to pass through, which leads to cell death from lack of nutrition.

Absolute and relative insulin deficiency

Diabetes, as we know, comes in two types. The first type occurs when a person has destruction in the beta cells of the above-mentioned “islands of Langerhans”. This is an absolute deficiency of insulin. Diabetes of the second type develops with relative insulin deficiency - the incorrect effect of insulin on one or another type of tissue. The Russian doctor I.M. suggested that blood sugar levels are regulated by some hormone in the pancreas. Sobolev in the mid-19th century. Somewhat later, P. Langerhans established that there are some special areas in the gland, and O. Minkovsky and D. Mehring established a connection between these “islands” and blood sugar levels during experiments on dogs. It took about 20 years to extract from the “islets of Langerhans” what they produce and attempts to administer the resulting substances in the form of aqueous solutions to the same dogs. It must be said that experiments in curing diabetic conditions in four-legged friends were successful by 1916, but their development was interrupted by the First World War(works by N. Paulescu).

During F. Banting's experiments on dogs, the animals' pancreas was operated on in such a way that most of it degenerated, leaving only areas with Langerhans cells. After a series of experiments, Banting decided to take the fetal pancreas of a calf, which did not yet contain digestive glands, to prepare extracts, and the resulting substance was tested on 14-year-old L. Thompson, who suffered a severe allergic reaction due to the by-products. D. Collip undertook to clear the impurities, as a result of which the first insulin was isolated, which brought back a ten-year-old boy from a coma. In a similar way, insulin is obtained today in some countries from the pancreas of cattle (bovine) or pigs. From 1 kg of substance you can extract 0.1 g of insulin.

Technologies of the last century

For production, crushed (often frozen) raw materials are subjected to acid-alcohol extraction (two-stage treatment with acidified ethyl alcohol), after which the results of the chemical reaction are neutralized and subjected to a salting out procedure - separation from solution by adding another substance, most often zinc salts. The solution is crystallized and dried. The extract after such manipulations contains about 90% insulin. The remaining shares are occupied by additional substances:

• pancreatic polypeptide;
• glucagon;
• proinsulin;
• somatostatin.

These elements make the resulting drug immunogenic, that is, the human body produces antibodies, causing allergic reactions. The immunogenicity of the drug is based mainly on proinsulin, which is a precursor of insulin itself and contains an additional molecule (C-peptide), which has various modifications in different living beings.

Therefore, the resulting substance was subjected to repeated processing in the form of dissolution and recrystallization, which made it possible to increase the insulin content to a level of more than 90% (standard degree of purification). It must be said that the drug obtained from the pancreas of ungulates is less suitable for humans than insulin extracted from the insides of a pig. Insulin itself consists of 51 amino acids, of which 3 are not the same in humans and ungulates (this is supposed to be due to the vegetarian diet of bulls), and in humans and, most likely, the omnivorous pig, there is only one amino acid. Therefore, bovine insulin (and its mixtures with pork) are not prescribed to patients with diabetes mellitus in the early stages of the disease, pregnant women, and during short-term therapy (for example, postoperative). It can cause a wide variety of adverse reactions, including changes in subcutaneous fatty tissue at the injection sites.

Monocomponent insulin

After the discovery of insulin, doctors and scientists faced the question of increasing the degree of its purification to reduce allergic reactions of patients. To do this, the above extract of standard purity is sent to chromatography (usually liquid) during which monopeak insulin (including monodeamino-monoaggregin- and monoethylinsulins) is formed on the walls of the equipment. If the resulting substance is subjected to chromatography several times, you will get monocomponent insulin, which gives significantly less side effects, and also has high activity. Such insulins are usually marked “MS” on the bottle.

How is insulin obtained in the 21st century? The above semi-synthetic method, when the feedstock goes through many stages of purification, is still not outdated. The disadvantage in this case is the dependence on supplies from livestock farms. Two other methods - a full chemical cycle or production from human pancreases - are not possible due to uneconomical and unethical use of human tissue. Therefore, since the end of the 20th century, Western companies (Hoechst, Novo Nordisk, Eli Lilly, Aventis) have mastered and patented biosynthetic technology based on genetic engineering.

The role of E. coli and yeast in insulin generation

A description of the process of producing insulin through biological synthesis is as follows: general outline roughly as follows: the isolated human insulin genome is introduced into the genome of Escherichia coli, which quickly synthesizes proinsulin, from which the C-peptide enzyme is then cleaved off (Eli Lilly technology). Novo Nordisk produces the hormone in a slightly different way. Here they created an artificial miniproinsulin gene, which has a C-peptide “tail”. It is significantly shorter than the insulin required for the medication. The gene is placed in a baker's yeast cell, which divides to generate the required volumes of raw materials. After which the mini C-peptide is removed from the resulting material and a substance with high degree purification identical to human insulin.

The Aventis Corporation takes as a basis the gene from macaque monkeys, whose insulin is the same as human insulin. Using template ribonucleic acid, DNA is cloned from this gene and introduced into E. coli cells. The main task of manufacturing companies is complete cleaning the finished product from impurities in the form of traces of the activity of microorganisms and the remains of the organisms themselves. Modern methods production controls allow this to be done so effectively that biosynthetic insulin is almost identical from the world's main suppliers.

Period of action of drugs

At the dawn of its appearance, insulin had enough short term action (began to act after 15-40 minutes, but “worked” for no more than 1.5-4 hours), which led to the need to create long-acting drugs. In their chemical composition included protamine (protein, extracted from fish milk, has an alkaline reaction), phosphate buffer (maintaining a neutral pH level) and zinc, as well as phenol (creazone) to ensure the crystallization process. The result of these additions was NPH insulin.

After scientists discovered that adding small amounts of zinc under neutral pH conditions prolongs the period, insulin-zinc suspension (IZS) was invented, the first dosage form of which was Lente insulin. It and its subsequent analogues made it possible to obtain a therapeutic effect in 6-8 hours for intermediate-acting insulin and in 8-10 hours for long-acting insulin. However, we must remember that intermediate- and long-acting insulin begins to “work” after 2 and 4 hours and lasts for 6-8 and 8-10 hours, respectively.

Therefore, each diabetic patient must have an individual round-the-clock insulin regimen.

Insulin as ready medicinal product also contains preservatives and disinfectants. These are creson and phenol (if they are present, the medicine smells unpleasant), methylparaben, zinc ions. Each dosage form contains its own disinfectant component. For example, phenol is not added to the ISC, since it changes physical properties insulin (methyl parabenzoate is used in ISC). In addition, the preparations contain ingredients that give buffer properties and convert insulin into a crystalline state. For ISC this is NaCl, for other dosage forms it is phosphates. Patients can receive insulin in different forms, including aerosol, solution, or suspension. The medicine can be either pH neutral or acidic. Standard release concentrations are: 500 units/ml, 250, 100, 80 and 40.

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Comments

Megan92 () 2 weeks ago

Has anyone managed to completely cure diabetes? They say it is impossible to completely cure...

Daria () 2 weeks ago

I also thought it was impossible, but after reading this article, I had long since forgotten about this “incurable” disease.

Megan92 () 13 days ago

Daria () 12 days ago

Megan92, that’s what I wrote in my first comment) I’ll duplicate it just in case - link to article.

Sonya 10 days ago

Isn't this a scam? Why do they sell on the Internet?

Yulek26 (Tver) 10 days ago

Sonya, what country do you live in? They sell it on the Internet because stores and pharmacies charge outrageous markups. In addition, payment is only after receipt, that is, they first looked, checked and only then paid. And now they sell everything on the Internet - from clothes to TVs and furniture.

Editor's response 10 days ago

Sonya, hello. This drug for the treatment of diabetes mellitus is indeed not sold through the pharmacy chain in order to avoid inflated prices. Currently you can only order from official website. Be healthy!

Sonya 10 days ago

I apologize, I didn’t notice the information about cash on delivery at first. Then everything is fine if payment is made upon receipt.