Insulin soluble human genetically engineered and all about it.

Human insulin refers to hormones that are produced in the pancreas. It is used for therapy diabetes. To simulate the normal activity of the pancreas, the patient is given insulin injections:

short-term influence;
lasting impact;
medium duration actions.

The type of drug is determined based on the patient's well-being and the type of disease.

Types of insulin

Insulin was first made from the pancreas of dogs. A year later, the hormone was already injected into practical use. Another 40 years passed, and it became possible to synthesize insulin chemically.

After some time, funds were made with high level cleaning. A few more years later, experts began developing the synthesis of human insulin. Beginning in 1983, insulin began to be produced on a production scale.

Even 15 years ago, diabetes was treated with products made from animals. Nowadays it is prohibited. In pharmacies, you can only find genetic engineering drugs, the manufacture of these drugs is based on the transplantation of a gene product into a cell of a microorganism.

For this purpose, yeast or a non-pathogenic type of bacteria are used. coli. As a result, microorganisms begin to produce insulin for humans.

The difference between all medical means available today is:

in time of exposure, long-term insulins, ultra short action and short-acting insulin.
in the amino acid sequence.

There are also combined products, called “mixes”, in their composition it is present as insulin long-acting, and of short duration. All 5 types of insulin are used as directed.

Short acting insulin

Insulins of a short duration, sometimes ultrashort, are solutions of crystalline zinc-insulin in a complex with a neutral pH type. These drugs have a quick effect, however, the effect of the drugs is short-lived.

As a rule, such funds are administered subcutaneously 30-45 minutes before meals. Such medications can be administered both intramuscularly and intravenously, as well as long-acting insulin.

With the penetration of an ultrashort agent into a vein, the level of sugar in the plasma decreases sharply, the effect can be observed after 20-30 minutes.

Soon the blood will be cleared of the drug, and hormones such as catecholamines, glucagon and growth hormone will increase the amount of glucose to its original level.

In case of violations of the production of contrainsular hormones, the blood sugar level does not increase for several hours after the injection medical device, because it has an effect on the body even after removal from the blood.

The hormone of short influence must be injected into a vein:

during resuscitation and intensive treatment;
patients with diabetic ketoacidosis;
if the body rapidly changes its need for insulin.

In patients with stable diabetes mellitus, such drugs are usually taken in combination with long-acting and medium-acting drugs.

Ultrashort-acting insulin is an exceptional medical product that a patient can have with him in a special dispenser.

Buffered agents are used to charge the dispenser. This prevents the insulin from crystallizing under the skin in the catheter during a rather slow injection.

Today, the short-term hormone is presented in the form of hexamers. The molecules of this substance are polymers. Hexamers are slowly absorbed, which does not allow reaching the level of plasma insulin concentration healthy person after eating food.

This circumstance was the beginning of the manufacture of semi-synthetic drugs, which are:

dimers;
monomers.

Numerous clinical trials have been conducted, resulting in the development of the most effective means, the names of the most famous

Aspart insulin;
Lispro-insulin.

These types of insulin are absorbed from under the skin 3 times faster than human insulin. This leads to highest level insulin levels in the blood are reached quickly, and the glucose lowering agent acts more quickly.

With the introduction of a semi-synthetic drug 15 minutes before a meal, the effect will be the same as when insulin is injected for a person 30 minutes before a meal.

Such hormones of too fast influence include lispro-insulin. It is a derivative of human insulin obtained by replacing proline and lysine in places 28 and 29 of the B chain.

As in human insulin, lispro-insulin exists in the form of hexamers in manufactured preparations, but after the agent enters the human body, it turns into monomers.

For this reason, lipo-insulin has quick influence, but the effect lasts a short time. Lipro-insulin wins over other drugs of this type on the following factors:

makes it possible to reduce the threat of hypoglycemia by 20-30%;
is able to reduce the amount of A1c glycosylated hemoglobin, which indicates an effective treatment of diabetes mellitus.

In the formation of aspart-insulin, an important part is given to replacement, when aspartic acid takes the place of Pro28 in the B-chain. As with lispro-insulin, this medical drug, penetrating into human body, soon splits into monomers.

Pharmacokinetic properties of insulin

In diabetes mellitus, the pharmacokinetic properties of insulin may be different. The time of peak plasma insulin levels and the greatest effect of sugar reduction can differ by 50%. Some magnitude of such fluctuations depends on different rates of assimilation medicinal product from the subcutaneous tissue. Still, the time of long and short insulin varies too much.

by the most strong impact hormones of medium duration and long-term influence differ. But more recently, experts have found that short-acting agents have the same properties.

Depending on insulin, it is necessary to regularly inject the hormone into subcutaneous tissue. This also applies to those patients who are not able to reduce the amount of glucose in the plasma due to diet and sugar-lowering drugs, as well as women with diabetes during pregnancy, patients in whom the disease was formed due to pacreatectomy. Here we can say that they do not always give the expected effect.

Insulin treatment is necessary for diseases such as:

hyperosmolar coma;
diabetic ketoacidosis;
after surgery for patients with diabetes,
while insulin treatment contributes to the normalization of the amount of sugar in the plasma,
elimination of other metabolic pathologies.

The best result can be achieved with complex therapy methods:

injections;
physical exercise;
diet.

Daily need for insulin

A person with good health and a normal physique per day produces 18-40 units or 0.2-0.5 units / kg of long-term insulin. About half of this volume is gastric secretion, the rest is excreted after eating food.

The hormone is produced 0.5-1 units per hour. After sugar enters the bloodstream, the rate of hormone secretion rises to 6 units per hour.

People with overweight and the presence of insulin resistance, who do not suffer from diabetes, have 4 times faster insulin production after eating. There is a connection of the hormone formed by the portal system of the liver, where one part is destroyed and does not reach the bloodstream.

In patients with type 1 diabetes, the daily need for the hormone insulin is different:

Basically, this indicator varies from 0.6 to 0.7 units / kg.
With a large weight, the need for insulin increases.
When a person needs only 0.5 units / kg per day, he has sufficient hormone production or excellent physical shape.

The need for the hormone insulin is of 2 types:

post-prandial;
basal.

About half of the daily requirement belongs to the basal type. This hormone is involved in preventing the breakdown of sugar in the liver.

In post-prandial form daily requirement given by injection before meals. The hormone takes part in the absorption of nutrients.

The patient is given an injection of insulin with an average duration of action once a day, or combined remedy, which combines insulin of short duration and a hormone of medium duration. This may not be enough to maintain glycemia at a normal level.

Then a more complex therapy regimen is used, where insulin of medium duration is used in combination with short-acting insulin or long-acting insulin with short-acting insulin.

Often the patient is treated with a mixed therapy regimen where he injects himself with one injection during breakfast and one during dinner. The hormone in this case consists of insulin of short duration and medium duration.

When receiving an evening dose of the NPH hormone or insulin tape, it does not give the necessary level of glycemia at night, then the injection is divided into 2 parts: before dinner, the patient is given a short-term insulin injection, and before going to bed, they put NPH insulin or insulin tape.

Formula, chemical name: there is no data.
Pharmacological group: hormones and their antagonists/insulins.
Pharmachologic effect: hypoglycemic.

Pharmacological properties

Human insulin is an intermediate-acting insulin preparation produced by recombinant DNA technology. Human insulin regulates the concentration of glucose in the blood, the deposition and metabolism of carbohydrates, fats, proteins in target organs (skeletal muscles, liver, adipose tissue). Human insulin has anabolic and anti-catabolic properties. AT muscle tissue there is an increase in the content of glycerol, glycogen, fatty acids, increased protein synthesis and increased consumption of amino acids, but at the same time there is a decrease in gluconeogenesis, lipolysis, glycogenolysis, ketogenesis, protein catabolism and release of amino acids. Human insulin binds to a membrane receptor (a tetramer, which consists of 4 subunits, 2 of which (beta) are embedded in the cytoplasmic membrane and carry tyrosine kinase activity, and the other 2 (alpha) are located extramembrane and are responsible for hormone binding), forms an insulin receptor complex, which undergoes autophosphorylation. This complex in intact cells phosphorylates the threonine and serine ends of protein kinases, which leads to the formation of phosphatidylinositolglycan and triggers phosphorylation, which activates enzymatic activity in target cells. In muscles and other tissues (except the brain) it promotes intracellular transfer of glucose and amino acids, slows down protein catabolism, and stimulates synthetic processes. Human insulin promotes the accumulation of glucose in the liver in the form of glycogen and inhibits glycogenolysis (gluconeogenesis). Individual differences in insulin activity depend on dose, injection site, physical activity patient, diet and other factors.
The absorption of human insulin depends on the method and site of administration (thigh, abdomen, buttocks), insulin concentration, injection volume. Human insulin is distributed unevenly throughout the tissues; does not penetrate into breast milk and across the placental barrier. Degradation of the drug occurs in the liver under the action of insulinase (glutathione-insulin transhydrogenase), which hydrolyzes the disulfide bonds between chains A and B and makes them available to proteolytic enzymes. Human insulin is excreted by the kidneys (30 - 80%).

Indications

Diabetes mellitus type 1 and 2 requiring insulin therapy (in case of resistance to oral hypoglycemic drugs or in case of combined treatment; intercurrent conditions), diabetes mellitus during pregnancy.

Method of application of human insulin and dose

The route of administration of the drug depends on the type of insulin. The dose is set by the doctor individually, depending on the level of glycemia.
Subcutaneous injections are carried out in the area of the anterior abdominal wall, thighs, shoulders, buttocks. Injection sites should be rotated so that the same site is used no more than about once a month. When administering insulin subcutaneously, care must be taken not to get into the blood vessel. Patients must be educated correct use devices for administering insulin. Do not massage the injection site after injection. The temperature of the administered drug should correspond to room temperature.
Reducing the number of daily injections is achieved by combining insulins of different durations of action.
With the development allergic reactions it is necessary to hospitalize the patient, identify the component of the drug that was the allergen, prescribe adequate therapy and insulin replacement.
Discontinuation of therapy or the use of inadequate doses of insulin, especially in patients with type 1 diabetes mellitus, can lead to hyperglycemia and diabetic ketoacidosis (conditions that are potentially life-threatening for the patient).
The development of hypoglycemia when using the drug is promoted by an overdose, physical activity, diet violations, organic kidney damage, and fatty infiltration of the liver.
The dose of insulin should be adjusted if functional state pituitary gland, adrenal glands, thyroid gland, kidney and / or liver, Addison's disease, hypopituitarism, diabetes mellitus in patients over 65 years of age. Also, a change in the dose of insulin may be required when increasing the intensity of physical activity or changing the usual diet. Ethanol intake (including soft drinks) can cause hypoglycemia. Ethanol should not be taken on an empty stomach. For some comorbidities(especially infectious), conditions that are accompanied by fever, emotional overstrain, the need for insulin may increase.
Symptoms of hypoglycemia with human insulin in some patients may be less pronounced or different from those observed in them when using animal insulin. With the normalization of blood glucose, for example, with intensive treatment with insulin, all or some of the symptoms, precursors of hypoglycemia, may disappear, of which patients should be informed. Symptoms of hypoglycemia may become less pronounced or change with long course diabetes mellitus, diabetic neuropathy, the use of beta-blockers.
For some patients, when switching from animal insulin to human insulin, it may be necessary to adjust the dose. This can happen as early as the first injection of a human insulin preparation or gradually over several weeks or months after the transfer.
The transition from one type of insulin to another must be carried out under strict medical supervision and control of blood glucose. Activity change, trademark(manufacturer), type, species (human, animal, human insulin analogs) and/or method of manufacture (DNA recombinant or animal insulin) may result in the need for dose adjustments.
When using insulin preparations simultaneously with drugs of the thiazolidinedione group, the risk of developing edema and chronic heart failure increases, especially in patients with pathology of the circulatory system and the presence of risk factors for chronic heart failure.
With hypoglycemia in a patient, the speed of psychomotor reactions and concentration of attention may decrease. This can be dangerous when these abilities are especially needed (for example, operating mechanisms, driving vehicles, and others). Patients should be advised to take precautions to prevent the development of hypoglycemia when performing potentially dangerous species activities that require rapid psychomotor reactions and heightened attention(including driving vehicles, working with mechanisms). This is especially important for patients with absent or mild symptoms, precursors of hypoglycemia, as well as with the frequent development of hypoglycemia. In such cases, the doctor must assess the appropriateness of the patient to perform such activities.

Contraindications for use

Hypersensitivity, hypoglycemia.

Application restrictions

There is no data.

Use during pregnancy and lactation

During pregnancy, it is especially important to maintain good glycemic control in women who are receiving insulin treatment. During pregnancy and lactation, it is necessary to adjust the dose of insulin to compensate for diabetes. The need for insulin usually decreases in the first trimester of pregnancy and increases in the second and third trimester of pregnancy. The need for insulin can drop dramatically during and immediately after childbirth. Women with diabetes need to inform the doctor about pregnancy or its planning. Women with diabetes may need to adjust their insulin dose and/or diet while breastfeeding. Human insulin was not mutagenic in in vitro and in vivo series in genetic toxicity studies.

Side effects of human insulin

Hypoglycemia (pallor skin, increased sweating, lethargy, tremor, trembling, perspiration, nausea, vomiting, tachycardia, palpitations, hunger, agitation, anxiety, paresthesia in the mouth, headache, drowsiness, insomnia, fear, depressive mood, irritability, unusual behavior, uncertainty movements, confusion, speech and vision disorders, loss of consciousness, coma, death), posthypoglycemic hyperglycemia (Somoji phenomenon), insulin resistance (daily requirement exceeds 200 units), edema, visual impairment, allergic reactions (itching, skin rash, generalized itching, shortness of breath, shortness of breath, dyspnea, excessive sweating, increased heart rate, hypotension, anaphylactic shock), local reactions(swelling, itching, soreness, redness, post-injection lipodystrophy, which is accompanied by impaired insulin absorption, development pain when atmospheric pressure changes).

Interaction of human insulin with other substances

The hypoglycemic effect of human insulin is reduced by glucocorticoids (dexamethasone, betamethasone, hydrocortisone, prednisolone and others), amphetamines, adrenocorticotropic hormone, fludrocortisone, calcium channel blockers, estrogens, baclofen, heparin, levothyroxine sodium, oral contraceptives, thyroid hormones, nicotine, thiazide and others diuretics (hydrochlorothiazide, indapamide and others), amprenavir, danazol, isoniazid, diazoxide, lithium carbonate, chlorprothixene, sympathomimetics, a nicotinic acid, beta-agonists (for example, ritodrine, salbutamol, terbutaline and others), tricyclic antidepressants, epinephrine, glucagon, morphine, clonidine, growth hormone, phenytoin, phenothiazine derivatives. It may be necessary to increase the dose of biphasic [human engineered] insulin when used with these drugs.
The hypoglycemic effect of human insulin is enhanced by metformin, sulfonamides, repaglinide, androgens, oral hypoglycemic drugs, testosterone, anabolic steroids, bromocriptine, disopyramide, guanethidine, monoamine oxidase inhibitors, angiotensin II receptor antagonists, carbonic anhydrase inhibitors, fluoxetine, carvedilol, fenfluramine inhibitors , enalapril and others), tetracyclines, octreotide, mebendazole, ketoconazole, clofibrate, theophylline, quinidine, chloroquine, non-steroidal anti-inflammatory drugs, salicylates, cyclophosphamide, pyridoxine, beta-blockers (betaxolol, metoprolol, pindolol, sotalol, bisoprolol, timolol and others) (mask the symptoms of hypoglycemia, including tachycardia, increased blood pressure), ethanol and ethanol-containing drugs. Dose reduction of biphasic [human engineered] insulin may be required when used with these drugs.
Beta-blockers, clonidine, reserpine can hide the manifestation of symptoms of hypoglycemia.
Against the background of atenolol (unlike non-selective beta-blockers), the effect is slightly enhanced; it is necessary to warn the patient that with the development of hypoglycemia, tachycardia and tremor may be absent, but irritability, hunger, nausea should persist, and sweating even increases.
The concentration of human insulin in the blood is increased (due to the acceleration of absorption) by nicotine-containing drugs and smoking.
Against the background of octreotide, reserpine, a change in the hypoglycemic effect (both strengthening and weakening) is possible, requiring adjustment of the dose of insulin.
Against the background of clarithromycin, the rate of destruction slows down and, in some cases, the effect of insulin may increase.
Against the background of diclofenac, the effect of the drug changes; when used together, blood glucose control is necessary.
Against the background of metoclopramide, which accelerates gastric emptying, it may be necessary to change the doses or regimen of insulin administration.
Human insulin is pharmaceutically incompatible with solutions of other drugs.
If necessary, use other medicines in addition to human insulin, you should consult your doctor.

Overdose

With an overdose of human insulin, hypoglycemia develops (lethargy, increased sweating, pallor of the skin, palpitations, tachycardia, hunger, tremor, trembling, perspiration, nausea, vomiting, paresthesia in the mouth, drowsiness, headache, anxiety, agitation, insomnia, fear , irritability, unsteady movements, depressive mood, unusual behavior, confusion, speech and vision disturbances, loss of consciousness) varying degrees severity, up to hypoglycemic coma and lethal outcome. Under certain conditions, for example, with a long duration or with intensive control of diabetes, the symptoms of hypoglycemia may change.
Treatment: mild hypoglycemia can be controlled by oral glucose, sugar, foods that are rich in carbohydrates, insulin dose adjustment, physical activity or diet may be required; with moderate hypoglycemia, intramuscular or subcutaneous administration of glucagon is necessary, with further ingestion of carbohydrates; at severe conditions hypoglycemia associated with neurological disorders, convulsions, coma, requires intramuscular or subcutaneous administration of glucagon or / intravenous administration concentrated 40% dextrose (glucose) solution, after regaining consciousness, the patient must be given food that is rich in carbohydrates to prevent the recurrence of hypoglycemia. Further intake of carbohydrates and monitoring of the patient may be required, since relapse of hypoglycemia is possible.

The human pancreas, due to various reasons, often cannot produce insulin. Then you need to use genetically engineered insulin, which replaces human insulin.

The human form of insulin is obtained either from the synthesis of Escherichia coli, or from porcine insulin by replacing one amino acid.

To imitate normal work human pancreas, produce insulin injections. The type of insulin is chosen based on the type of disease and the patient's well-being. Insulin can be administered intravenously or intramuscularly. For lifelong and long-term therapy, subcutaneous injections are most often used.

Features of insulin

Insulin-dependent diabetes mellitus requires lifelong treatment. Human life depends on the availability of insulin. The disease is recognized as a non-communicable epidemic and ranks third in terms of distribution in the world.

Insulin was first created from the pancreas of a dog. A year later, the drug was introduced into widespread use. After 40 years, it became possible to synthesize the hormone chemically.

After some time, types of insulin with a high degree of purification were invented. Work is also underway to synthesize human insulin. Since 1983, this hormone began to be produced on an industrial scale.

Previously, diabetes was treated with drugs created from animals. These drugs are now banned. In pharmacies, only genetic engineering products can be purchased; the creation of these drugs is based on the transplantation of a gene product into a cell of a microorganism.

For these purposes, yeast or a non-pathogenic type of E. coli bacteria are used. As a result, microorganisms begin to produce the hormone insulin for humans.

The modern insulin preparation is different:

time of exposure, there are short-acting, ultra-short-acting and long-acting insulins,
amino acid sequence.

There are also combined preparations, which are called "mixes". These drugs include long-acting and short-acting insulin.

Receiving insulin may be indicated for diagnoses such as:

Lactic acid, diabetic and hypermolar coma,
Insulin type 1 diabetes mellitus,
For infections, surgical interventions exacerbations of chronic diseases,
Diabetic nephropathy and / or abnormal liver function, pregnancy and childbirth,
Non-insulin dependent type 2 diabetes mellitus with resistance to antidiabetic oral agents,
Dystrophic skin lesions
Severe asthenization in various pathologies,
Prolonged infectious process.

Duration of insulin action

Sugar level

According to the duration and mechanism of action, insulins are distinguished:

ultrashort,
short,
average duration,
prolonged action.

Ultrashort insulins act immediately after injection. Maximum effect reached in an hour and a half.

The duration of action reaches 4 hours. This type of insulin can be administered either before a meal or immediately after a meal. Receiving this insulin does not require pauses between injection and meals.

Ultrashort insulin does not require additional use food at the peak of action, which is more convenient compared to other types. These insulins include:

Apidra,
Humalog.

Short insulins begin to act after half an hour. The peak of action begins after 3 hours. The action lasts approximately 5 hours. This type of insulin is administered before meals, you need to pause between the injection and the meal. Eating is allowed after 15 minutes.

Using short-acting insulin, you need to have a snack a few hours after the injection. The time of eating should coincide with the time of peak action of the hormone. Short insulins are:

Himulin Regular,
Actrapid,
Monodar (K50, K30, K15),
Insuman Rapid,
Humodar and others.

Intermediate-duration insulins are drugs that last 12-16 hours. In type 1 diabetes, human insulin is used as background or basal insulin. Sometimes you need to do injections 2 or 3 times a day in the morning and evening time with a break of 12 hours.

Such insulin begins to work after 1-3 hours, reaching a peak after 4-8 hours. Duration is 12-16 hours. Intermediate drugs include:

Humodar br,
Protafan,
Humulin NPH,
Novomix.
Insuman Bazal.

Long-acting insulins are background or basal insulin. A person may need one or two injections per day. They are used in the treatment of type 2 diabetes.

The drugs have a cumulative effect. The effect of the dosage is maximally manifested after 2-3 days. Long-acting insulins work 4-6 hours after injection. Their peak of action occurs in 11-14 hours, the action itself lasts about a day.

Among these drugs there are insulins that do not have a peak of action. Such funds act gently and for the most part imitate the effect natural hormone in a healthy person.

These insulins include:

lantus,
Monodar Long,
Monodar ultralong,
ultralente,
ultralong,
Humulin L and others,
lantus,
Levemir.

Side effects and dosage violations

With an overdose of insulin preparations, a person may experience:

Weakness,
Cold sweat,
Pallor,
Shiver,
frequent heartbeat,
Headache,
Hunger,
Seizures.

All of the above are considered symptoms of hypoglycemia. If the condition has just begun to form and is in the early stages, you can remove the symptoms yourself. For these purposes, take products with sugar and large quantity easily digestible carbohydrates.

You can also inject a solution of dextrose and glucagon into the body. If the patient has fallen into a coma, a modified dextrose solution should be administered. It is used until the condition improves.

Some patients may develop allergies to insulin. Among the main symptoms:

Prostration,
puffiness,
Hives,
Rash,
Fever,
Decreased blood pressure.

Hyperglycemia occurs due to low dosages or with the development infectious disease, as well as non-compliance with the diet. Sometimes a person develops lipodystrophy where the drug is injected.

When using the drug may also occur on a temporary basis:

puffiness,
Drowsiness,
Loss of appetite.

Getting a hormone replacement instead of human insulin is excellent remedy in the treatment of diabetes mellitus. The substance helps to reduce the level of glucose in the blood, due to the fact that glucose is better absorbed by cells, the process of its transportation changes. These drugs replace human insulin, but should only be taken as directed by a doctor as they may negative consequences for good health.

Important instructions for use

Women with diabetes should inform their doctor about planning or pregnancy. This category of women often requires a change in dosage during lactation, as well as dietary nutrition.

Investigating the toxicity of insulin preparations, scientists have not found a mutagenic effect.

It is worth noting that the need for the hormone may decrease if a person has kidney failure. Switching a person to a different type of insulin or to a drug with a different brand name is possible only under close medical supervision.

The dosage must be adjusted if the activity of insulin, its type or species is changed. The need for insulin may decrease with the following diseases:

Insufficient function of the adrenal glands, thyroid gland or pituitary gland,
Liver and kidney failure.

With emotional stress or certain diseases, the need for insulin increases. A change in dosage is also required with increased physical activity.

Symptoms of hypoglycemia, if human insulin is administered, may be less pronounced, or different from that which was with the introduction of insulin of animal origin.

When blood sugar levels are normalized, for example, as a result of intensive treatment with insulin, all or some of the manifestations of hypoglycemia may disappear, of which people should be informed.

Harbingers of hypoglycemia may change or be mild with long-term treatment diabetes or when using beta-blockers.

A local allergic reaction may be caused by causes that are not related to the action of the drug, such as skin irritation chemicals or improper injection.

In some cases, the formation of a permanent allergic reaction requires immediate therapy. Desensitization or an insulin change may also be required.

With hypoglycemia in a person, the concentration of attention and the speed of the psychomotor reaction may decrease. This can be dangerous in cases where these functions are vital. An example is driving a car or various mechanisms.

This is extremely important for people who have unexpressed symptoms that are a harbinger of hypoglycemia. In these cases, the attending physician needs to assess the need for autodriving by the patient. The video in this article will talk about the types of insulin.

Sugar level

Recent discussions.

Insulin is the main drug for the treatment of people with type 1 diabetes. Sometimes it is also used to stabilize the patient's condition and improve his well-being in the second type of disease. This substance, by its nature, is a hormone that is capable of influencing the metabolism of carbohydrates in small doses. Normally, the pancreas produces enough insulin, which helps maintain normal blood sugar levels. But with serious endocrine disorders Injections of insulin often become the only chance to help the patient. Unfortunately, it is impossible to take it orally (in the form of tablets), since it is completely destroyed in digestive tract and loses its biological value.

Options for obtaining insulin for use in medical practice

Many diabetics must have at least once wondered what insulin is used for, which is used in medical purposes? Currently, most often this medicine is obtained using methods genetic engineering and biotechnology, but sometimes it is extracted from raw materials of animal origin.

Preparations derived from raw materials of animal origin

Obtaining this hormone from the pancreas of pigs and large cattle- an old technology that is rarely used today. This is due to the low quality of the drug received, its tendency to cause allergic reactions and insufficient degree cleaning. The fact is that, since the hormone is a protein substance, it consists of a certain set of amino acids.

The insulin produced in the body of a pig differs in amino acid composition from human insulin by 1 amino acid, and bovine insulin by 3.

At the beginning and middle of the 20th century, when similar drugs did not exist, even such insulin became a breakthrough in medicine and made it possible to bring the treatment of diabetics to new level. Hormones obtained by this method lowered blood sugar, although they often caused side effects and allergies. Differences in the composition of amino acids and impurities in the drug affected the condition of patients, especially in more vulnerable categories of patients (children and the elderly). Another reason poor tolerance of such insulin is the presence of its inactive precursor in the drug (proinsulin), which was impossible to get rid of in this variation of the drug.

Nowadays, there are improved porcine insulins that are devoid of these shortcomings. They are obtained from the pancreas of a pig, but after that they are subject to additional processing and purification. They are multicomponent and contain excipients in their composition.

Modified porcine insulin is practically no different from the human hormone, so it is still used in practice.

Such drugs are much better tolerated by patients and practically do not cause adverse reactions, they do not suppress the immune system and effectively reduce blood sugar. Bovine insulin is not used in medicine today, because due to its foreign structure, it negatively affects the immune and other systems of the human body.

Genetically engineered insulin

Human insulin, which is used for diabetics, is produced on an industrial scale in two ways:

using enzymatic treatment of porcine insulin;
using genetically modified strains of Escherichia coli or yeast.

With a physicochemical change, the porcine insulin molecules under the action of special enzymes become identical to human insulin. The amino acid composition of the resulting drug is no different from the composition of the natural hormone that is produced in the human body. During the production process, the medicine undergoes high purification, therefore it does not cause allergic reactions and other undesirable manifestations.

But most often, insulin is obtained using modified (genetically modified) microorganisms. Bacteria or yeast are biotechnologically altered so that they can produce insulin themselves.

In addition to receiving insulin itself, important role plays his cleaning. So that the drug does not cause any allergic and inflammatory reactions, at each stage it is necessary to monitor the purity of strains of microorganisms and all solutions, as well as the ingredients used.

There are 2 methods for obtaining insulin in this way. The first of them is based on the use of two different strains (species) of a single microorganism. Each of them synthesizes only one strand of the hormone DNA molecule (there are two in total, and they are spirally twisted together). Then these chains are connected, and in the resulting solution it is already possible to separate active forms insulin from those that have no biological significance.

The second way to obtain a drug using E. coli or yeast is based on the fact that the microbe first produces inactive insulin (that is, its precursor, proinsulin). Then, with the help of enzymatic treatment, this form is activated and used in medicine.

Personnel who have access to certain production areas must always be dressed in a sterile protective suit, so that the contact of the drug with biological fluids human is excluded

All these processes are usually automated, air and all contact surfaces with ampoules and vials are sterile, and lines with equipment are hermetically sealed.

Biotechnology methods enable scientists to think about alternative solutions to the problem of diabetes. For example, preclinical studies are currently underway to produce artificial pancreatic beta cells, which can be obtained using genetic engineering methods. Perhaps in the future they will be used to improve the functioning of this organ in a sick person.

Modern production is complex technological process, which provides for automation and minimal human intervention

Additional components

Manufacture of insulin excipients in modern world almost impossible to imagine, because they improve its chemical properties, extend the duration of action and achieve a high degree of purity.

According to their properties, all additional ingredients can be divided into the following classes:

prolongators (substances that are used to ensure a longer action of the drug);
disinfectant components;
stabilizers, thanks to which optimal acidity is maintained in the drug solution.

Prolonging additives

There are extended-acting insulins, the biological activity of which lasts for 8 to 42 hours (depending on the drug group). This effect is achieved by adding injection solution special substances - prolongators. Most often, one of the following compounds is used for this purpose:

proteins;
chloride salts of zinc.

Proteins that prolong the action of the drug are highly purified and are low allergenic (for example, protamine). Zinc salts also do not negative influence neither on the activity of insulin, nor on the well-being of a person.

Antimicrobial Ingredients

Disinfectors in the composition of insulin are necessary so that the microbial flora does not multiply during storage and use. These substances are preservatives and ensure the safety of the biological activity of the drug. In addition, if a patient injects a hormone from one vial only to himself, then the medicine may last him for several days. Due to high-quality antibacterial components, he will not need to throw away an unused drug due to the theoretical possibility of reproduction in a solution of microbes.

The following substances can be used as disinfectants in the production of insulin:

metacresol;
phenol;
parabens.

If the solution contains zinc ions, they also act as an additional preservative due to their antimicrobial properties.

For the production of each type of insulin, certain disinfectant components are suitable. Their interaction with the hormone must be investigated at the stage of preclinical trials, since the preservative should not disrupt the biological activity of insulin or otherwise adversely affect its properties.

The use of preservatives in most cases allows you to enter the hormone under the skin without pre-treatment with alcohol or other antiseptics (the manufacturer usually mentions this in the instructions). This simplifies the administration of the drug and reduces the number of preparatory manipulations before the injection itself. But this recommendation works only when the solution is administered using an individual insulin syringe with a thin needle.

Stabilizers

Stabilizers are needed to keep the pH of the solution at a given level. The level of acidity depends on the safety of the drug, its activity and stability. chemical properties. In the production of injectable hormone for diabetic patients, phosphates are usually used for this purpose.

Solution stabilizers are not always needed for insulins with zinc, since the metal ions help maintain the necessary balance. If they are still used, then other chemical compounds are used instead of phosphates, since the combination of these substances leads to precipitation and the unsuitability of the drug. Important property, presented to all stabilizers - safety and the inability to enter into any reactions with insulin.

The selection of injectable drugs for diabetes for each individual patient should be handled by a competent endocrinologist. The task of insulin is not only to maintain normal level blood sugar, but also not harm other organs and systems. The drug should be chemically neutral, low allergenic and preferably affordable. It is also quite convenient if the selected insulin can be mixed with other versions of it for the duration of action.

Insulin is vital drug, he has made a real revolution in the lives of many people with diabetes.

In the entire history of medicine and pharmacy of the 20th century, perhaps only one group of medicines of the same importance can be distinguished - these are antibiotics. They, like insulin, very quickly entered medicine and helped save many lives.

The Day of the fight against diabetes is celebrated at the initiative of the World Health Organization every year since 1991 on the birthday of the Canadian physiologist F. Banting, who discovered the hormone insulin together with J. J. Macleod. Let's take a look at how this hormone is made.

How do insulin preparations differ from each other?

The degree of purification.
The source of receipt is porcine, bovine, human insulin.
Additional components included in the solution of the drug - preservatives, prolongers of action and others.
Concentration.
solution pH.
Possibility of mixing short and long-acting preparations.

Insulin is a hormone produced by special cells in the pancreas. It is a double-stranded protein with 51 amino acids.

About 6 billion units of insulin are used annually in the world (1 unit is 42 micrograms of a substance). The production of insulin is high-tech and is carried out only by industrial methods.

Sources of insulin

Currently, depending on the source of production, porcine insulin and human insulin preparations are isolated.

Pork insulin now has a very a high degree cleaning, has a good hypoglycemic effect, there are practically no allergic reactions to it.

Human insulin preparations fully comply with chemical structure human hormone. They are usually produced by biosynthesis using genetic engineering technologies.

Large manufacturing firms use such production methods that guarantee that their products meet all quality standards. Big differences in the action of human and porcine monocomponent insulin (that is, highly purified) have not been identified, in relation to immune system, according to many studies, the difference is minimal.

Auxiliary components used in the production of insulin

The drug vial contains a solution containing not only the hormone insulin itself, but also other compounds. Each of them plays a specific role:

prolongation of the action of the drug;
solution disinfection;
the presence of buffer properties of the solution and maintaining a neutral pH (acid-base balance).

Extending the action of insulin

To create long-acting insulin, one of two compounds, zinc or protamine, is added to a solution of regular insulin. Depending on this, all insulins can be divided into two groups:

protamine-insulins - protafan, insuman basal, NPH, humulin N;
zinc-insulins - insulin-zinc-suspensions mono-tard, tape, humulin-zinc.

Protamine is a protein, but adverse reactions in the form of an allergy to it are very rare.

To create a neutral environment for the solution, a phosphate buffer is added to it. It must be remembered that insulin containing phosphates is strictly forbidden to combine with insulin-zinc suspension (ICS), since zinc phosphate precipitates, and the effect of zinc-insulin is shortened in the most unpredictable way.

Disinfectants

Some of the compounds that, according to pharmaco-technological criteria, should already be introduced into the preparation have a disinfecting effect. These include cresol and phenol (both of which have a specific odor), as well as methyl parabenzoate (methylparaben), which has no odor.

The introduction of any of these preservatives causes the specific smell of some insulin preparations. All preservatives in the amount in which they are in insulin preparations do not have any negative effect.

Protamine insulins usually include cresol or phenol. Phenol cannot be added to ICS solutions, because it changes physical properties hormone particles. These drugs include methylparaben. Zinc ions in solution also have an antimicrobial effect.

Thanks to this multi-stage antibacterial protection with the help of preservatives, the development of possible complications is prevented, which could be caused by bacterial contamination when the needle is repeatedly inserted into the vial with the solution.

Due to the presence of such a protection mechanism, the patient can use for subcutaneous injection the same syringe for 5 to 7 days (provided that only he uses the syringe). Moreover, preservatives make it possible not to use alcohol to treat the skin before injection, but again only if the patient injects himself with a syringe with a thin needle (insulin).

Calibration of insulin syringes

In the first preparations of insulin, one ml of the solution contained only one unit of the hormone. Later the concentration was increased. Most of insulin preparations in vials used in Russia, contains 40 units in 1 ml of solution. The vials are usually marked with the symbol U-40 or 40 units / ml.

They are intended for wide use just for such insulin and their calibration is made according to following principle: when typing 0.5 ml of a solution with a syringe, a person gains 20 units, 0.35 ml corresponds to 10 units, and so on.

Each mark on the syringe is equal to a certain volume, and the patient already knows how many units this volume contains. Thus, the calibration of syringes is a graduation in terms of the volume of the drug, calculated on the use of U-40 insulin. 4 units of insulin are contained in 0.1 ml, 6 units in 0.15 ml of the drug, and so on up to 40 units, which correspond to 1 ml of solution.

In some countries, insulin is used, 1 ml of which contains 100 units (U-100). For such drugs, special insulin syringes are produced that are similar to those discussed above, but they have a different calibration.

It takes into account exactly this concentration (it is 2.5 times higher than the standard one). In this case, the dose of insulin for the patient, of course, remains the same, since it satisfies the body's need for a specific amount of insulin.

That is, if the patient previously used the U-40 preparation and injected 40 units of the hormone per day, then he should receive the same 40 units with injections of U-100 insulin, but inject it in an amount 2.5 times less. That is, the same 40 units will be contained in 0.4 ml of the solution.

Unfortunately, not all doctors, let alone diabetic patients, know about this. The first difficulties began when some of the patients switched to the use of insulin injectors (pen-syringes), which use penfills (special cartridges) containing U-40 insulin.

If you draw a solution labeled U-100 into such a syringe, for example, up to the mark of 20 units (that is, 0.5 ml), then this volume will contain as many as 50 units of the drug.

Every time you fill up with U-100 insulin conventional syringes and while looking at the cut-off units, a person will gain a dose 2.5 times greater than that shown at the level of this mark. If neither the doctor nor the patient notices this error in a timely manner, then there is a high probability of developing severe hypoglycemia due to a constant overdose of the drug, which often happens in practice.

On the other hand, sometimes there are insulin syringes calibrated specifically for the U-100 preparation. If such a syringe is mistakenly filled with the usual U-40 solution, then the dose of insulin in the syringe will be 2.5 times less than that written near the corresponding mark on the syringe.

As a result of this, a seemingly inexplicable increase in blood glucose is possible. In fact, of course, everything is quite logical - for each concentration of the drug, you must use a suitable syringe.

In some countries, such as Switzerland, there has been an elaborate plan to make a smart transition to U-100-labeled insulin preparations. But this requires close contact of all stakeholders: doctors of many specialties, patients, nurses from any department, pharmacists, manufacturers, authorities.

In our country, it is very difficult to implement the transition of all patients to only the use of U-100 insulin, because, most likely, this will lead to an increase in the number of errors in dose determination.

Combined use of short-acting and extended-acting insulins

AT modern medicine treatment of diabetes mellitus, especially type 1, usually occurs using a combination of two types of insulin - short-acting and long-acting.

It would be much more convenient for patients if drugs with different duration actions could be combined in one syringe and injected simultaneously to avoid double skin puncture.

Many doctors do not know what determines the possibility of mixing different insulins. This is based on the chemical and galenic (compositionally determined) compatibility of long-acting and short-acting insulins.

It is very important that when the two types of preparations are mixed, the rapid onset of action of short-acting insulin does not stretch or disappear.

It has been proven that a short-acting preparation can be combined in one injection with protamine-insulin, while the onset of short-acting insulin is not delayed, because soluble insulin does not bind to protamine.

In this case, the manufacturer of the drug does not matter. For example, it can be combined with humulin H or protafan. Moreover, mixtures of these preparations can be stored.

With regard to zinc-insulin preparations, it has long been established that insulin-zinc suspension (crystalline) cannot be combined with short insulin, as it binds to an excess of zinc ions and transforms into prolonged insulin, sometimes partially.

Some patients first inject a short-acting drug, then, without removing the needle from under the skin, slightly change its direction, and inject zinc-insulin through it.

Very little scientific research has been conducted on this method of administration, so it cannot be ruled out that in some cases, with this method of injection, a complex of zinc-insulin and a short-acting preparation can form under the skin, which leads to a violation of the absorption of the latter.

Therefore, it is better to administer short insulin completely separately from zinc insulin, to make two separate injections into skin areas that are at least 1 cm apart from each other. This is not convenient, which cannot be said about the standard intake.

Combined insulins

Now the pharmaceutical industry produces combined preparations containing short-acting insulin together with protamine-insulin in a strictly defined percentage. These drugs include:

mixtard,
actrafan,
insuman comb.

The most effective are combinations in which the ratio of short and extended insulin is 30:70 or 25:75. This ratio is always indicated in the instructions for use of each specific drug.

Such drugs are best suited for people who observe constant mode nutrition with regular physical activity. For example, they are often used by elderly patients with type 2 diabetes.

Combination insulins are not suitable for so-called "flexible" insulin therapy, when it becomes necessary to constantly change the dosage of short-acting insulin.

For example, this should be done when changing the amount of carbohydrates in food, reducing or increasing physical activity, etc. At the same time, the dose of basal insulin (prolonged) remains practically unchanged.