UA77794U - Combined drug - Google Patents

Abstract

A combined drug containing non-steroid anti-inflammatory agent Ketorolac tromethamine and spasmolytics Pitofenone hydrochloride and Fenpiverinium bromide in pharmaceutically acceptable combination and the excipients is proposed as the analgesic.

Description

The useful model belongs to medicine and pharmacy, in particular to the use of a combined drug that is used as a pain reliever.

Pain is a feeling known to almost everyone. This is confirmed by the fact that many people periodically use various painkillers. Pain has social consequences both for the people who suffer from it and often for those who care for them. Therefore, it is clear that people were constantly looking for ways and means to relieve pain.

Acute and chronic pain should be considered as the most urgent health care problem.

Many people suffer from chronic pain, from pain that is related to trauma, from pain that is caused by surgery, and many patients experience uncontrolled postoperative pain. Pain is a subjective feeling that is often difficult for the patient to describe. The problem is further complicated by the wide individual variability of sensations. Even in the same patient, the reaction to a painful stimulus can be in a wide range depending on the situation. The meaning a patient places on pain can significantly affect the degree of suffering and suffering it causes.

Medicines that can reduce pain have long been well known in medicine.

These agents suppress pain sensitivity without significantly affecting other types of sensitivity and without disturbing consciousness and are called analgesics (from the Latin ap - denial, aYidov5 - pain).

A well-known representative of the group of painkillers is the alkaloid morphine. Other drugs of this group, similar in structure and effect on the human body, were synthesized and used as painkillers.

But when using drugs such as morphine, nausea occurs, up to vomiting, difficulty breathing (up to apnea and asphyxia), slowing of the heart up to its stop, which significantly limits their use in medicine. This especially applies to another representative of the class of narcotic analgesics - fentanyl, when using which side reactions are noted most often, which requires constant monitoring by specialists. In this regard, the use of fentanyl is limited - it is mainly used in inpatient medical institutions.

Unfortunately, to date, not a single drug of this series has been created, which would be in a dose sufficient for

From the development of the therapeutic effect, it would not cause side effects, most often associated with a violation of the functions of the central nervous system (CNS). It is the narcotic analgesics that affect opiate receptors that are used to obtain mental satisfaction. The catastrophic growth of drug addiction and toxic addiction, which is almost epidemic in nature, is drawing attention all over the world. A constant increase in the consumption of narcotic drugs is noted primarily among young people and teenagers. Therefore, these drugs, in addition to medical ones, also have a significant number of social or legislative restrictions for wide, including outpatient, use.

Pyrazolone derivatives widely used in medical practice (analgin - metamizol, baralgin, tempalgin, pentalgin and other agents of the metamizol series) mostly have side effects, a fairly high level of toxicity and negatively affect hematopoietic processes up to agranulocytosis, which is why the use of these analgesics were banned or restricted in 39 countries of the world.

Combined drugs that have an analgesic effect are known in medicine.

A well-known drug is a combination of metamizole, a non-narcotic analgesic of the pyrazolone series, in combination with antispasmodics of myotropic and cholinergic action, pitophenone and fenpiverinium (baralgetas, bral, maxigan, etc.) (1). The drug is used for spastic pain of weak intensity. Disadvantages of this combination are: moderate analgesic activity of metamizole (can be used only for 1 degree of pain treatment), high allergenicity of metamizole, pronounced suppressive effect of metamizole on hematopoiesis, due to which it is prohibited in a number of countries.

A well-known drug is a combination of the non-narcotic analgesic paracetamol with the antispasmodic dicyclomine (cyclopar, combispasm, spazmo, etc.) (2). The drug is used for spastic pain of weak intensity. The disadvantage of such a combination is the moderate analgesic activity of paracetamol (like other non-steroidal anti-inflammatory drugs, it can be used only in the first degree of pain syndrome).

A well-known medicinal product containing the opiatergic analgesic tramadol and the antispasmodic myotropic drotaverine (ША 81269 С2). The drug is used to eliminate pain syndrome of medium intensity. The disadvantage of such a drug is the small analgesic activity of tramadol, which rarely allows to achieve the desired therapeutic effect.

In medical practice, ketorolac is widely used to eliminate pain symptoms as one of the most effective analgesics of the group of nonsteroidal anti-inflammatory drugs (NP33). When administered intramuscularly, 30 mg of the drug has an effect that is comparable to the effect of 10-12 mg of morphine or 50 mg of meperidine. The advantage of ketorolac, compared to narcotic analgesics, is the lack of influence on respiratory, sedative and psychomotor functions. Thus, for postoperative pain, ketorolac was in some cases even more effective than morphine and meperidine, and side effects such as nausea and vomiting were less frequent. Also, ketorolac when administered intramuscularly is comparable in effectiveness to codeine, but it less often causes dyspepsia.

Ketorolac is a non-steroidal anti-inflammatory agent, cyclooxygenase inhibitor, a derivative of the pyrrole-pyrrole group, used in the form of tromethamine salt.

A well-known combined pain reliever. Its composition includes orphenadrine and at least one non-steroidal anti-inflammatory drug represented by ketorolac, diclofenac or naproxen in the form of a pharmaceutically acceptable salt (ША 56366 |).

The drug is intended for the elimination or relief of pain sensations of arbitrary etiology.

It is a known combined analgesic and antispasmodic agent containing analgin (metamizole sodium) as an active ingredient and additionally containing drotaverine (KI 2183116 C2).

The drug is used for the treatment of spastic pain in the form of injections.

This composition has significant disadvantages, because analgin has toxic properties and a high side effect.

The basis of a useful model is the task of developing a new combination of drugs to eliminate the pain syndrome, to develop a drug with a wide spectrum of pharmacological action that will allow optimizing treatment and/or reducing the costs of its implementation.

The solution to the problem is provided by a combined medicinal product containing a non-steroidal anti-inflammatory agent with a pronounced analgesic effect of ketorolac tromethamine and antispasmodic agents pitophenone hydrochloride and fenpiverine bromide in a pharmaceutically acceptable combination and auxiliary substances to reduce side effects.

The proposed combined medicinal product may be intended for elimination

Relief or relief of pain of arbitrary etiology. The proposed drug can be used for acute or chronic pain, in particular, joint syndrome (active phase of rheumatism, rheumatoid arthritis, arthropathy, osteoarthritis, osteochondrosis, spondyloarthrosis, ankylosing spondylitis, Bechterev's disease, gout), lumbago, neuralgia, myalgia, pain from traumatic injury of tissues and musculoskeletal system, pain syndrome and inflammation after surgical interventions, headache with migraine, algodysmenorrhea, pain syndrome with adnexitis, proctitis, colic (biliary and renal), smooth muscle spasms associated with diseases of the biliary system: cholelithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis, spasms of the smooth muscles of the urinary tract: nephrolithiasis, urethrolithiasis, pyelitis, cystitis, bladder tenesmus.

To improve the results of treatment of acute and chronic pain, a combination of painkillers with complementary mechanisms is used. The main goal of this approach is to provide a stronger analgesic activity, in comparison with each of the 3 components of the combination, to reduce the dose of drugs, to improve the time characteristics of the effect. Optimal drug combinations improve the risk/benefit ratio by reducing the side effects of individual components. Recently, in the world pharmaceutical practice, there is a tendency to create ready-made combinations of medicines.

Combinations of painkillers are made taking into account the pharmacological properties of individual components.

Ketorolac is a drug, a non-steroidal anti-inflammatory drug from the acetic acid group, structurally similar to indomethacin.

Ketorolac has the following formula (c) (c)

M

Ketorolac acts on the cyclooxygenase pathway of arachidonic acid metabolism. It suppresses the biosynthesis of prostaglandins, mediators of pain and inflammation, inhibits platelet aggregation, has weak anticholinergic and α-adrenoblocking activity. It has pronounced antinociceptive activity, which is equal to the analgesic activity of opioid analgesics. Ketorolac is used in the treatment of moderate and severe pain syndrome, especially in the postoperative period.

Pitofenone hydrochloride has a direct myotropic effect on smooth muscles.

Fenpiverine bromide has an m-cholinoblocking effect and has an additional myotropic effect on smooth muscles.

Pitofenone hydrochloride and fenpiverine bromide are myotropic antispasmodics that have a direct effect on the smooth muscles of internal organs and cause their relaxation.

The purpose of the claimed utility model is to create a pharmaceutical preparation that is a combination of active ingredients that would potentially exhibit good analgesic properties while minimizing side effects. The above-mentioned task was achieved by the inventors as a result of the combination of a medicinal product with a strongly pronounced analgesic effect of ketorolac tromethamine and antispasmodic agents, which are pitophenone hydrochloride and fenpiverine bromide in a pharmaceutically acceptable combination

The combination of ketorolac tromethamine with pitophenone hydrochloride and fenpiverine bromide has advantages in terms of enhancing its pharmacodynamic effects in the treatment of pain.

The found pharmaceutical composition for the treatment of acute and chronic pain has a simultaneous analgesic, anti-inflammatory and antispasmodic effect and contains active substances, where a therapeutically effective amount of ketorolac tromethamine and a therapeutically effective amount of pitophenone hydrochloride and fenpiverine bromide, as well as auxiliary substances, are used as active substances.

As used herein, the term "therapeutically effective amount" refers to an amount of an active compound or pharmaceutical agent that produces a biological or medical response in a tissue system, animal, or human that is expected by a researcher, veterinarian, medical practitioner, or other clinician, which includes attenuation symptoms of a treatable disease or disorder.

As used herein, the term "therapeutically effective ratio" refers to a quantitative ratio of active compounds or pharmaceutical agents that produces a biological or medical response in a tissue system, animal, or human that is expected by an investigator, veterinarian, medical practitioner, or other clinician that involves alleviating the symptoms of a treatable disease or disorder.

The combined medicinal product may exist as a tablet and/or solution containing ketorolac tromethamine and pitophenone hydrochloride and fenpiverine bromide in any therapeutically effective ratio.

The composition of the combined medicinal product includes excipients.

In the case when the drug is made in the form of a solution, auxiliary substances are sodium chloride, propylene glycol, ethyl alcohol, disodium edetate, sodium hydroxide, water for injections.

When the drug is made in the form of a solid dosage form, in particular in the form of tablets, auxiliary substances are microcrystalline cellulose, crospovidone, starch (potato or corn or pregelatinized or partially pregelatinized), magnesium or calcium stearate. The tablet may also contain additional auxiliary substances, such as croscarmellose sodium, colloidal silicon dioxide, lactose monohydrate, povidone. In addition, the tablet may have a shell containing hydroxypropylmethylcellulose, partially hydrolyzed polyvinyl alcohol, titanium dioxide, macrogol, triacetin, talc, lactose, dyes.

The combined medicinal product can be made in the form of a solid dosage form, in particular in the form of tablets. One tablet may contain 10 mg of ketorolac in the form of tromethamine salt, 10 mg of pitofenone hydrochloride and 0.1 mg of fenpiverine bromide.

Also, the combined drug can be made in the form of a solution, which includes 30 mg of ketorolac in the form of tromethamine salt, 10 mg of pitophenone hydrochloride and 0.1 mg of fenpiverine bromide.

The information that confirms the possibility of implementing the claimed drug is given below.

A combined drug that exists in the form of a solution.

Example 1

One ampoule (2 ml) of the solution contains: ketorolac tromethamine 30 mg pitophenone hydrochloride 10 mg fenpiverine bromide 0.1 mg

Excipients: sodium chloride 0.43-0.75 95 propylene glycol 10-40 95 disodium edetate 0.02-0.05 95 water for injections the rest.

Example 2

One ampoule (2 ml) of the solution contains: ketorolac tromethamine 30 mg pitophenone hydrochloride 10 mg fenpiverine bromide 0.1 mg

Excipients: sodium chloride 0.43-0.75 95 ethyl alcohol 5-40 95 disodium edetate 0.02-0.05 95 water for injections the rest.

Example C

One ampoule (2 ml) of the solution contains: ketorolac tromethamine 30 mg pitophenone hydrochloride 10 mg fenpiverine bromide 0.1 mg

Excipients: sodium chloride 0.43-0.75 95 propylene glycol 10-40 95 ethyl alcohol 5-40 95 disodium edetate 0.02-0.05 95 water for injections the rest.

Example 4

One ampoule (2 ml) of the solution contains: ketorolac tromethamine 30 mg pitophenone hydrochloride 10 mg fenpiverine bromide 0.1 mg

Excipients: sodium chloride 0.43-0.75 95 propylene glycol 10-40 95 disodium edetate 0.02-0.05 95 sodium hydroxide to pH from 6.0 to 7.5 water for injections the rest.

Example 5

One ampoule (2 ml) of the solution contains: ketorolac tromethamine 30 mg pitophenone hydrochloride 10 mg fenpiverine bromide 0.1 mg

Excipients: sodium chloride 0.43 - 0.75 95 propylene glycol 10 - 40 95 ethyl alcohol 5-40 96 disodium edetate 0.02 - 0.05 95 sodium hydroxide to pH from 6.0 to 7.5 water for other the rest of the shares.

Combined drug in the form of a tablet.

One tablet of the combined drug contains active substances in the following amount: ketorolac tromethamine 10 mg pitophenone hydrochloride 10 mg fenpiverine bromide 0.1 mg.

The tablet also contains as auxiliary substances: microcrystalline cellulose up to 70 95 crospovidone up to 10 95 starch (potato or up to 20 95 corn, or pregelatinized, or partially pregelatinized) magnesium or calcium stearate 0.5-1 Fo.

Also, the tablet may contain croscarmellose sodium up to 10 95, colloidal silicon dioxide up to 10 95, lactose monohydrate up to 40 95, povidone up to 7 Vol.

The tablet may have a shell containing hydroxypropylmethylcellulose, partially hydrolyzed polyvinyl alcohol, titanium dioxide, macrogol, triacetin, talc, lactose, dyes.

In the preparation of the proposed drug, in all cases, available as pharmacopoeial drugs and as chemical reagents, the substances of the specified ingredients, which had a quality not lower than "HC" (chemically pure), served as raw materials.

The production of experimental samples of preparations includes the following operations: calculation of the required doses using methods known to specialists and weight dosing of the selected dry ingredients. It is clear to an expert that the preparation of solid dosage forms with the necessary content of substances does not present any particular difficulties. It is also clear to the specialist that the preparation of injection dosage forms with the required content of substances also does not present particular difficulties: dissolving the specified substances in an isotonic solution of sodium chloride with the addition of ethyl alcohol or propylene glycol as solubilizers to obtain the required concentrations of active substances.

The above description is intended only as an illustration of the principles of a useful model. Moreover, since numerous modifications and changes will be apparent to those skilled in the art, it is not desirable to limit the utility model to the precise interpretation and methods described above.

Accordingly, all suitable modifications and equivalents within the scope of this utility model may be made in accordance with the Utility Model Formula.

Sources of information:: 1. Compendium 2006. Medicinal preparation / Ed. Kovalenko V.N., Viktorova A.P. -

K.: Morion, 2006. - P. 168. 2. Compendium 2006. Medicinal preparations / Ed. Kovalenko V.N., Viktorova A.P. -

K.: Morion, 2006. - P. 1573.

Claims (7)

USEFUL MODEL FORMULA 1. Combined medicinal product containing an agent with an analgesic effect and antispasmodic agents pitophenone hydrochloride and fenpiverine bromide in a pharmaceutically acceptable combination and auxiliary substances, which is distinguished by the fact that as an agent with an analgesic effect it contains the non-steroidal anti-inflammatory ketorolac tromethamine. 2. Combined medicinal product according to claim 1, where it exists in the form of a solution. 3. Combined medicinal product according to claim 2, where auxiliary substances are sodium chloride, propylene glycol, ethyl alcohol, disodium edetate, sodium hydroxide, water for injections. 4. Combined medicinal product according to claim 1, where it exists in the form of a tablet. 5. Combined medicinal product according to claim 4, where auxiliary substances are microcrystalline cellulose, crospovidone, starch, magnesium or calcium stearate. 6. Combined medicinal product according to any of claims 4-5, which may additionally contain excipients such as croscarmellose sodium, colloidal silicon dioxide, lactose monohydrate, povidone. 7. Combined medicinal product according to any of claims 4-6, where the tablet can have a shell containing hydroxypropylmethylcellulose, partially hydrolyzed polyvinyl alcohol, titanium dioxide, macrogol, triacetin, talc, lactose, dyes.