Novel pharmaceutic composition and its application in method of treatment of patients with hyperaemia and edema of mucous membrane of upper airways

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to medicine and can be applied for treatment of hyperaemia and edema of mucous membrane of upper airways. For this purpose introduced is loratadine or proper quantity in form of its acceptable salt in combination with phenylephrine or as monomedication. Loratadine is introduced in regimen 2.5 mg four times per day, and phenylephrine is introduced in regimen 8-10 mg four times per day. Loradadine introduction in regimen 2.5 mg per day makes it possible to reach high efficiency of treatment in absence of side reactions.

EFFECT: treatment efficiency by loratadine in combination with phenylephrine in claimed regimen is conditioned by their synergetic effect as well as in absence of side reactions.

28 cl, 3 tbl, 1 ex

 

Introduction

The present invention relates to pharmaceutical compositions comprising loratadine, for its use in the treatment of hyperemia and edema of the mucous membrane of the upper respiratory tract and to the method of introduction of this composition. Specifically, though not exclusively, this invention relates to a pharmaceutical composition comprising loratadine in quantities suitable for the introduction of a maximum of 4 times per day, and the second active agent is a hydroxyl-α-[(methylamino)methyl]-benzoimidazol, such as 3-hydroxyl-α-[(methylamino)methyl]-benzoimidazol (phenylephrine)or its salt.

Prior art

Hyperemia and edema of the mucous membrane of the upper respiratory tract caused by infections, such as colds and flu, or allergic rhinitis, can cause a number of symptoms associated with nose and eyes. They include rhinitis and sinusitis, congestion and swelling of the nose and sinuses, or excessive secretions, headaches, sneezing, and itching and excessive tearing. Infections such as colds, can be quite common in the winter months, while rhinitis symptoms are also common in several parts of the world.

Such symptoms can be treated with products containing antipruritic agents, and products containing decongestants. These products are usually sold as part of karstenii funds without prescription that are available for patients in retail outlets such as pharmacies.

There are a number available antihistamine active agents, including nnegative antihistamine agents, such as loratadine, cetirizine or Fexofenadine. These products give less sedative effect compared with conventional antihistaminic agents and, therefore, allow the consumer to more easily perform tasks such as driving a car or operate the equipment.

Fexofenadin is an active carbonisation metabolite of terfenadine. The last was withdrawn from use because of the dangerous cardiotoxic reactions and interactions with other medicines. For Fexofenadine not available in-depth information regarding the risk of these reactions. But, according AHFS Drug Information 2004, as a result, comparative studies of Fexofenadine and terfenadine believe that the clinical efficacy of terfenadine can be attributed to Fexofenadine. The risk of reactions similar to reactions to terfenadine produced by the application of Fexofenadine, is not excluded.

Cetirizine is another nesecarily antihistaminic agent. However, compared with loratadine, reported that cetirizine has a higher frequency of adverse reactions (ADR), especially ADR1in Rel is the decision of the Central nervous system. Some studies have also shown that cetirizine gives a higher incidence of drowsiness than loratadine.

Loratadine is disclosed in U.S. patent No. 4282233 as nesecarily antihistamine agent, useful as an antiallergic agent, for example, in the treatment of symptoms of seasonal allergic rhinitis such as sneezing and itching. Loratadine is the maximum dose nonprescription (OTC, over-the-counter), 10 mg per day. It is usually injected once a day at the maximum dose for a number of reasons, including the perceived effectiveness and patient compliance with the regimen and the regimen. However, there are negative effects that can occur when peak concentrations and also decreasing effect at the end of a dose.

Also there are a number of available decongestants. In the past, as decongestant used phenylephrine. However, its use now exceeds the next generation decongestant products, including pseudoephedrine. Pseudoephedrine has a tendency to act with greater efficiency and has a slightly longer half-life than the previous generation, such as phenylephrine, providing increased efficiency for easing symptoms.

As a result of demand for combined products that solve problems related the data with ingestion of many products, there are combinations of antihistamines and decongestant products. Been disclosed combination loratidine and decongestants new generation, such as pseudoephedrine, in order to enter this combination once or twice a day. Disclosure of such combinations, for example, in WO 98/18470 (Schering Corporation).

Combination decongestant medicines over the old type, such as phenylephrine, and sedative antihistamine agents are available in liquid preparations. The use of such products, however, has been supplanted by the use of combinations using decongestant medicines over of a new type, such as pseudoephedrine, for the reasons outlined above.

Currently, there are several solid dosage products that combine drugs more new type, such as pseudoephedrine, along with nnegative antihistaminic agents. Examples : these products are available in Australasia, are given in Table 1, below.

Table 1
Currently available in Australasia combination nakedteenage antihistamines and nasal decongestants products in the form of solid dosage forms
is already installed DecongestantNesecarily antihistaminic agentDaily dose
Clarinet 12 hoursPseudoephedrine 240 mgLoratadine 5 mg1 tablet twice a day
Clarinet relief at 24 hoursPseudoephedrine 240 mgLoratadine 10 mg1 tablet per day
Demazin necrotomyPseudoephedrine 240 mgLoratadine 5 mg1 tablet twice a day
Telfast decongestantPseudoephedrine 240 mgFexofenadine 60 mg1 tablet twice a day
Zyrtec decongestantPseudoephedrine 240 mgCetirizine 5 mg1 tablet twice a day

However, products containing pseudoephedrine, currently subject to dependency problems associated with the illicit use of drugs in society Pseudoephedrine component of these medicines can be turned into a powerful stimulant, such as methamphetamine and methcathinone, which are both Central nervous system stimulant with a high potential for addiction and physical and/or psychological dependence. This has led to robberies of pharmacies, theft of goods from warehouses and significantly related crime. The resulting crime and its impact on retail outlets that supply these medicines to the market means that some outlets are chosen by the absence of these products in the sale or at least limit their availability. This makes them less accessible for those who have a genuine need for these medicines. In the United States, for example, the law limits the threshold content of pseudoephedrine products OTC ("nonprescription"), for example, can contain no more than 3 grams of pseudoephedrine (in terms of basis)that is packaged in packaging with 1 or 2 units of dose on the packaging or in the form of liquid preparations, the packaging size.

It would be useful to have an alternative remedy which may be available without a prescription which is effective in the treatment of symptoms of hyperemia and edema of the mucous membrane of the upper respiratory tract and which reduces at least some of the problems identified above.

Other tasks of this the image is to be placed may become apparent from the following description, which is shown for example only.

Summary of the invention

In the first aspect according to the present invention, a method for treatment of hyperemia and edema of the mucous membrane of the upper respiratory tract by injecting the patient who needs it, the pharmaceutical composition comprising about 2.5 mg loratidine or a suitable salt, four times per day.

Preferably the composition is administered qid (four times daily).

Preferably this pharmaceutical composition further includes a hydroxy-α-[(methylamino)methyl]-benzoimidazol, most preferably 3-hydroxy-α-[(methylamino)methyl]-benzoimidazol (phenylephrine)or a suitable salt.

Preferably this pharmaceutical composition comprises from about 8 to 10 mg of free base of phenylephrine or corresponding amount in the form of a suitable salt.

Preferably the salt of phenylephrine is a cleaners containing hydrochloride salt.

Preferably, this pharmaceutical composition is a solid dosage form.

In one embodiment according to the present invention, a method for treatment of hyperemia and edema of the mucous membrane of the upper respiratory tract using a pharmaceutical composition that includes from about 8 to 10 mg of free base of the phenyl is frina or corresponding amount in the form of a suitable salt and about 2.5 mg loratidine or corresponding amount in the form of a suitable salt, where the patient is given this song four times a day.

Preferably this pharmaceutical composition is administered qid.

Preferably the salt of phenylephrine is a cleaners containing hydrochloride salt. More preferably the composition comprises from 10 to 12.2 mg cleaners containing hydrochloride salt.

Preferably, this method includes the introduction of pills, capsules or tablets containing from about 8 to 10 mg of phenylephrine and about 2.5 mg loratidine or the corresponding amount in the form of suitable salts, 4 times a day.

In another aspect according to the present invention proposed the use of approximately 8 to 10 mg of phenylephrine and about 2.5 mg loratidine or the corresponding amount in the form of suitable salts in the manufacture of a medicinal product for administration to the patient 4 times a day to treat hyperemia and edema of the mucous membrane of the upper respiratory tract.

Preferably this medicine manufactured for the introduction of qid.

Preferably phenylephrine is in the form of a salt, more preferably in the form of cleaners containing hydrochloride salt.

In another aspect according to this invention proposed pharmaceutical composition for the treatment of hyperemia and edema of the mucous membrane of the upper respiratory tract, containing phenylephrine or a suitable salt and loratadine or its suitable with the ü, where the phenylephrine is present in an amount of about 8 to 10 mg, loratadine is present in amount of about 2.5 mg

Preferably the salt of phenylephrine is cleaners containing hydrochloride salt.

Preferably this pharmaceutical composition includes a pharmaceutically acceptable inactive excipients and/or carriers.

Preferably, this pharmaceutical composition is a pill, capsule or tablet.

In one embodiment, this pharmaceutical composition is a 10,00 mg of phenylephrine hydrochloride, 2,50 mg loratidine, 180,40 mg of lactose, 140,00 mg of corn starch, 10,365 mg pregelatinization starch, 0.20 mg varnish quinoline yellow, and 0.40 mg of sodium metabisulphite, 0.14 mg disodium salt EDTA, 3,00 mg of talc and 3,00 mg of magnesium stearate.

In another aspect according to this invention proposed a package containing pills, tablets or capsules containing pharmaceutical composition comprising phenylephrine and loratadine where the phenylephrine is present in an amount of about 10 mg, loratadine is present in an amount of about 2.5 mg where this package includes instructions introduction this composition a maximum of 4 times per day.

Preferably phenylephrine is in salt form, most preferably in the form of cleaners containing hydrochloride salt.

Preferably the introduction of 4 times the day is a qid.

Preferably the packaging is a blister pack.

In another aspect according to this invention proposed a container containing syrup, containing loratadine and phenylephrine, or their suitable salts in concentrations suitable for the introduction of approximately 2.5 mg loratidine and from about 8 to 10 mg of phenylephrine on the standard dose, the vial includes instructions for introducing quantity of the syrup, which will deliver approximately 2.5 mg loratidine and from about 8 to 10 mg of phenylephrine on the standard dose 4 times a day.

Preferably phenylephrine is in the form of a salt, more preferably in the form of cleaners containing hydrochloride salt.

In alternative aspects according to this invention proposed the use of approximately 2.5 mg loratidine in the manufacture of drugs for the treatment of hyperemia and edema of the mucous membrane of the upper respiratory tract; where this drug is preferably intended for the introduction of a maximum of four times per day.

Preferably, the applying further includes applying from 8 to 10 mg of the appropriate phenylephrine, preferably corresponding amount in the form of a suitable salt, in the manufacture of this drug.

In another aspect according to this invention proposed pharmaceutical composition for use in the treatment of hyperim and and swelling of the mucous membrane of the upper respiratory tract, this composition comprises 2.5 mg loratidine together with pharmaceutically acceptable carriers and/or excipients.

It is understood that the reference to "treatment hyperemia and edema of the mucous membrane of the upper respiratory tract includes the treatment of the symptoms of hyperemia and edema of the mucous membrane of the upper respiratory tract, such as rhinitis, sinusitis, congestion and swelling of the nose and paranasal sinuses, excessive secretions, headaches, sneezing, itching, and/or excessive tearing. Treatment should be understood in terms of ease or mitigate, but not cure.

When you use the phrase "appropriate amount" in respect of a number of suitable salts, means the amount of salt required to ensure an equivalent dose of free bases, for example to 12.2 mg of phenylephrine hydrochloride is an amount corresponding to 10 mg of phenylephrine in the form of free base.

A detailed description of the preferred embodiments

According to this invention, in General terms, a method of treatment of hyperemia and edema of the mucous membrane of the upper respiratory tract using a pharmaceutical composition, which includes loratadine in quantities suitable for injection 4 times a day. The composition additionally includes a decongestant.

In addition, the author of this image is the shadow set, the choice of decongestant, representing a hydroxyl-α-[(methylamino)methyl]-benzoimidazol or its salts, does not lead to disadvantages that arise due to the choice of this decongestant as α-[1-(methylamino)ethyl]-benzoimidazol.

Lower efficiency and shorter half-life of the selected decongestant can be compensated, at least to a limited extent, its use in combination with loratadine. The benefits of this specific combination has not been previously defined for the compositions disclosed in the descriptions of international application number PCT/IB03/01197 (no publication WO 03/089007) or international application no PCT/US2003/029095 (no publication WO 2004/023984).

This composition contains loratadine (nesecarily antihistamine agent) and preferably phenylephrine (a decongestant). This pharmaceutical composition is safe for delivery, do not on the basis of prescription and, therefore, can be bought as a means of over-the-counter ("OTC").

Table 2
The dose levels of phenylephrine and pseudoephedrine
AgentDoseLink
Phenylephrine 10 mg 3-4 times a dayMartindale 28th edition
10 mg every 4 hoursDrug Tx, 4th edition
Pseudoephedrine60 mg 3-4 times per dayMartindale 28th edition
60 mg qid or 120 mg bd (twice a day)Drug Tx, 4th edition

As stated in the link Martindale, you can use a number of suitable salts of phenylephrine.

Fenilefrina component can be delivered in any suitable salt form (for example, in the form of HCl salt, tartrate). You can also use the form of the base. Suitable salts are known to the person skilled in the art. Assume that here is the link to the application of phenylephrine includes a reference to delivery in the form of a suitable salt.

Loratadine is the maximum daily introduction OTC 10 mg per day. As with phenylephrine for delivery loratidine you can also use suitable salts, as known to the person skilled in the art. Assume that here is the link to loratadine includes an introduction in the form of a suitable salt.

It is surprising that the use of approximately 2.5 mg loratidine, administered 4 times per day (e.g., qid), has a therapeutic beneficial is above the normal 10 mg, enter once per day. It is assumed that this may be due to the ideal profile of the concentration-time in order to have a long lasting effect was constant concentration over time (which would occur during continuous infusion). As the use of 2.5 mg loratidine evens out the differences between the maximum and minimum concentrations in plasma, this mode of administration has the closest resemblance to the effect of continuous infusion. The flatter profile of the concentration-time benefits fewer negative effects peak concentrations and a smaller reduction effect at the end of a dose. Introduction this composition gives the patient a clear advantage in terms of the effect of loratidine. This effect forms the basis of one aspect of the present invention.

While for the treatment of hyperemia and edema of the mucous membrane of the upper respiratory tract is known to use a combination nakedteenage antihistamine agent and decongestant, it now includes the latest generation decongestant medicines and usually includes the use of maximum doses of active ingredients of OTC single administration. Phenylephrine, drug earlier generation, is different from pseudoephedrine activity when compared on the basis of milligrams. Development Deco is gestantes, such as pseudoephedrine, which provide more efficient ways to reduce swelling, means that decongestants are of an older generation such as phenylephrine, are not active agents, which are usually included in the combined drugs. The development of a product containing loratadine and phenylephrine, which provides therapeutic benefits and advantages in the application of the present invention, therefore, is unexpected and represents a significant progress.

The author of the present invention found that the use of the drug more than the old generation (phenylephrine), although it is less effective, still gives, in combination with an effective resedation antihistamine agent, a useful drug to relieve symptoms of hyperemia and edema of the mucous membrane of the upper respiratory tract.

Introduction the combination comprising phenylephrine (preferably in the form of a suitable salt, for example, hydrochloride, tartrate), 4 times a day (for example, preferably qid) provides therapeutic benefits and advantages in the application of that soften therapeutic effect of drugs over the old type, along with additional advantages. This ensures that alternative medicines among the CTB is available for those suffering from symptoms without limitation, imposed on availability of this drug, because of the social problems arising from the use of drugs is more of a new type. When using such medicines over the old generation in combination with resedation antihistamine means the author of the present invention has also established the importance of minimizing the possibility of adverse reactions to the drug.

The introduction of phenylephrine 4 times a day delivers peak effects of this medication four times during the day, reducing, thus, the effect of rapid half-life of phenylephrine on decongestant efficiency. It is the combination of preferably four times the introduction of loratidine and phenylephrine and interaction effects between them ensures that this pharmaceutical composition gives the consumer such a useful alternative combinations that use decongestant new medicines type. Perhaps phenylephrine may be included so that he was slowly released from this composition, but it is believed that this is not necessary. From this point of view, the combined effect of these two drugs with the introduction of 4 times per day may be called synergy. It is the combination of the useful effects, derived from preferably four times the introduction of both drugs, which allows consumers to benefit, excess benefit, provide a simple introduction to these medicines separately or in combination to meet the maximum daily dose in the introduction of one or two times a day. Introduction for the treatment of severe symptoms is the introduction of 4 times per day and is close to the qid as soon as possible. This serves to maximize the benefits obtained from flat peak/minimum concentrations of loratidine in the plasma. This allows the composition to provide a useful alternative to existing songs, using the new generation of decongestants, from the point of view of efficiency, and ensures that the composition does not suffer from social problems that hinder the use of decongestants new generation (e.g., pseudoephedrine). This combined effect (loratidine and phenylephrine) forms the basis of another or additional aspect of the present invention.

The treatment regimen of 2.5 mg or 2.5 mg/10 mg qid in fact has disadvantages compared with other schemes in terms of adherence to treatment regimens. Scheme once a day and twice a day surpass scheme qid in terms of adherence to the scheme is ecene. However, adherence and treatment regimens are also associated with the severity of symptoms, and patients usually remind you that you need to follow a schedule and regimen, if their symptoms persist. In this case, failure mode and treatment when symptoms have abated, probably, is not a disadvantage. While the introduction once a day or twice a day may have advantages in adherence and treatment, the beneficial effects 2.5 mg loratidine 4 times per day (e.g., qid) in the treatment of severe symptoms of hyperemia and edema of the mucous membrane of the upper respiratory tract separately or together with phenylephrine is still significant.

The pharmaceutical combination according to this invention provides for the delivery of a total of about 10 mg loratidine and 40 mg of phenylephrine per day, administered in 4 doses. This pharmaceutical composition will include loratadine in an amount of about 2.5 mg and phenylephrine (preferably in the form of cleaners containing hydrochloride salt) in an amount of about 10 mg of the Number of active substances used in the composition will, of course, be within the tolerances that are acceptable for pharmaceutical use.

These compositions also include inactive components, such as binders and other excipients known to the person skilled in the art. Data ingredient which can be prepared in the form of tablets, pills or capsules using known pharmaceutical carriers and excipients, such as diluents, binders, colorants, antioxidants, chelating agents, sliding agents and/or lubricants). This composition is prepared in the form of a tablet size that can contain the preferred amounts of ingredients. Preferably this composition is manufactured using a pharmaceutically acceptable ingredients, as known to the expert, such as corn or pregelatinized starch, lactose (e.g., monohydrate), microcrystalline cellulose, magnesium stearate, quinoline yellow, sodium metabisulfite, ethylenediaminetetraacetic acid (EDTA), talc.

Preferably will use purified water. As will be clear to experts in this field, the purified water can be used during the cooking process, which includes the drying process. In the process of drying of the composition of the evaporated water, which means that water does not contribute to the final weight of this composition.

Tablets/pills will preferably be presented to the consumer as part of pharmaceutical packaging, such as blister packing, as is well known. This package must have an integer number of pills contained therein, and to have instructions on max the m number of pills/tablets, subject to acceptance at any one time and within a set time frame. In this case, one tablet/pill/capsule should be taken 4 times a day (preferably qid). Of course, it is possible that these pills/tablets/capsules can be sold contained in the vial, and the pills are kept in the bottle freely. Again will include instructions introduction 4 times a day (preferably qid).

In another alternative embodiment, this pharmaceutical composition can be a syrup for introducing children and patients who have difficulty swallowing pills. Standard methods for such syrups are well known in this field. This syrup is contained in a bottle, vial or similar container, and get it a way that allows the delivery of approximately 2.5 mg loratidine and preferably about 10 mg of phenylephrine per dose 4 times a day. This is achieved by obtaining a syrup containing a certain concentration of active agents, in combination with instructions on how much syrup should be taken in dose four times per day. As for doses for younger children, it will be clear that suitable are lower doses of this syrup. As for loratidine, dose for children under 12 years must be less than 5 mg/day.

With edutella, we can assume that this invention is a method for the treatment of hyperemia and edema of the mucous membrane of the upper respiratory tract in a patient in need thereof, using a pharmaceutical composition comprising about 2.5 mg loratidine and preferably about 10 mg of phenylephrine, which is injected to the patient 4 times a day. This pharmaceutical composition itself is also an object of the invention, as the use of approximately 2.5 mg loratidine and preferably about 10 mg of phenylephrine in the manufacture of drugs for such treatment.

The preferred composition shown in Table 3 below.

Example

The components shown in Table 3, are combined into one pill and accept them either adults or children aged 12 years or older. This pill can be taken up to 4 times per day, providing a maximum dose of 10 mg loratidine and 40 mg of phenylephrine in the day.

Table 3
The drug combination composition
Name of ingredientThe number on pillFunctionLink description
- Active and gradient
Phenylephrine hcl10,00 mgThe active ingredientPh. Eur.
Loratadine2,50 mgThe active ingredientIHS
- Other ingredients
Lactose180,40 mgThinnerPh. Eur.
Corn starch140,00 mgThe diluent, binderPh. Eur.
Pregelatinized starch10,365 mgBinderPh. Eur.
Lacquer quinoline yellow0.20 mgDyeIHS
Metabisulphite sodium0,40 mg AntioxidantPh. Eur.
The disodium salt of EDTA0.14 mgChelating agentPh. Eur.
Talc3,00 mgMoving substancePh. Eur.
Magnesium stearate3,00 mgGreasePh. Eur.

The drug, administered 4 times per day, provides 24-hour effective treatment of the symptoms of hyperemia and edema of the mucous membrane of the upper respiratory tract with reduced negative effects and without the use of pseudoephedrine as decongestant.

Where in the above description, reference was made to specific components or integers of the invention having known equivalents, then such equivalents are included in this description of the invention as set forth separate.

Although this invention was described only as an example and with reference to possible embodiments, it should be understood that it is possible to make modifications or improvements without deviation from the scope or the invention as defined in the Appendix the military claims.

Links:

(1) The American Society of Health System Pharmacists Drug Information 2004. G.K. McEvoy (Editor), Bethesda, USA.

1. Way to treat hyperemia and edema of the mucous membrane of the upper respiratory tract by injecting the patient who needs it, the pharmaceutical composition comprising about 2.5 mg loratidine or corresponding amount in the form of a suitable salt together with hydroxy-α-[(methylamino)methyl]-benzoimidazole or a suitable salt, four times per day.

2. The method according to claim 1, where the composition is administered every 6 hours

3. The method according to claim 1 where the pharmaceutical composition comprises 3-hydroxy-α-[(methylamino)methyl]-benzoimidazol(phenylephrine) or a suitable salt.

4. The method according to claim 3, where the pharmaceutical composition comprises from about 8 to 10 mg of free base of phenylephrine or corresponding amount in the form of a suitable salt.

5. The method according to claim 4, where the salt of phenylephrine is a cleaners containing hydrochloride salt.

6. The method according to any one of claims 1 to 5, where the pharmaceutical composition is a solid dosage form.

7. The method according to claim 1, where the composition includes from 10 to 12.2 mg cleaners containing hydrochloride salt of phenylephrine.

8. The method according to any one of claims 1 to 6, including the introduction of pills, capsules or tablets containing from about 8 to 10 mg of phenylephrine and about 2.5 mg loratidine or the corresponding amount in the form of suitable salts, 4 p is for night.

9. The use of approximately 8 to 10 mg of phenylephrine and about 2.5 mg loratidine on the dosage form or the relevant quantities in the form of suitable salts in the manufacture of a medicinal product for administration to the patient 4 times a day to treat hyperemia and edema of the mucous membrane of the upper respiratory tract.

10. The use according to claim 9, where the drug is made for injection every 6 hours

11. The use of claim 10, comprising phenylephrine in salt form.

12. The application of claim 11, where the salt of phenylephrine is a cleaners containing hydrochloride salt.

13. Pharmaceutical composition comprising about 2.5 mg loratidine or corresponding amount in the form of a suitable salt together with hydroxy-α-[(methylamino)methyl]-benzoimidazole or a suitable salt intended for use in the treatment of hyperemia and edema of the mucous membrane of the upper respiratory tract by injecting the patient four times a day.

14. The composition according to item 13, including phenylephrine in the amount of from 8 to 10 mg.

15. The pharmaceutical composition according to item 13, where the phenylephrine is in the form of cleaners containing hydrochloride salt.

16. The pharmaceutical composition according to item 13, which includes pharmaceutically acceptable inactive excipients and/or carriers.

17. The composition according to item 13 for injection every 6 hours

18. Pharmaceutical composition for the .13 in pill form capsules or tablets.

19. The pharmaceutical composition according to any one of p-18, including approximately 10,00 mg of phenylephrine hydrochloride, 2.5 mg loratidine, 180,40 mg of lactose, 140,00 mg of corn starch, 10,365 mg pregelatinization starch, 0.20 mg varnish quinoline yellow, and 0.40 mg of sodium metabisulphite, 0.14 mg disodium salt ethylenediaminetetraacetic acid (EDTA), 3,00 mg of talc and 3,00 mg of magnesium stearate.

20. The pharmaceutical composition according to any one of p-18, presented in the form of packaging of pills, tablets or capsules comprising instructions introduction this composition a maximum of 4 times per day.

21. The container containing syrup, containing loratadine and phenylephrine, or their suitable salts in concentrations suitable for the introduction of approximately 2.5 mg loratidine and from about 8 to 10 mg of phenylephrine per dose, where the container includes instructions for introducing quantity of the syrup, which will deliver approximately 2.5 mg loratidine and from about 8 to 10 mg of phenylephrine 4 times a day.

22. The container according to item 21, where the phenylephrine is in the form of salts.

23. The container according to item 22, where the phenylephrine is in the form of cleaners containing hydrochloride salt.

24. Way to treat hyperemia and edema of the mucous membrane of the upper respiratory tract by injecting the patient who needs it, the pharmaceutical composition comprising about 2.5 mg loratidine and the and the corresponding amount in the form of a suitable salt as the sole therapeutically active ingredient to four times per day.

25. Pharmaceutical composition comprising about 2.5 mg loratidine or corresponding amount in the form of a suitable salt intended for administration to the patient four times a day to treat hyperemia and edema of the mucous membrane of the upper respiratory tract.

26. The use of approximately 2.5 mg loratidine on the dosage form or the appropriate number in the form of a suitable salt in the manufacture of pharmaceutical compositions for administration to the patient four times a day to treat hyperemia and edema of the mucous membrane of the upper respiratory tract.

27. Packaging, including pills, pills, or capsules containing pharmaceutical composition, comprising loratadine in an amount of about 2.5 mg where this package includes instructions introduction this composition a maximum of 4 times per day.

28. Packaging according to item 27, where the specified pharmaceutical composition additionally contains phenylephrine in an amount of about 8 to 10 mg.



 

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7 cl, 9 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: in formula (I) Cy1 is a 6-member heterocyclyl containing N as a heteroatom, a 5,6-member monocyclic or 9,10-member bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S and O, phenyl or phenyl condensed with a 5-member heterocycle containing O as a heteroatom, each optionally having 1-3 identical or different substituting Cy1 groups which are: (C1-C6)-acyl, cyano, carboxy, hydroxy, (C1-C6)alkylsulphonyl, (C3-C6)-cycloalkyl, a 6-member heterocyclyl containing 1-2 heteroatoms selected from O and N, phenyl, a 5-member heteroaryl containing 1-3 heteroatoms selected from N, S and O, Y1Y2N-, Y1Y2NC(=O)-, Y1Y2NSO2-, (C1-C6)-alkyl-SO2-N(R5)-C(=O)-, R6-C(=O)-N(R5)-, R7-NH-C(=O)-NH-; (C1-C6)-alkoxycarbonyl; (C1-C6)-alkyl, which optionally contains 1-3 identical or different substitutes which are halogen, carboxy, cyano, hydroxy, Y1Y2N-, Y1Y2N-C(=O)-, R6-C(=O)-N(R5)-, R8-SO2-N(R5)-C(=O)-, 5-member heterocyclyl, containing N as a heteroatom, 5-member heteroaryl containing 1-3 heteroatoms selected from N and O; or (C1-C6)-alkoxycarbonyl; as well as (C1-C6)-alkoxy which optionally have 1-3 identical or different substitutes which are carboxy, (C1-C6)-alkoxycarbonyl, cyano, 3-member heterocyclyl containing O as a heteroatom, or 5-member heteroaryl containing 1-3 heteroatoms selected from N and O; where phenyl or heteroaryl fragments in the substituting Cy1 groups optionally and independently have substitutes represented by hydroxy, (C1-C6)-alkyl, (C1-C6)-alkoxy, carboxy, (C1-C6)-alkoxycarbonyl or R8-SO2-N(R5)-C(=O)-; and where cycloalkyl fragments in the substituting Cy1 groups which optionally and independently have substitutes represented by (C1-C6)-alkoxy, carboxy; Cy2 is a 9-member cycloalkenyl, phenyl, 5,6-member monocyclic or 9,10-member bicyclic heteroaryl containing 1-3 heteratoms selected from N, S and O, or phenyl condensed with a 5,6-member heterocycle containing 1-2 heteroatoms selected from N and O, each independently and optionally having 1-3 identical or different substitutes represented by (C1-C6)-alkoxy, (C1-C3)-alkyl, hydroxy, halogen, halogen-(C1-C6)-alkoxy, nitro, Y1Y2N-; L1 is an alkylene with a straight or branched chain containing 1-6 carbon atoms, optionally substituted carboxy; or L1 is -CH2-(C1-C5)halogenalkylene; L2 is a bond, -O- or -CH2-O-. Other values of radicals are given in the formula of invention.

EFFECT: novel compounds have prostaglandin D2 receptor antagonist properties, can be used in treating primarily allergic disorders such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy and other diseases.

39 cl, 1 tbl, 99 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to application in an effective amount and to new nicotine receptor agonists described by general formula (i) or (ii) for treating inflammatory diseases chosen from a group including asthma, chronic obstructive pulmonary disease (COPD), interstitial pulmonary tissue fibrosis (IPF), sarcoidosis, hypersensitivity pneumonitis (HP), chronic hypersensitivity pneumonitis and bronchiolitis obliterans organising pneumonia (BOOP). The compounds (i) and compounds (ii) relate to formulae (i) (ii) where in formula (i) R1 and R2 independently mean alkyl with 1-10 carbon atoms; Xa means CH or N; Ya means one or more substitutes chosen from hydrogen, halogen, cyano, hydroxyl, alkyl with 1-10 carbon atoms optionally substituted with one or more halogen atoms, and alkoxy with 1-10 carbon atoms; n means an integer 0 or 2; J means a counterion representing a compound for maintaining electric neutrality, e.g., halogen, sulphate, sulphonate; in formula (ii) R3 is chosen from or Xb means N or N+-R10; R4 means one or more substitutes chosen from hydrogen, halogen; each R10, R11 and R12 independently means alkyl with 1-10 carbon atoms; provided the presence of the counterion when Xb means N+-R10.

EFFECT: use of nicotine receptor agonists in the effective amount for treating inflammatory diseases.

26 cl, 40 dwg, 3 tbl, 38 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns cat allergen fused proteins and application thereof. Substance of the invention involves a compositions containing a virus-like particle (VLP) or a viral particle and at least, one antigen, first of all at least, one cat antigen, and more specifically at least one cat antigen which is human allergen. In specific versions of the invention, said antigen represents cat antigen Fel d1 or its fragment covalently bound with the VLP.

EFFECT: invention can be applied for preparing vaccines first of all aimed at treatment and/or prevention of cat dander allergy and other cat antigens and allergens responses.

25 cl, 20 ex, 5 tbl, 4 dwg

FIELD: medicine.

SUBSTANCE: daily in morning hours nasal passages are washed with physiological solution, 10% oil solution of vitamin E in dose 3 drops into each passage is dropped into both nasal passages. After 2 hours transcutaneous impact with constant magnetic field and low-intensity laser irradiation with power 30-80 mW, wavelength 0.85-0.89 mcm, pulse repetition rate 50-80 Hz is carried out on region of projection of thymus, maxillary sinuses, submandibular lymph nodes, spinous process of the third cervical vertebra, mastoid process. Time of impact is 60 seconds per each region. Ozonised olive oil is dropped into each nasal passage in dose 3 drops. After that, by means of light-conducting nozzle performed is impact on anterior parts of inferior nasal conchas with pulse red irradiation with wavelength 0.63-0.65 mcm, pulse power of irradiation at outlet not less than 5 W, pulse repetition rate 50-80 Hz, frequency of light diode modulation - 4-8 Hz. Impact time is 60-120 seconds. Total treatment course is 7 days with 4 month interval, 3 times per year. During the first interval between courses bacterial immunomodulator IRS-19 is introduced in age dose in therapeutic regimen. During the second interval antihomotoxic therapy with drugs Luffel and Lymphomyosot is administered.

EFFECT: method makes it possible to increase treatment efficiency, reduce frequency of disease recurrences, reduce medication load in case of allergic rhinites, which usually require long treatment.

2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to producing versions of group I Poaceae (holy grass) allergen, also can be used either for specific immunotherapy (hyposensitisation) of patients with grass pollen allergy, or for preventive immunotherapy of grass pollen allergies. The produced versions are characterised by Cys41 Ser, Cys57Ser, Cys69Ser, Cys72Ser, Cys77Ser, Cys83Ser and Cysl39Ser substitutes in a Phi p1 mature protein sequence. Also, a structure of the allergen versions can be presented with no fragments relevant to amino acid residues 1-6, 1-30, 92-104, 115-119, 175-185 and 213-220 or 1-6, 115-119 and 213-220 as a part of a primary sequence of Phi p1 mature protein.

EFFECT: invention allows producing a version of group I Poaceae allergen characterised lower IgE responsiveness as compared with common wild allergen and substantially maintained responsiveness to T-lymphocytes.

8 cl, 9 dwg, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to application of N-acyl derivatives of amino acids of general formula

, where n equals 2 or 3 and their pharmaceutically acceptable salts as anti-allergic, anti-inflammatory and anti-anaphylactic medications.

EFFECT: obtaining pharmaceutical composition for treatment of allergic and inflammatory diseases, for instance such as bronchial asthma, allergic rhinitis, pollinosis, psoriasis.

11 cl, 12 tbl, 19 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to peptides inhibiting mucin hypersecretion. The peptides have an amino acid sequence containing up to 24 amino acid residues of the sequence GAQFSKTAAKGEAAAERPGEAAVA which can have at least one amino acid substitute in said sequence selected from a group consisting of the substitute of A by K, the substitute of F, K, G, Q, S, T and/or E for A; or the substitute of Q for E.

EFFECT: preparation of a pharmaceutical composition on the basis of the peptides for mucin hypersecretion inhibition.

28 cl, 9 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to inhibiting or decreasing a level of inflammation mediator release from inflammatory cells by suppressing a mechanism associated with inflammation mediator release from inflammatory cell granules by using the versions of MANS peptide.

EFFECT: invention refers to an endocellular signal transmission mechanism which allows detecting a number of new endocellular targets for the pharmacological treatment of disorders associated with inflammation mediator secretion from inflammatory cell vesicles.

25 cl, 15 dwg, 6 ex

FIELD: medicine.

SUBSTANCE: claimed is application of solid peroral dosing composition of prolonged action, which includes (a) core, containing effective amount of pseudoephedrine or its salt, (b) first envelope, covering core and including swelling in water film-forming neutral or cationogenic copolymer ester, film modifier and lubricating substance, and (c) second envelope, covering first envelope and including effective amount of desloratadine, amount of pseudoephedrine or its salt is sufficient for ensuring maximaum of average geometrical values of pseudoephedrine concentration in plasma, from 345 to 365 ng/ml, for the time from 7.60 to 8.40 h, and amount of desloratadine is sufficient for ensuring maximum of its average geometrical values of concentration in plasma, from 2.10 to 2.45 ng/ml, for period from 4.0 to 4.5 h after intake of single dose of said composition, for preparation of medication for treatment of allergic and/or inflammatory states of upper and lower respiratory ways and skin, or urticaria and nasal and non-nasal symptoms of year-round and seasonal allergic rhinitis.

EFFECT: composition ensures necessary profile of active agents release and is efficient in treatment of allergic bronchospasm, couphing, seasonal allergic rhinites.

3 cl, 4 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention also relates to a non-solvated crystalline form of the hydrochloride salt of 5-[3-(3-hydroxyphenoxy)azetidin-1-yl]-5-methyl-2,2-diphenylhexanamide, a pharmaceutical composition, use of compounds in claim 1 or 2, as well as a method of treating a mammal with M3 antagonist.

EFFECT: obtaining novel biologically active compounds which have M3 antagonist activity.

9 cl, 6 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to field of pharmaceutics and medicine and deals with application of tiotropium bromide salt for obtaining medication, intended for treatment of patients, who suffer from severe form of persistent asthma.

EFFECT: invention insures high efficiency of treatment.

11 cl, 1 tbl, 22 ex

FIELD: medicine.

SUBSTANCE: offered are versions of IL-13 antibodies each of which contains respectively three CDR heavy and three CDR light chains. A pharmaceutical composition of antibodies for asthma treatment is described.

EFFECT: use of the invention can find further application in therapy of the IL-13 mediated B-cell disorders.

11 cl, 6 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine, namely to a new application of common indole derivatives for preparing a drug exhibiting the properties of a protein kinase C inhibitor. A preferential indole derivative is 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-oxy-6-bromindole hydrochloride.

EFFECT: compounds are effective protein kinase C inhibitors that allows them being used in treating inflammatory diseases, ischemia, cardiovascular diseases, dermatological diseases, asthma, diabetes.

3 cl, 3 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula , where R1 represents aryl, heteroaryl or (C5-C6)-cycloalkyl, each of which has an optional substitute halogen or (C1-C6)-alkyl; R2 represents hydrogen or (C1-C4)-alkyl; R3 represents -P(=O)-(alkoxy)2 or Y1Y2N-SO2-, cycloalkyl, aryl, heteroaryl, heterocyclyl, cycloalkenyl, each of which has an optional substitute: halogen, hydroxy, carboxy, Y1Y2N-, Y1Y2NC(=O)-, Y1Y2N-SO2, R7-SO2-NR6-, R7-C(=O)-NR6-, or alkyl, alkoxy, alkoxycarbonyl, each of which has an optional substitute halogen, -P(=O)-(alkoxy)2, Y1Y2NC(=O)-, Y1Y2N-SO2-, R7 -SO2-NR6 -, aryl or heteroaryl and when R3 is cycloalkyl, cycloalkenyl, heterocyclyl, it also optionally substituted by oxo; L1 represents a bond or (C1-C6)-alkylene, which is optionally substituted by -P(=O)-(alkoxy)2; R4, R5 and R6 are hydrogen, R7 represents alkyl; both Y1 and Y2 independently is hydrogen, alkyl which has an optional substitute: hydroxy, amino, alkylamino, dialkylamino, alkoxy, cycloalkyl, or Y1 and Y2 together with nitrogen atom whereto attached form heterocyclyl which optionally contains one more heteroatoms selected from oxygen, nitrogen or sulphur where heterocyclyl has an optional substitute alkyl or oxo; provided when L1 represents a bond, R3 is not optionally substituted by phenyl, optionally substituted by naphthyl, optionally substituted by benzoimidazolyl, optionally substituted by benzothiazolyl or optionally substituted by tetrazolyl; or to its pharmaceutically acceptable salt, and also to a pharmaceutical composition including a compound of formula I.

EFFECT: there are produced and described new compounds which can be effective in treating allergic or inflammatory disorders, particularly such disorders, as allergic rhinitis, asthma or chronic obstructive pulmonary disease.

25 cl, 118 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, pulmonology, and can be used for combination therapy of bronchial asthma. That is ensured by drug-induced therapy, supravenous blood laser irradiation and infrared magnetic-laser therapy (IR-MLT) of a projection area of adrenal glands The supravenous blood laser irradiation is carried out for 15 minutes at wave length 0.63 mcm, power 5 mWt by a light guide tip. The first and fifth IR-MLT procedures are preceded by examining cortisol and estradiol levels in females and testosterone level in males. If the cortisol level is lower than 230 nmol/l, and the testosterone level is lower than 500 ng/dl in males, and the estradiol level is lower than 30 pg/ml in non-menopause females and lower than 15 pg/ml in menopause females, pulse repetition rate is specified 150 Hz and "НМП" - 50 mT. If the cortisol level is 230 to 750 nmol/l, the estradiol level is 30 pg/ml to 160 pg/ml in females, and the testosterone level 260 to 1593 ng/dl in males, pulse repetition rate is specified 80 Hz and "НМЛ" 25 mT. Total exposure time for one session is no more than 18 minutes. The therapeutic course is 10-12 procedures.

EFFECT: method allows higher clinical effectiveness, reduced time of treatment, eliminates side effects, corrects the hormone level and allows reducing a dosage of the prescribed preparations.

1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medications and deals with combination of R,R-glycopyrrolate or its physiologically acceptable salts and montelukast in effective amount for treatment of respiratory diseases, selected from group, which includes allergic rhinitis, bronchial asthma, chronic obstructive lung diseases and common cold. Also described are pharmaceutical composition for treatment of respiratory diseases, which contains R,R-glycopyrrolate or its physiologically acceptable salts and montelukast in effective amount, and application of R,R-glycopyrrolate or its physiologically acceptable salts and montelukast or its physiologically acceptable salts in effective amount for preparation of pharmaceutical composition.

EFFECT: claimed combination inhibits release of IL-2 synergically.

15 cl, 5 ex

FIELD: medicine.

SUBSTANCE: claimed is application of solid peroral dosing composition of prolonged action, which includes (a) core, containing effective amount of pseudoephedrine or its salt, (b) first envelope, covering core and including swelling in water film-forming neutral or cationogenic copolymer ester, film modifier and lubricating substance, and (c) second envelope, covering first envelope and including effective amount of desloratadine, amount of pseudoephedrine or its salt is sufficient for ensuring maximaum of average geometrical values of pseudoephedrine concentration in plasma, from 345 to 365 ng/ml, for the time from 7.60 to 8.40 h, and amount of desloratadine is sufficient for ensuring maximum of its average geometrical values of concentration in plasma, from 2.10 to 2.45 ng/ml, for period from 4.0 to 4.5 h after intake of single dose of said composition, for preparation of medication for treatment of allergic and/or inflammatory states of upper and lower respiratory ways and skin, or urticaria and nasal and non-nasal symptoms of year-round and seasonal allergic rhinitis.

EFFECT: composition ensures necessary profile of active agents release and is efficient in treatment of allergic bronchospasm, couphing, seasonal allergic rhinites.

3 cl, 4 tbl, 4 ex

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