Antihistamine composition

 

(57) Abstract:

The invention can be used in medicine for the treatment of seasonal and perennial allergic rhinitis, conjunctivitis, hay fever, urticaria and other allergic reactions. The composition is made in the form of a syrup contains, g/100 ml: loratadine is 0.01 to 5.0; saccharide 10,0-70,0; alcohol 0,5-45, 0mm; pharmaceutically acceptable acid to create a pH of 2-4, water to 100 ml. pH of the composition is preferably of 2.5-3.5. It can optionally contain flavouring and colouring agents. The composition is stable when stored for a long time (not less than 2 years) and has good organoleptic properties. 3 C.p. f-crystals, 3 tables.

The invention relates to the field of medicine and is suitable for the treatment of seasonal and perennial allergic rhinitis, conjunctivitis, hay fever, urticaria, including chronic idiopathic urticaria, angioedema, psevdoallergicakie reactions caused by the release of histamine, itching dermatoses, allergic reactions to insect bites and itching of various etiologies.

In recent years a special place in therapy of allergic diseases took antihistamines (H1 blockers receptor), among which will peel off select lo is th acid), related to medicines of the last generation [Mashkovsky M. D. Medicines, T. I, ed.13th, Kharkov: Torsing, 1997, S. 283]. The connection blocks histamine H-1 receptors, which determines its antiallergic, antipruritic and protivoekssudativnoe action. The effectiveness of loratidine in a single application per day, the lack of sedative and anticholinergic actions makes it attractive is its use not only for the treatment of adult patients and in pediatric patients.

In the latter case, the obvious advantage, especially for the treatment of children of younger age groups, are liquid dosage forms, in particular syrups that may also apply to patients of other age groups.

In the example of U.S. patent N 4282233, 1981, described antihistaminics composition in the form of a syrup, which includes the following ingredients (g/100 ml:

The active ingredient is 0.01

Sucrose - 60,0

Sorbitol - 14,0

Alcohols (propylene glycol, ethanol) is 2.2

Preservatives

(esters of p-oksibenzoynoy acid) - 0,12

Dye (F. D.& C. Yellow No. 6) - 0,0225

Flavor, ml - 0,1

Water - the Rest

As the active substance composition Morkie their dehydrogenated or chlorine substituted analogues, including loratadine. However, the composition has a low concentration of the active substance (0,01%), and the increase of this concentration significantly decreases the stability of the composition during storage (turbidity, sediment) and, accordingly, the shelf life of the drug.

Therefore, still relevant is the problem of creating stable during storage antihistamine drug on the basis of loratidine, which conforms to pharmacopoeial requirements and easy to use.

The technical result obtained by implementing the present invention, is that the new antihistamine composition, made in the form of syrup, sustained over a sufficiently long period (at least 2 years) and meets pharmacopoeial requirements, easy to use and has good organoleptic properties.

This technical result is achieved by the fact that the proposed antihistamine composition in the form of a syrup containing as active ingredient loratadine and as auxiliary substances saccharide, alcohol and water, additionally contains a pharmaceutically acceptable acid in the following ingredients, g/100 ml:

Loratadine 100

The claimed ingredients found experimentally and ensures the stability of the composition and its conformity to the quality requirements of the global Fund XI.

Introduction to composition pharmaceutically acceptable acid along with the use of other excipients in the present limits of unexpectedly improved stability of indicators of the quality of the composition and to improve the content loratidine to 5 g per 100 ml without turbidity syrup and sedimentation and, thus, to increase the shelf life of the composition (over 2 years). In addition, the use of pharmaceutically acceptable acid in the specified quantity makes it possible to avoid a mandatory part preservatives to comply with the composition requirements of the global Fund XI for microbiological purity.

It is preferable to apply a pharmaceutically acceptable acid in an amount to provide a pH of the composition in the range of 2.5-3.5.

Pharmaceutically acceptable acid means that the acid should not significantly increase the toxicity of the active compounds and compositions as a whole. Pharmaceutically acceptable acid comprises tartaric, benzoic, lactobionate, citric, lactic, malic, succinic acid, their preferred wine, citric, succinic and benzoic acid or mixtures thereof in various proportions.

As saccharide use of mono-, di - or polysaccharide, or a mixture of sugars. Examples of such substances are sucrose, glucose, xylitol, sorbitol and other sugar, preferably sucrose.

As alcohol use pharmaceutically acceptable mono-, di - or polynuclear alcohols, for example ethanol, propylene glycol, glycerol or a mixture thereof.

Introduction to composition corrigentov color, taste and smell (dye, flavoring) allows to improve the organoleptic properties of the composition and, thus, the attractiveness of medicines for use in children, especially the younger age group.

As flavoring you can use food flavouring essences, such as lemon, barberries, grapefruit, orange, cherry, strawberry, raspberry, Apple, and others, as well as essential oils.

As the dye, you can use any pharmaceutically acceptable colorant, for example, tropeolin O, acid 2C red, Indigo Carmine, or their mixture.

The optimum content of the flavoring in the composition is from 0.1 mg to 5 g per 100 ml of the dye is from 0.1 mg to 2 g per 100 m of the corresponding effect and the upper economic expediency.

The proposed pharmaceutical composition is in the form of a syrup, which ensures manufacturability subsequent packaging and ease of use.

The claimed medicinal product may be obtained by known standard methods used to obtain syrups.

The purpose of clinical testing of the proposed composition was the study of its tolerability and clinical efficacy for use in children for treatment of allergic rhinitis (seasonal and year-round).

During the research it was determined the dynamics of the main clinical symptoms of allergic rhinitis treatment of the inventive tool, the possibility of side effects and appreciated the ease of use of the drug in the form of a syrup for oral administration.

The study included 20 children suffering from allergic rhinitis, aged 2 to 15 years. Nosological and etiological structure of rhinitis are presented in table 1.

Inclusion criteria children in the research program were:

Age 2 to 15 years.

The presence of rhinitis, existing for more than 3 months.

Proof atopic is Lin B;

the presence of direct relatives in 2 generations on the mother and/or father, who suffered from atopic disease (asthma, allergic rhinitis, conjunctivitis, atopic dermatitis);

positive skin scratch/provocative tests with inhalant allergens;

the coincidence data of history about the exacerbation of rhinitis and impact of "guilty" allergen;

The presence at the time of testing clinical manifestations of rhinitis rinorea (edema of the mucosa) and/or nasal congestion.

The presence Protocol informed consent for the research, signed by at least one of the parents of the child.

Atopic Genesis rhinitis was confirmed in all children with relatives on the mother or father (up to 2nd generation), suffering from this or other atopic disease, moderately or significantly increased levels of total serum immunoglobulin E (more than average age values plus 1 to 2 or more standard deviations), positive skin scratch tests with household and/or pollen allergens. While all children according to the anamnesis showed a clear link between exposure to pricing is zabolevaniya. The original condition of the patients was assessed on day 1 of the study prior to the appointment of a new composition. The attending physician has determined the severity of clinical symptoms of rhinitis in points according to the following scale:

1 point - mild symptoms, not disturbing the patient;

2 points - moderate symptoms, and there are definitely observed. They disturb the patient for some time;

3 points - severe symptoms, pronounced and disturb the patient most of the time.

This assessment is also conducted at 7 and 28 days of treatment. In addition, it was determined the clinical efficacy of the drug on a 6-point grading system:

6 points - excellent clinical effect (no symptoms);

5 points - good clinical effect (clinical manifestations insignificant, there is no need for medication);

4 points - satisfactory clinical effect (there are clinical symptoms, but less pronounced and in patients receiving the drug does not interfere with daily activity;

3 points - weak clinical effect (often symptoms are troubling, but on a background of reception of a preparation does not require the introduction of additional drugs of other groups);

2 points - no effect (agents is Oceania.

The clinical efficacy of a new composition was determined by the attending physician at 7 and 28 days test. In addition to medical evaluation, parents and patients older conducted its own evaluation of the effectiveness of treatment based on subjective feelings. This assessment was performed daily for the entire period of testing. The obtained results were recorded in the diary of self-control of the patient.

The proposed tool was administered depending on vozrasta patient weight:

children from 2 to 12 years: 5 mg (1 teaspoon of syrup) 1 time per day;

children weighing more than 30 kg and above 12 years: 10 mg (2 teaspoonfuls of syrup) 1 time per day.

The drug was used within 28 days of each child.

Interruption of studies, clinical events and cases that would require emergency events associated with the drug, were noted. Dynamics of clinical symptoms of allergic rhinitis treatment offered by the tool are presented in table 2.

The table shows that at 7 and 28 days of treatment number of children with moderate to heavy severe rhinorrhea decreased from 18 to 7 and 2, respectively, with 9 children stated iceskating therapy of 12 children with severe symptom severity had only 1 child.

Quick, to the end of 1 week of treatment, the disappearance of sneezing was observed in most children. Thus, of the 15 patients with severe and moderate the severity of this symptom, it was observed only in 4 to 7 days of therapy and only 1 over 28 days.

To 7 days of treatment in 16 of the 18 children showed slight signs or absence of itching in nose.

Children of all ages eagerly accepted the claimed means. Cases of failure of the drug due to its organoleptic properties were not. Any unpleasant feeling on the part of the mucous membrane of the oral cavity and the gastrointestinal tract when you receive a syrup in children has not occurred.

In the study we can conclude that the drug is in the form of a syrup for oral administration is well tolerated by children. The reduction in severity of symptoms of allergic rhinitis, regardless of its origin, occurs 2-3 days of therapy and continued until the end of 2 to 3 weeks of treatment. On the 28th day of therapy was not observed children with severe manifestations of any symptom of allergic rhinitis. The proposed tool in the form of a syrup for oral administration, it is advisable to recommend for children suffering from both seasonal and year-round is the treatment of the claimed composition in adult patients (20 men) with seasonal and perennial allergic rhinitis showed a high clinical efficacy of the proposed drug in patients with seasonal and perennial allergic rhinitis. In 95% of identified good and excellent results 4 weeks of treatment, and 5% identified a satisfactory treatment outcome.

All patients showed good tolerance of the drug.

Thus, the data of clinical trials of a new composition allow to conclude that the proposed tool has a pronounced therapeutic effect and can be recommended for widespread medical use.

The invention is illustrated by the following examples (see table 3):

Example 1. Mix of 85.1 g colored sugar syrup (prepared from 50.0 g of sucrose, 0.1 g of tropaeolin O and of 35.0 g of water). 10 g of propylene glycol, of 0.44 g of citric acid monohydrate (0.4 g based on 100% acid), 0.1 g of benzoic acid and a solution of 0.1 g loratidine 2.1 g of rectified ethyl alcohol (2.0 g 100% ethanol), and then introduce 0.1 g of aromatic food essences (lemon). Mix until a homogeneous syrupy mass of yellow color, and bring the volume of the syrup with water to 100 ml (pH of the solution is 3.0). The finished syrup is stirred 30 minutes and filtered from solids through a sieve N 61.

The resulting syrup meets pharmaceutical tool (on the. The obtained composition (syrup) satisfy the requirements of the pharmaceutical agent. The results of making syrup is presented in table 3.

1. Antihistamine composition in the form of a syrup comprising as active ingredient loratadine and as auxiliary substances saccharide, alcohol and water, characterized in that it further contains a pharmaceutically acceptable acid in the following ingredients, g/100 ml:

Loratadine is 0.01 to 5.0

Saccharide - 10,0 - 70,0

Alcohol is 0.5 - 45,0

Pharmaceutically acceptable acid To a pH of 2 to 4

Water ml 100

2. Antihistamine composition under item 1, characterized in that it further comprises a flavoring in the amount of 0 to 5.0 g per 100 ml and the dye in the amount of 0 to 2.0 grams per 100 ml.

3. Antihistamine composition on PP.1 and 2, characterized in that as a flavoring food contains aromatic essences, and as a dye, tropeolin O.

4. Antihistamine composition on p. 3, characterized in that its pH is 2.5 to 3.5.

 

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