COMPOSITION FOR THE PREVENTION AND/OR TREATMENT OF ALLERGY SYMPTOMS

Abstract

The present invention relates to a pharmaceutical composition or a food supplement composition and use thereof in the prevention and/or treatment of allergy symptoms, preferably allergic rhinitis and/or allergic conjunctivitis symptoms. In particular, the composition according to the invention comprises at least one slow release component comprising quercetin and at least one fast release component comprising an extract from Perilla frutescens or a constituent thereof selected from luteolin, rosmarinic acid, apigenin, catechina, ferulic acid, caffeic acid or mixtures thereof, The invention further comprises the use of the composition in the prevention and/or treatment of allergy symptoms, preferably allergic rhinitis and/or allergic conjunctivitis symptoms.

Claims

1. Composition comprising: at least one slow release component comprising quercetin; and at least one fast release component comprising an extract from Perilla frutescens or a constituent thereof selected from luteolin, rosmarinic acid, apigenin, catechin, ferulic acid, caffeic acid or mixture thereof.

2. Composition according to claim 1, wherein quercetin is in the form of its glucosides and/or its salts.

3. Composition according to claim 1, wherein quercetin derives from Sophora Japonica or Dimorphandra mollis, preferably Sophora Japonica.

4. Composition according to claim 1, wherein quercetin is in a percentage from 1% to 70%, where each % is referred to the total weight of the composition.

5. Composition according to claim 1, wherein quercetin is in the composition in an amount from 50 mg to 1000 mg.

6. Composition according to claim 1, wherein the perilla frutescens extract is water-soluble.

7. Composition according to claim 1, wherein the perilla frutescens extract derives from leafs or seeds of Perilla frutescens.

8. Composition according to claim 1, wherein the perilla frutescens extract is in a percentage from 1% to 50%, where each % is referred to the total weight of the composition.

9. Composition according to claim 1 comprising an amount of the perilla frutescens extract from 5 mg to 500 mg.

10. Composition according to claim 1, wherein the slow release component comprises a fat-soluble compound selected from fatty acids C.sub.8-C.sub.24, glycerides, fatty alcohol C.sub.8-C.sub.24, and mixture thereof.

11. Composition according to claim 1, wherein the slow release component comprises at least one fat-soluble vitamin and/or at least one surfactant.

12. Composition according to claim 1, wherein the slow release component further comprises colecalciferol.

13. Composition according to claim 12, comprising an amount of colecalciferol from 1 μg to 10 μg.

14. Composition according to claim 1, wherein the fast release component comprises disruptive agents, excipients diluents, adjuvants, lubricants, sweeteners or mixture thereof.

15. Composition according to claim 1 in the form of tablets, minitablets, capsules, or granulate.

16. Method of preventing and/or treating allergy symptoms in a subject in need thereof with a composition as defined in claim 1, said method comprising: administering to said subject an effective amount of said composition, wherein said allergy symptoms comprise allergic rhinitis and/or allergic conjunctivitis symptoms.

17. Food supplement comprising the composition as defined in claim 1.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0056] The present invention will be now described, for illustrative, but not limitative purposes, according to its preferred embodiments, with particular reference to the figures of the enclosed drawings, wherein:

[0057] FIG. 1 shows data related to total average reduction of symptoms (±DS), obtained by comparing the severity of symptoms found at the initial and final visit after the administration of a composition according to the invention, as reported in the experimentation of example 1;

[0058] FIG. 2 shows data related to the reduction of the total score of symptoms for each patient obtained by comparing the results obtained at the initial and final visit after the administration of a composition according to the invention, as reported in the experimentation of example 1;

[0059] FIG. 3 shows data related to the reduction of the different symptoms individually considered, by comparing the results obtained at the initial and final visit after the administration of a composition according to the invention, as reported in the experimentation of example 1.

EXAMPLE 1

[0060] A clinical trial was carried out in order to demonstrate the effectiveness of the composition of the invention in reducing the nasal and ocular symptoms in the allergic subjects involved. Similarly, the effect of the intake of the composition on the consumption of other anti-allergy drugs was assessed.

[0061] The subjects involved in the trial were 23 adult, namely 16 women with an average age of 44 years old and 7 men, with an average age of 46 years old. All the subjects had a story of allergic rhinitis and/or conjunctivitis for at least one year and were positive to the prick test or RAST for Parietaria officinalis pollen. The subjects, at the moment of the involvement in the trial, have all the nasal and/or ocular symptoms of the seasonal allergic rhinitis.

[0062] Subjects suffering from bacterial or viral infections of the upper or lower respiratory tracts, paranasal sinuses or ear, within the thirty days before their involvement in the trial, were excluded from the trial. Similarly, pregnant women or women during nursing or women that intended to start a pregnancy within the period of the trial, were excluded.

[0063] The experimentation was carried out according to a open clinical trial by administering the composition of the invention, as reported in the example 2, in the form of tablet, twice daily (morning and evening), during or after meals, for 30 consecutive days. After having carried out the two daily administrations, patients reported symptoms by filling in an assessment sheet which included six parameters, namely sneezing, Rinorrea, nasal obstruction, ocular itching, lachrymation, congestion of conjunctiva, according to a numeric score ranging from 0 to 3 (rating scale: 0=no episode; 1=1-5 episodes/day, 2=6-10 episodes/days; 3=≧11 episodes/day). Patients were subjected to a total of two clinical visits (initial visit, before starting the trial and final visit, at the end of the trial) carried out one month away (the treatment duration was of about 30 days). Particularly, during the first visit, the following information for each patient were collected: demographic details, clinical history, with particular reference to the onset of the ongoing allergic pathology, the assessment of nasal and/or ocular symptoms, the assessment of the consumption of anti-allergic drugs, the inclusion or exclusion criteria, concomitant intake of other drugs, with possible side effects, as well as the informed consent request. Instead, during the second visit the following information were assessed: the assessment of the severity of the nasal and/or ocular symptoms reached during the period of drug administration, the assessment of the consumption of anti-allergic drugs and possible side effects reached during the administration period of the composition according to the invention. Simultaneously, it was carried out the monitoring of Parietaria Officinalis allergens into the atmosphere of Imperia district, where the trial was carried out, for the entire duration of the trial.

[0064] Results

[0065] The comparison between the scores obtained from the two visits (initial and final) simultaneously shows an average reduction of about 70% for the symptomatological scores and of about 73% as far as the consumption of other anti-allergic drugs is concerned.

[0066] In FIGS. 1 and 3 are reported, respectively, the data related to the total average reduction of symptoms and the reduction of the several symptoms individually considered, always comparing the results obtained in the first and second visit.

[0067] Particularly, by comparing the results obtained for both sexes (see Table 1) it is evident the same trend, with results slightly better for women (less 72% of symptoms and less 76% of consumption of other drugs) with respect to the results obtained for men (less 68% of symptoms and less 67% of consumption of other drugs).

TABLE-US-00001 TABLE 1 (average values) Women (n = 16) Men (n = 7) Age (years) 44 46 Symptomps 72% 68% reduction Consumption 76% 67% reduction of anti- allergic drugs

[0068] None of the subjects had relevant side effect and none of the subjects interrupted the treatment before of the thirty days expected.

[0069] In the period considered, the level of Parietaria allergens into the atmosphere was always high, as weekly monitored by reading of Urticaceae levels in the regional pollen bulletin, station of Imperia, published on-line on the ARPAL (REGIONAL AGENCY FOR THE LIGURIAN ENVIRONMENT PROTECTION) website.

EXAMPLE 2

[0070] Below an example of the preparation of a composition according to the invention, in the form of bilayer tablet, namely comprising both the fast release component and the slow release component in two separated layers, is reported.

[0071] The amounts of the ingredients used in the following preparation process are indicated in Table 2, reported below.

[0072] According to the process carried out, quercetin and vitamin D.sub.3 were mixed with fused stearin obtaining a granulate cooled at room temperature (20-25° C.). After cooling, the granulate was made uniform by means of a sieve.

[0073] Microcrystalline cellulose, silicon dioxide and magnesium stearate have been added to the granulate and the whole was mixed until obtaining an homogeneous granulate. Said preparation represents the slow release component (or layer).

[0074] The ingredients of the fast release component (or layer), namely dry extract of perilla seeds, cross-linked sodium carboxymethylcellulose (cross-linked CMC Na), maltodextrin, microcrystalline cellulose, silicon dioxide and magnesium stearate, were mixed until obtaining an homogeneous mixture.

[0075] The granulate (slow release component) and the mixture (fast release component or layer) separately feed the loading stations of a tableting machine suitable to form bilayer tablets.

[0076] Tablets with a 9 mm diameter were obtained, formed by two distinct layers, characterized by a different dissolution profile. Tablets were then protected by a filming layer consisting of methylcellulose, talc and carnauba wax.

TABLE-US-00002 TABLE 2 Ingredient Amount Slow release component Quercetin 150.0 mg Vitamin D3 5.0 μg Vegetable stearin 35.0 mg Microcrystalline cellulose 30.0 mg Silicon dioxide 1.5 mg Mg stearate 2.0 mg Fast release component Perilla seeds 80.0 mg (hydrosoluble dry extract) Cross-linked CMC Na 3.0 mg Maltodextrin 40.0 mg Microcrystalline cellulose 18.5 mg Silicom dioxide 0.8 mg Magnesium stearate 1.8 mg Filming component Ethyl cellulose 2.0 mg Talc 1.0 mg Carnauba wax 0.2 mg

[0077] Tablets thus obtained were subjected to a disintegration test in water, at the temperature of 37° C., according to what is described in the European Pharmacopoeia (5.sup.th edition), “2.9.1. “Disintegration of tablets and capsules”, pag. 225-227. The first layer, consisting of the fast release component, disintegrated in less than 2 minutes, instead the second layer, consisting of the slow release component, disintegrated in about 3 hours and 50 minutes.

EXAMPLE 3

[0078] Below an example of the preparation of a composition according to the invention, in the form of monolayer tablet, is reported.

[0079] The amounts of the ingredients used in the following preparation process are indicated in Table 3, reported below.

[0080] According to the process carried out, quercetin, vitamin D.sub.3 and microcrystalline cellulose were mixed and kneaded with fused glyceryl behenate. After cooling, the granulate were made uniform by means of a sieve.

[0081] All the other ingredients were added to the granulate. After mixing, tablets of a weight of 450 mg were manufactured. Tablets then were filmed with a filming layer consisting of methylcellulose, talc and carnauba wax.

TABLE-US-00003 TABLE 3 Ingredient Amount Quercetin 150.0 mg Perilla seeds 80.0 mg (hydrosoluble dry extract) Vitamin D3 5.0 μg Glyceryl behenate 50.0 mg Maltodextrin 80.0 mg Microcrystalline cellulose 70.0 mg Sodium starch glycolate 13.0 mg Stearic acid 4.6 mg Filming component Ethylcellulose 2.0 mg Talc 1.0 mg Carnauba wax 0.2 mg

EXAMPLE 4

[0082] Below an example of the preparation of a composition according to the invention, in the form of sachet, is reported.

[0083] The amounts of the ingredients used in the following preparation process are indicated in Table 4, reported below.

[0084] According to the process carried out, quercetin, vitamin D.sub.3 and maltodextrin were mixed and kneaded with polyoxyethylenglicol esters (Gelucire 44/14) (melted) obtaining a granulate. After cooling, the granulate was made uniform by means of a sieve.

[0085] All the other components were added to the granulate, mixed until obtaining an homogeneous preparation. The mixture was dosed in sachets of a weight of 3 g/sachet.

TABLE-US-00004 TABLE 4 Ingredient Amounts Quercetin 200.0 mg Perilla seeds 100.0 mg (hydrosoluble dry extract) Vitamin D3 5.0 μg Gelucire 44/14 200.0 mg Sucroester P1570 100.0 mg Maltodextrin 500.0 mg Mannite 2000.0 mg Fructose 1832.6 mg Sodium saccharin 15.0 mg Aroma 50.0 mg

EXAMPLE 5

[0086] Below an example of the preparation of a composition according to the invention, in the form of capsule, is reported.

[0087] The amounts of the ingredients used in the following preparation process are indicated in Table 5, reported below.

[0088] According to the process carried out, quercetin, vitamin D3 were mixed with microcrystalline cellulose and kneaded with melted hydrogenated fatty acids. After cooling, the granulate was made uniform by means of a sieve. Maltodextrin, silicon dioxide and magnesium stearate were added to the calibrated granulate, with subsequent mixing until obtaining a homogeneous preparation. The granulate was compressed by lenticular punches of 2 mm diameter obtaining minitablets of about 20 mg by weight (slow release minitablets).

[0089] The components of the fast release minitablets (Perilla seeds dry extract, maltodextrin, HPC, silicon dioxide, magnesium stearate) were mixed until obtaining an homogeneous preparation. The mixture was compressed by lenticular punches of 2 mm diameter obtaining minitablets of about 20 mg by weight (fast release minitablets).

[0090] About 15 slow release minitablets and about 8 fast release minitablets were dosed, by a suitable automatic encapsulator, in capsules of HPMC (hydroxypropylmethylcellulose) format 1.

TABLE-US-00005 TABLE 5 Ingredient Amount Slow release minitablets Quercetin 150.0 mg Vitamin D3 5.0 μg Hydrogenated fatty acids 40.0 mg Microcrystalline cellulose 30.0 mg Maltodextrin 71.5 mg Silicon dioxide 1.5 mg Mg stearate 2.0 mg Fast release minitablets Perilla seeds 80.0 mg (hydrosoluble dry extract) Maltodextrin 61.4 mg Hydroxypropylcellulose 10.0 mg Sodium Croscarmellose 6.0 mg Silicon dioxide 0.8 mg Magnesium stearate 1.8 mg

EXAMPLE 6

[0091] Below it is reported a pilot micro-study carried out on a patient with known allergy to birch pollens and strong symptomatology both nasal and ocular, which normally needs of topic pharmacological treatment (nasal-spray and/or eye drops) and/or systemic. Following the weekly pollen calendar, the product according to Example 2 was administered to the patient with the increase of the pollen count, even under the limits which cause symptomatology. The patient never had any symptoms nor took any type of anti-allergic drug as deduced by the daily calendar.