DERMATOLOGICAL COLLAR FOR NON-HUMAN ANIMALS

Abstract

The present invention relates to a collar for non-human animals, preferably for companion animals, comprising a polymeric matrix and a lipid extract comprising sphingomyelins. It also refers to the collar for use as a medicine, particularly for use as an adjuvant and for use in the treatment or prevention of atopic dermatitis or allergic dermatitis, as well as in restoring the integrity of the skin during or after an atopic dermatitis or an allergic dermatitis, increasing the hydration and flexibility of the skin, facilitating skin regeneration or reducing itching of the skin.

Claims

1. A collar for non-human animals comprising a polymeric matrix and a lipid extract, wherein the lipid extract comprises sphingomyelins.

2. The collar according to claim 1, wherein the polymeric matrix is thermoplastic polyurethane.

3. The collar according to claim 1, wherein the lipid extract comprises at least 30% by weight of sphingomyelins with respect to the total weight of the lipid extract.

4. The collar according to claim 3, wherein the lipid extract comprises between 30% and 70% by weight of sphingomyelins with respect to the total weight of the lipid extract, between 1% and 15% by weight of ceramides with respect to the total weight of the lipid extract, less than 0.5% by weight of sulphatides with respect to the total weight of the lipid extract, less than 0.5% by weight of gangliosides with respect to the total weight of the lipid extract, between 20% and 58% by weight of phospholipids with respect to the total weight of the lipid extract, and between 0.5% and 10% by weight of neutral lipids with respect to the total weight of the lipid extract, and the sum of the percentages of the lipid extract components is equal to 100%.

5. The collar according to claim 4, wherein the lipid extract comprises between 45% and 65% by weight of sphingomyelins with respect to the total weight of the lipid extract, between 2% and 6% by weight of ceramides with respect to the total weight of the lipid extract, less than 0.2% by weight of sulphatides with respect to the total weight of the lipid extract, less than 0.2% by weight of gangliosides with respect to the total weight of the lipid extract, between 25% and 45% by weight of phospholipids with respect to the total weight of the lipid extract, and between 0.5% and 4.5% by weight of neutral lipids with respect to the total weight of the lipid extract, and the sum of the percentages of the lipid extract components is equal to 100%.

6. The collar according to claim 5, wherein the lipid extract comprises between 50% and 59% by weight of sphingomyelins with respect to the total weight of the lipid extract, between 3.5% and 5.2% by weight of ceramides with respect to the total weight of the lipid extract, less than 0.05% by weight of sulphatides with respect to the total weight of the lipid extract, less than 0.05% by weight of gangliosides with respect to the total weight of the lipid extract, between 32% and 44% by weight of phospholipids with respect to the total weight of the lipid extract, and between 1% and 3% by weight of neutral lipids with respect to the total weight of the lipid extract, and the sum of the percentages of the lipid extract components is equal to 100%.

7. The collar according to claim 1, wherein the lipid extract is bovine or porcine.

8. The collar according to claim 7, wherein the lipid extract is from bovine or porcine trachea.

9. The collar according to claim 1, comprising from 2% to 5% by weight of the lipid extract with respect to the weight of the collar.

10. The collar according to claim 9, comprising 2.5% by weight of the lipid extract with respect to the weight of the collar.

11. A medicine for non-human animals comprising the collar according to claim 1.

12. An adjuvant comprising the collar according to claim 1.

13. A method for treating or preventing atopic dermatitis or allergic dermatitis in a non-human animal in need thereof, which comprises putting on the collar described in claim 1 on the animal's neck.

14. A method for restoring the integrity of the skin during or after atopic dermatitis or allergic dermatitis, increasing the hydration and flexibility of the skin, reducing itching of the skin or facilitating skin regeneration in a non-human animal in need thereof, which comprises putting on the collar described in claim 1 on the animal's neck.

15. The method according to claim 13, characterised in that the collar is kept on the animal's neck for eight weeks so that the lipid extract is released onto the body of the non-human animal.

16. The method according to claim 14, characterised in that the collar is kept on the animal's neck for eight weeks so that the lipid extract is released onto the body of the non-human animal.

17. A method for preparing the collar described in claim 1, comprising the following steps: 1) heating the polymeric matrix; 2) adding to the polymeric matrix of step 1) a mixture comprising a plasticizer and a stabilizer; 3) cooling the mixture of step 2); 4) adding the lipid extract, and 5) moulding the mixture resulting from step 4) into a collar shape.

18. The method according to claim 17, wherein the polymeric matrix is thermoplastic polyurethane.

19. The method according to claim 17, wherein the plasticizer is ethylhexyl diphenyl phosphate and the stabilizer is a mixture of C7-9-alkyl 3-(3,5-di-trans-butyl-4-hydroxyphenyl)propionate, isomers of 2-(2H-benzotriazol-2-yl)-4-methyl-(n)-dodecylphenol, bis(1,2,2,6,6-pentamethyl-4-piperidyl) sebacate and methyl 1,2,2,6,6-pentamethyl-4-piperidyl sebacate.

20. The method according to claim 17, wherein the polymeric matrix and the lipid extract are present in the collar in a weight ratio of polymeric matrix to lipid extract comprised between 30:1 and 29:1

Description

BRIEF DESCRIPTION OF THE FIGURES

[0070] FIG. 1 shows the percentage of release of the lipid extract over time, in days, in an in vitro study.

[0071] FIG. 2 shows the mean score of the lesions using the CADESI, at the beginning, and at four and eight weeks of treatment.

[0072] FIG. 3 shows the mean score of the degree of itching using the PICAD, at the beginning, and at four and eight weeks of treatment.

[0073] FIG. 4 shows the mean score of the degree of itching by the owner of the dog using the PVAS index, at the beginning, and at one week and two weeks of treatment.

EXAMPLES

[0074] The following examples are for illustrative purposes and do not represent a limitation on the scope of the present invention.

Example 1: Preparation of a 35 cm Long Collar

[0075] 9.76 g of thermoplastic polyurethane (TPU) were introduced in a reactor preheated to a temperature of 90° C.-95° C. and under stirring. Once the polymer reached said temperature, 2.62 g of the ethylhexyl diphenyl phosphate plasticizer, 0.0655 g of a mixture of the stabilizers C7-9-alkyl 3-(3,5-di-trans-butyl-4-hydroxyphenyl)propionate, isomers of 2-(2H-benzotriazol-2-yl)-4-methyl-(n)-dodecylphenol, bis(1,2,2,6,6-pentamethyl-4-piperidyl) sebacate and methyl 1,2,2,6,6-pentamethyl-4-piperidyl sebacate and 0.1965 g of lavender oil were gradually added. Stirring was continued until said mixture was completely incorporated into the polymer. Next, the resulting mixture was cooled to room temperature, maintaining stirring at all times. Subsequently, 0.33 g of lipid extract were added (see composition in Table 4), and the resulting mixture was stained (with black iron oxide) and homogenised. The reactor was drained and finally the mixture obtained was shaped in a mould by injection. The collar obtained contained 2.5% lipid extract by weight with respect to the weight of the collar.

Example 2: Preparation of a 75 cm Long Collar

[0076] The same methodology explained for the 35 cm collar was repeated, but in this case 19.67 g of thermoplastic polyurethane, 0.66 g of lipid extract, 5.28 g of the ethylhexyl diphenyl phosphate plasticizer, 0.132 g of a mixture of the stabilizers C7-9-alkyl 3-(3,5-di-trans-butyl-4-hydroxyphenyl)propionate, isomers of 2-(2H-benzotriazol-2-yl)-4-methyl-(n)-dodecylphenol, bis(1,2,2,6,6-pentamethyl-4-piperidyl) sebacate and methyl 1,2,2,6,6-pentamethyl-4-piperidyl sebacate and 0.396 g of lavender oil were used. The collar obtained contained 2.5% lipid extract by weight with respect to the weight of the collar.

Example 3: In Vitro Study of the Release of the Lipid Extract

[0077] The purpose of this study was to evaluate in vitro how much and for how long the lipid extract was released from the collar in a fatty medium, considered representative of the sebum from the skin of domestic animals.

Materials and Methods

[0078] This study was conducted with a laboratory batch of three collars, obtained according to Example 1, containing 2.5% by weight of lipid extract.

[0079] The three collars were fragmented, and the pieces of each collar were immersed in a fatty medium consisting of a mixture of triglycerides and shaken with a magnetic stirrer. A piece of each collar was taken at each moment to be analysed: at the beginning, and after 8, 15 and 22 days. At each of these points in time, the same laboratory analysis method was carried out: quantification of methyl palmitate (component of the lipid extract) by gas chromatography. This made it possible to determine the remaining content of lipid extract in each of the three collars, and then calculate the average of the three collars. The percentage of release was determined with this value.

Results

[0080] The results obtained are summarised in Table 5 below:

TABLE-US-00005 TABLE 5 RESULTS Percentage Percentage of lipid of extract release of remaining the lipid in the collar extract Time (average of (average of (days) three collars) three collars) 0 2.56 0 8 2.15 16 15 2.13 17 22 2.01 21

[0081] FIG. 1 also shows the percentage of release of the lipid extract over time.

[0082] As can be observed, at 22 days, the percentage of release of the lipid extract was 21% in the mixture of triglycerides. Thus, the study showed good release kinetics of the lipid extract in a fatty medium.

Example 4: In Vivo Study of Efficacy and Safety in Dogs with Atopic Dermatitis

[0083] The purpose of this study was to determine the effects of the application of the collar in the management of canine patients with atopic dermatitis, assessing the safety of the application of the product and the effects on the extent and severity of the lesions, as well as on itching.

Materials and Methods

[0084] This study included 12 dogs of different breeds, gender and ages with a confirmed diagnosis of non-seasonal atopic dermatitis and without other significant concomitant diseases, to which the collar of Example 1 or of Example 2 was fitted on the neck, depending on the size of the dog.

[0085] The total duration of treatment and follow-up from the start of treatment was 8 weeks. Veterinarian control visits were conducted at the start of treatment (0 weeks) and then at 4 and 8 weeks using 2 scores (Canine Atopic Dermatitis Extent and Severity Index—CADESI)-4; and Pruritus Index for Canine Atopic Dermatitis—PICAD), in addition to weekly evaluations of itching performed by the owner (Pruritus Visual Analog Scale—PVAS).

[0086] The CADESI made it possible to score various lesions (erythema, lichenification, and alopecia/excoriation) on different body regions (pinna, armpits, front and hind legs, elbow folds, carpal and metacarpal pads, flanks, inguinal regions, abdomen, perineal region and proximal ventral portion of the tail).

[0087] The PICAD made it possible to score itching on various body regions, observing the frequency and intensity of: scratching/shaking the ears, scratching/rubbing the head, scratching/rubbing/licking the trunk or armpits, scratching/rubbing/licking the ventral abdomen, licking/biting the front feet, licking/biting the hind feet, licking/biting the legs and rubbing/licking/biting the anogenital region.

[0088] The PVAS index made it possible to score the itching observed by the dog's owner, who noted the degree of itching shown by the pet once a week, on a scale from 0 to 10, where 0 was no itching and 10 was unbearable itching.

Results:

[0089] The application of the collar for 8 weeks was found to be safe and did not lead to the appearance of associated side effects.

[0090] A significant decrease from 0 to 4 weeks (43%; p<0.05), in addition to a significant decrease from 0 to 8 weeks (48.6%; p<0.05) was observed in the CADESI (see FIG. 2).

[0091] A significant decrease from 0 to 4 weeks (52.3%; p<0.05), and a significant decrease from 0 to 8 weeks (43.2%; p<0.05) was observed in the PICAD (see FIG. 3).

[0092] A significant decrease (p<0.05) from 0 to 2 weeks (25.8%) and from 1 to 2 weeks (20.6%) was observed in the PVAS index (see FIG. 4).