MULTIPLE-MATRIX MONOLITHIC MOULDED PART FOR THE DIFFUSION OF ACTIVE INGREDIENTS AND METHOD FOR OBTAINING SAME

Abstract

This invention relates to a monolithic molded part comprising multiple cohesive matrices for the simultaneous diffusion of volatile active ingredients, in contact or separately, wherein said multiple matrix is formed by the combination of several simple matrices, characterized in that each of said simple matrices is capable of containing one or more active ingredient(s), each active ingredient having its own release kinetics.

Claims

1. A monolithic molded part comprised of multiple cohesive matrices, having a non-concentric continuous structure, made up of the combination of two to four simple matrices, welded together and obtained by multi-shot molding, wherein each of said single matrices is made of thermoplastic polymer and contains at least one active ingredient different from the active ingredient contained in a neighboring simple matrix, each of which has its own release kinetics, and wherein all of said active ingredients are released simultaneously at substantially different or substantially similar speeds, so that the sum of the quantities of active ingredients released makes it possible to achieve the desired beneficial effects by synergy, wherein said neighboring single matrices are welded together, side by side or face to face, so that the weld ensures the structural continuity of the monolithic molded part, and wherein said weld, which constitutes the interface between neighboring matrices, consists of the mixture, in molten state, of said thermoplastic polymer forming said matrices, wherein said structural continuity is adapted to the migration of a solvent from at least one active ingredient from one simple matrix to another.

2. The monolithic molded part according to claim 1, wherein each of the simple matrices comes from the same thermoplastic polymer family or each of the simple matrices comes from a family of different thermoplastic polymers.

3. (canceled)

4. The monolithic molded part according to claim 2, wherein the solvent, which made the solubilization of the active ingredients possible, is identical from one simple matrix to another or is different from one simple matrix to another.

5. (canceled)

6. The monolithic molded part according to claim 4, wherein the quantity of solvent is different in each of the simple matrices or the quantity of solvent is identical in each of the simple matrices.

7. (canceled)

8. The monolithic molded part according to claim 1, wherein the thermoplastic polymers are biodegradable polymers or not, chosen from the group consisting of polyolefins and their derivatives chosen from polyethylenes (PE), polypropylenes (PP), copolymers of ethylene and vinyl acetate (EVA), ether block amides (EBA), polyvinyl chlorides (PVC), polyamides, copolyamides and their derivatives, polyurethanes and their derivatives, styrenics and their derivatives chosen from among the polystyrene-poly(ethylene-butylene)-polystyrenes (SEBS) copolymers, polystyrene-polyisoprene-polystyrene (SIS) copolymers, polystyrene-polybutadiene-polystyrene (SBS) copolymers, vulcanized thermoplastics, agropolymers and their derivatives chosen from polysaccharides, starch, cellulose and proteins, polyesters and their derivatives, as well as the mixture of all these polymers.

9. The monolithic molded part according to claim 1, wherein the active ingredients have biocidal effects, well-being and cosmetic effects, therapeutic effects, phytosanitary effects and biocontrol effects.

10. The monolithic molded part according to claim 9, wherein the active ingredients are chosen from insecticides, repellents, pheromones, hormones, attractants, perfumes, essential oils, plant extracts, and pharmaceutical active ingredients.

11. The monolithic molded part according to claim 10, wherein the insecticides are chosen from the group consisting of pyrethroids, pyrethrins, carbamates, formamidines, carboxylic esters, phenylpyrazoles, organophosphorus compounds, organohalogenated compounds, neonicotinoids, avermectins and their derivatives, spinosyn, essential oils and their components.

12. The monolithic molded part according to claim 1, wherein it comprises two simple matrices in thermoplastic polymer, the first matrix containing 0.1 to 50% of its weight in an insecticide belonging to the family of pyrethroids while the second simple matrix containing 0.1 to 50% of its weight in active ingredient chosen from pyrethrins, carbamates, formamidines, organophosphorus compounds, organohalogenated compounds, neonicotinoids, phenylpyrazoles, avermectins and their derivatives, spinosyns, perfumes, essential oils, pheromones, hormones, active ingredients with cosmetic effect, pharmaceutical active ingredients, active ingredients with phytosanitary effects or a mixture thereof.

13. The monolithic molded part according to claim 1, wherein one of the matrices contains 0.1 to 50% of its weight in repellent, and in that the other matrix contains 0.1 to 50% of its weight in pheromone, hormone, attractant, perfumes, essential oil, plant extract, active ingredient with cosmetic effect, pharmaceutical active ingredient, active ingredient with phytosanitary effect, or a mixture thereof.

14. The monolithic molded part according to claim 1, wherein it is in the form of a collar, a bracelet, a strap, a plate, a patch, or a medallion.

15. A method for manufacturing a monolithic molded part in cohesive multiple matrices according to claim 1, for the simultaneous diffusion, of volatile active ingredients, by contact ingredients or both, wherein said multiple matrix is made up of the combination of two to four single matrices welded together, wherein a first homogeneous mixture containing a thermoplastic polymer incorporating a first active ingredient is introduced into a first hopper of an injection molding machine to constitute the first simple matrix, and wherein a second homogenous mixture, containing a second thermoplastic polymer which incorporates a second active ingredient is introduced simultaneously into a second hopper of the same injection molding machine to constitute the second simple matrix, and in that the two simple matrices, each of which contains a different active ingredient, are shaped simultaneously by bi-injection of the two homogeneous mixtures.

16. The method according to claim 15, wherein each of the simple matrices is obtained from the same thermoplastic polymer family.

17. The method according to claim 15, wherein each of the simple matrices comes from a different thermoplastic polymer family.

18. The method according to claim 16, wherein a solvent which enabled the active ingredients to solubilize is identical from one simple matrix to another.

19. The method according to claim 16, wherein the solvent which have enabled the active ingredients to solubilize, is different from one simple matrix to another

20. The method according to claim 18, wherein the quantity of the solvent is different from one simple matrix to another.

21. The method according to claim 18, wherein the quantity of the solvent is identical from one simple matrix to another.

22. The method according to claim 17, wherein the melting point of two neighboring matrices results from families of different polymers, wherein the melting points of said polymers are close, with the differential not exceeding 15 C.

Description

EXAMPLE 1

Collar Comprising Active Ingredients Incompatible with Each Other, with Antagonistic Effects

[0054] The manufacture of an antiparasitic collar (ticks, lice, fleas) that regenerates the skin, intended for a pet, is desired. To do this, the following inputs are available: [0055] essential oils of lemongrass, eucalyptus and Mentha pulegium (volatile repellents) [0056] geraniol which, for example, is a component of the essential oil of palmarosa (volatile repellent active) [0057] vitamin F (contact or softening active ingredient or even for regenerating the skin when the collar rubs while wearing) [0058] coconut vegetable oil (emollient, solvent) [0059] EVA granules sold under the EVA PA ALUCIDIA brand [0060] pistachio green dye in granules
Protocol for Preparation by Mixing Repellants with Vitamin F:

[0061] In a 1 L beaker, 200 g of vitamin F, 160 g of Mentha pulegium essential oil, 31.2 g of eucalyptus essential oil, 8 g of lemongrass essential oil and 0.8 g of geraniol are mixed. The mixture is stirred lightly until a homogeneous liquid mixture is obtained.

[0062] For all examples, the percentages by weight are related to the total weight of the final matrix.

[0063] 3519.2 g of EVA are introduced into a cylindrical mixer preheated to 70 C. Then, the above homogeneous liquid mixture is slowly introduced. The mixture is left to be stirred gently until dry granules are obtained. 80 g of pistachio green dye are added and then mixed for 5 minutes. A compound is obtained consisting of EVA polymers loaded with 11.1% by weight of all the active ingredients combined, or 5.5% by weight of vitamin F and 5.6% by weight of repellents.

Shaping by Mono-Injection:

[0064] The above compound is injected into a collar 60 cm long by 1 cm wide and weighing 25 g.

[0065] The collars (C1) thus obtained were analyzed by GPC assay of the active ingredients contained in the matrix at time zero (T0) after injection, then after 7 days of stability at 50 C. in watertight-sealed packaging. The assay results obtained for the various tracers of repellants are listed in Table 1.

TABLE-US-00001 TABLE 1 GPC assay results for collars (C1) containing 5.5% Vitamin F and 5.6% repellents Active ingredient loss (%) Time (days) Cineole Citronellal Pulegone Citronellol Geraniol at T0 12% 12% 11% 7% 6% at T = 7 days at 50 C. 4% 38% 10% 20% 30%

[0066] At T0, the theoretical amount of geraniol, as well as that of each of the tracers of essential oils, should correspond to the amounts of active repellants initially incorporated into the matrix. Consequently, it is estimated that these quantities represent 100% at T0. However, the GPC assay shows that: [0067] at T0 after injection, the collar (C1) has already lost 12%, 12%, 11%, 7% and 6% respectively for cineole, citronellal, citronellol and geraniol, [0068] at T=7 days at 50 C., the loss is accentuated because the collar (C1) has lost 4%, 38%, 10%, 20% and 30% respectively for cineole, citronellal, citronellol and geraniol, or a cumulative loss of 16%, 50%, 21%, 27%, 36% respectively for cineole, citronellal, citronellol and geraniol.

[0069] In parallel, by proceeding according to the same protocol, vitamin F was replaced by coconut oil, in the same proportions, then the corresponding collar compound (C2) was injected. The analyses by GPC assay of the collars (C2) gave the results recorded in Table 2.

TABLE-US-00002 TABLE 2 GPC assay results for collars (C2) containing 5.5% coconut and 5.6% repellents Active ingredient loss (%) Time (days) Cineole Citronellal Pulegone Citronellol Geraniol at T0 0% 0% 0% 3% 0% at T = 7 days at 50 C. 0% 3% 0% 0% 0%

[0070] It is observed that: [0071] at T0 after injection, the collar (C2) retained all the tracers with the exception of citronellol, which shows a loss of 3%, [0072] at T=7 days at 50 C., only the citronellal has been released (3%)

[0073] In conclusion, the mixture of repellants and vitamin F are incompatible with each other when they are incorporated together in this single EVA matrix.

Shaping of the Collars C1 and C2 by Bi-Injection in Compliance with the Invention:

[0074] This time, by means of a bi-injection press, the compounds, leading to obtain to collars (C1) and (C2), were injected simultaneously into a mold provided with a bracelet imprint of dimensions identical to that of Example 1. The pistachio green dye was kept to identify the matrix constituting the collar (C1) while a pearly white dye, used in the same proportions as the pistachio green, is used to identify the matrix constituting the collar (C2).

[0075] It is observed that the release of repellents is no longer negatively impacted by vitamin F; in addition, it is directly diffused upon contact with the animal's skin to induce its cosmetic effect of softening the skin.

EXAMPLE 2

Bracelet Containing Volatile Active Ingredients with Complementary Effect (Expectoration), but with Staggered Release

[0076] Limonene (a component of citrus essential oils) is available, as well as Eucalyptus radiata essential oil, both of which are known for their expectorant properties.

[0077] The protocol for preparing the limonene and eucalyptus essential oil compounds is identical to that of Example 1.

[0078] It has been previously observed that the limonene when released first, makes it possible to thin and clear mucus, while the eucalyptus, released second, ensures a persistence of the expectorant activity while promoting decongestion, ideal in stuffy nose and oily cough. The joint action of the two active ingredients thus increases the expulsion of mucus from the trachea or bronchi by sputum or cough.

[0079] Studies carried out by the inventors have made it possible to prepare the release profiles of limonene as a function of the polymers used, namely PEBA, EVA and the bio-based polyethylene (PE) copolymer. Compounds loaded with 10% limonene were injected in a bracelet. The different limonene release profiles are shown in FIG. 1.

[0080] FIG. 1: release profile at room temperature of limonene incorporated at 10% into different polymer matrices.

[0081] It is observed that the polyether block amide (PEBA) bracelet releases limonene very quickly and in a significant quantity when compared to EVA, which releases gradually, and polyethylene which retains. It is noted that for EVA, after 10 days, the remaining amount of limonene is 42%. It is noted that the PEBA bracelet released 70% of the limonene it contained after 2 days, and was empty after 6 days.

[0082] 10% essential oil of Eucalyptus radiata has been incorporated into an EVA polymer matrix. The corresponding release curve is shown in FIG. 2.

[0083] FIG. 2: release profile at room temperature of Eucalyptus radiata essential oil incorporated at 10% into an EVA matrix

[0084] It is observed that the essential oil of Eucalyptus radiata is released more gradually, so that the amount remaining after 10 days is still greater than 60%.

Shaping of PEBA and EVA Matrices by Bi-Injection in Accordance with the Invention:

[0085] The PEBA polymers loaded with 10% limonene and the EVA polymers loaded with 10% eucalyptus essential oil are shaped into a bracelet by bi-injection as described in Example 1.

[0086] Due to its bi-injection shaping, the PEBA matrix rapidly releases limonene and the EVA matrix gradually releases eucalyptus essential oil, each of which makes it possible to achieve the above-mentioned objective, namely the shock effect, followed by a residual effect, the synergy of the two effects inducing expulsion of mucus by sputum or cough.

EXAMPLE 3

Antiparasitic Collar for Animals Comprising Two Synergistic and Complementary Contact Insecticides Having Different Release Profiles

[0087] Deltamethrin and permethrin are two pyrethroids that are synergistic insecticides (anti-flea and anti-tick). There is also a polyether-based thermoplastic polyurethane (TPU) polymer powder based on polyether (EPAMOULD), as well as a single solvent which is an ethylhexyl diphenyl phosphate (SANTICIZER 141).

[0088] 8% permethrin is solubilized in 22% of SANTICIZER 141 Then, 4% deltamethrin is added, before adding the homogeneous mixture in a single EPAMOULD matrix. The in vitro release profile of the two insecticides over a period of 16 days is shown in FIG. 2.

[0089] FIG. 3: In vitro release profile in the plant oil from the pest control collar containing 8% permethrin and 4% deltamethrin, both solubilized in 22% SANTICIZER 141

[0090] It is observed that after 15 days, the collar has already released 52% of permethrin, against 18% for deltamethrin. However, to effectively repel fleas, it is preferable that the permethrin be released at doses slightly higher than those of the deltamethrin in FIG. 3. Likewise, to repel ticks effectively, it is desirable that the daily released quantities of deltamethrin be slightly greater than those shown in FIG. 3. The objective is therefore to be able to accelerate the release of deltamethrin, and conversely and simultaneously, to slow down that of permethrin, in order to achieve a substantially similar release profile.

Shaping of Two Simple TPU Matrices by Bi-Injection in Compliance with the Invention:

[0091] To achieve the above-mentioned objectives, it seems difficult to obtain a substantially similar release profile of the two insecticides incorporated simultaneously into a single polymer matrix. Therefore, the same amount (8%) of permethrin was solubilized in 5% SANTICIZER 141 prior to incorporation into a EPAMOULD matrix as above, in order to obtain a permethrin compound. In parallel, the same quantity of deltamethrin (4%) solubilized in 22% of SANTICIZER 141 was mixed, prior to incorporation into a EPAMOULD matrix, in order to obtain a deltamethrin compound.

[0092] The two compounds obtained are injected simultaneously in a collar using the bi-injection press as described in Example 1. The in vitro release profile of the two insecticides is shown in FIG. 4.

[0093] FIG. 4: In vitro release profile in plant oil of the antiparasitic collar obtained by bi-injection including a matrix containing 8% of permethrin solubilized in 5% of SANTICIZER 141 and the other matrix containing 4% of deltamethrin dissolved in 22% of SANTICIZER 141.

[0094] FIG. 4 shows that in order to obtain a substantially similar release profile of the two insecticides, it was necessary that one of the two simple EPAMOULD matrices incorporate permethrin solubilized at 5%, while the other incorporates deltamethrin solubilized at 22%. The objective that we have set is therefore achieved by shaping the two simple matrices by bi-injection.