Powder formulation containing insect repellent

Abstract

The present invention relates to a powder formulation comprising at least one insect repellent and magnesium hydroxide carbonate, and to a process for the preparation of the formulation and to the use of the formulation for repelling insects.

Claims

1. A powder formulation comprising (a) at least one insect repellent selected from the group consisting of N,N-diethyl-m-toluamide, ethyl 3-(N-butylacetamino)propionate, 1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine, citronella oil and andiroba oil and (b) magnesium hydroxide carbonate, wherein the magnesium hydroxide carbonate has a bulk density of at most about 200 g/l, the weight ratio of magnesium hydroxide carbonate to insect repellent in the formulations is 2:1 to 1:1 and the formulation comprises 5 to 20% by weight of the at least one insect repellent, based on the total weight of the formulation.

2. The powder formulation according to claim 1, wherein the at least one insect repellent is ethyl 3-(N-butylacetamino)propionate.

3. A powder formulation comprising (a) at least one insect repellent selected from the group consisting of N,N-diethyl-m-toluamide, ethyl 3-(N-butylacetamino)propionate, 1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine, citronella oil and andiroba oil and (b) magnesium hydroxide carbonate, wherein the magnesium hydroxide carbonate has a bulk density of at most about 130 g/l.

4. The powder formulation according to claim 1, which comprises 5 to 10% by weight, based on total weight of formulation, of the at least one insect repellent.

5. The powder formulation according to claim 4, which comprises 10 to 20% by weight, based on the total weight of the formulation, of the at least one insect repellent.

6. The powder formulation according to claim 1, which comprises 5 to 40% by weight, based on the total weight of the formulation, of magnesium hydroxide carbonate.

7. The powder formulation according to claim 6, which comprises 5 to 30% by weight, based on the total weight of the formulation, of magnesium hydroxide carbonate.

8. The powder formulation according to claim 1, wherein the weight ratio of magnesium hydroxide carbonate to insect repellent in the formulation is 2:1 to 1.5:1.

9. The powder formulation according to claim 8, wherein the weight ratio of magnesium hydroxide carbonate to insect repellent in the formulation is 1.5:1 to 1:1.

10. The powder formulation according to claim 1, which furthermore comprises one or more ingredients selected from the group consisting of cereal starch, rice starch, maize starch, modified starch, mica, synthetic mica, boron nitride, titanium dioxide, talc, aluminium oxide, bismuth oxychloride, PMMA, nylon and silica.

11. A process for preparing the powder formulation according to claim 1, comprising mixing the at least one insect repellent with the magnesium hydroxide carbonate and any further ingredients.

12. A process for repelling insects, comprising repelling insects by applying to the skin of a host a powder formulation according to claim 1.

13. The powder formulation according to claim 1, wherein the at least one insect repellent is ethyl N,N-diethyl-m-toluamide.

14. The powder formulation according to claim 1, wherein the at least one insect repellent is 1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine.

15. The powder formulation according to claim 1, wherein the at least one insect repellent is citronella oil.

16. The powder formulation according to claim 1, wherein the at least one insect repellent is andiroba oil.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1a shows the first step of the test for powder distribution in accordance with Example 2: The powder formulations to be tested are applied in small heaps to fine cardboard on a precision balance.

(2) FIG. 1b shows the second step of the test for powder distribution in accordance with Example 2: The heaps were distributed over a distance of 20 cm using the finger under uniform pressure.

(3) The following examples are intended to illustrate the present invention:

EXAMPLES

Example 1: Preparation of the Powder

(4) The individual components of the powder (see Table 2, Table 3 and Table 4) are mixed twice at 8000 rpm for 15 sec. with the aid of a Retsch GM 200 knife mill. The container with the powder is emptied onto a paper between each mixing operation and returned to the mixing container. The insect repellent is added dropwise to the mixing container; mixing is repeated a further three times at 8000 rpm for 15 sec. in each case.

(5) TABLE-US-00001 TABLE 1 Materials and sources of supply: Article Source of Name INCI Number supply IR3535 (ethyl 3-(N- ETHYLBUTYLACETOYL- 111887 Merck butylacetamino)- AMINOPROPIONATE KGaA propionate) Parteck LUB Talc TALC 108070 Merck KGaA Maisita Natural ZEA MAYS (CORN) 9083 Agrana STARCH Covabead PMMA POLYMETHYL Sensient METHACRYLAT Magnesium hydroxyde MAGNESIUM 105829 Merck carbonate heavy (bulk CARBONATE Millipore density >400 g/l) PharMagnesia MC MAGNESIUM 24202010- Lehmann& Type E (bulk density CARBONATE 00 Voss&Co about 120 g/l) Reisita Natural OROZA SATIVA STARCH 9094 Agrana Starke GmbH Parteck LUB MST MAGNESIUMSTEARATE 100663 Merck KGaA Polyethylene Glycol 400 PEG-8 817003 Merck KGaA Arlamol PS15E PPG-15 STEARYL ETHER Croda GmbH Ethanol 96% ALCOHOL 100971 Merck KGaA Polyethylene Glycol PEG-32 817005 Merck 1500 KGaA Tween 20 POLYSORBATE 20 817072 Merck KGaA RonaFlair Mica M MICA 104750 Merck KGaA Magnesia 12 MAGNESIUM 1120000 Magnesia CARBONATE GmbH RonaFlair Soft SYNTHETIC 117756 Merck Sphere FLURPHOLOPITE KGaA RonaFlair ESQ BISMUTH OXYCHLORIDE 117061 Merck KGaA RonaFlair BORON NITRIDE 117778 Merck Boroneige SF-15 KGaA RonaFlair White SYNTHETIC SAPPHIRE 117751 Merck Sapphire KGaA Orgasol 2002 D NAT NYLON-12 Arkema COS

Example 2: Evaluation of the Powder Distribution

(6) Materials used:

(7) MSE4202S-0CE-D0 precision balance from Sartorius AG MSA324S-0CE-DU analytical balance from Sartorius AG 300 g/m.sup.2 photocard from Ludwig Bhr GmbH &Co.KG (Art. No.: 3774690)
Procedure:

(8) The fine cardboard is fixed to the precision balance using double-sided adhesive tape. 30.03 mg of powder are applied to the paper in the form of a small heap. The precise amount used is noted (FIG. 1a).

(9) The index finger is pressed onto the powder heap with a weight of 200 to 250 g (the weight is checked on the precision balance) and moved uniformly over a distance of 20 cm. The result is shown in FIG. 1b. The amount of material that does not remain on the 20 cm distance is transferred quantitatively into a weighing boat and weighed. The amount is noted.

(10) The process is repeated at least three times for each sample.

(11) The quotient of the material remaining on the 20 cm to the material originally employed describes the distribution capacity of the powder and is expressed in % (abrason) (see Table 2 and Table 3). The higher the abrasion, the better the distribution of the formulation on the skin. Formulations having low abrasion cannot be distributed on the skin, since the particles of these formulations stick together.

(12) Formulations A to G are tested. Formulations A, B and C represent classical powder formulations as comparative formulations (Table 2). Formulations according to the invention are formulations D, E, F and G (Table 3).

(13) TABLE-US-00002 TABLE 2 Comparative formulations Material A B C IR 3535 ETHYLBUTYLACETOYLAMINOPROPIONATE 20% 20% 20% Parteck TALC 80% LUB Talc Maisita ZEA MAYS (CORN) STARCH 80% Natural Covabea POLYMETHYL METHACRYLAT 80% PMMA Sum 100.0% 100.0% 100% Pay-off 23.5% 52.7% 45.8% in %

(14) Formulation A represents a standard formulation consisting principally of talc. It has low abrasion and cannot be distributed on the skin. Common substances which are employed in order to make the formulations powdery in order that they can be distributed better on the skin are, for example, starch or PMMA. Formulations B and C exhibit somewhat higher abrasion, but too low in order to allow good distribution on the skin.

(15) TABLE-US-00003 TABLE 3 Material D E F G Parteck LUB TALC 30.00 30.00 48.00 47.00 Talc Magnesium MAGNESIUM 28.00 hydroxide CARBONATE carbonate heavy (bulk density >400 g/l) PharMagnesia MAGNESIUM 28.00 10.00 25.00 MC Type E (bulk CARBONATE density about 120 g/l) Reisita Natural OROZA SATIVA 19.00 19.00 19.00 5.00 STARCH Parteck LUB MAGNESIUMSTEARATE 3.00 3.00 3.00 3.00 MST IR 3535 ETHYLBUTYLACETOYLAMINOPROPIONATE 20.00 20.00 20.00 20.00 Sum 100.00 100.00 100.00 100.0 Abrasion in % 37.2% 87.7% 35.6% 68.8%

(16) Surprisingly, the use of magnesium hydroxide carbonate in the formulations exhibits a significant increase in abrasion.

Example 3: In Vivo Efficacy Study for Determination of the Efficacy of the Powders Against Mosquitoes

(17) Procedure:

(18) i. Suitability Test

(19) a) Mosquitoes: Aedes albopictus, females which have not been fed with blood, 3-5 days after hatching. b) Room temperature: 25 C.-26 C. c) Air humidity: 60%-65% d) Analytical balance: BP110S from Sartorius AG e) Stopwatch: SJ9-2 from Jinque

(20) At least 300 mosquitoes are located in a cage having the dimensions: length=400 mm, width=300 mm and height=300 mm. Test subjects wearing a test glove which leaves 16 cm.sup.2 (4 cm4 cm) of the skin on the back of the hand unprotected place their hand in the cage for 2 min. If more than 30 mosquitoes land on the exposed skin, the test subject and the mosquitoes are regarded as suitable for the test. 4 suitable test subjects (2 male and 2 female) are selected for the test.

(21) ii. Powder Dose: 1.5 mg/cm.sup.2

(22) A total amount of 37.5 mg of the powder is applied to an area of 25 cm.sup.2 (5 cm5 cm).

(23) iii. Performance of the Test:

(24) The test powder is in each case applied uniformly to the back of one hand hand (5 cm5 cm) of each test subject in a dose of 1.5 mg/cm.sup.2. The other hand serves as comparison. Two hours after application of the powder, the test subjects hold the arms in the cage while wearing the test glove, with the area to which the powder has been applied cut out.

(25) It is observed for two minutes whether the mosquitoes land on the exposed areas and suck the blood.

(26) This procedure is repeated every hour until a mosquito lands on the skin during the two minute observation time and sucks blood. The expression in vivo efficacy indicates how long protection against the mosquitoes exists for the respective formulations, i.e. how long it takes until the first mosquito lands on the skin and sucks blood. The value indicated is determined from the average of the determination of the protection time of the four subjects.

(27) iv. Samples Tested:

(28) Formulations E, G, H, I and J according to the invention are tested (see Table 4; the preparation is carried out in accordance with Example 1).

(29) An insect repellent spray of the following recipe serves as a positive control:

(30) TABLE-US-00004 Ingredients INCI [%] A IR3535 ETHYL 20.00 BUTYLACETYLAMINOPROPIONATE Polyethylene PEG-8 5.00 Glycol 400 Arlamol PPG-15 STEARYL ETHER 3.00 PS15E B Ethanol 96% ALCOHOL 35.00 Polyethylene PEG-32 4.00 Glycol 1500 Tween 20 POLYSORBATE 20 1.50 Water AQUA 31.50

(31) Phase A and B are mixed separately. Phase B is slowly added to phase A, and the mixture is stirred until a homogeneous and clear mixture forms (pH (21 C.)=6.70).

(32) Result:

(33) The result of the test is shown in Table 4. An in vivo efficacy of 4.5 hours is obtained for the positive control.

(34) TABLE-US-00005 TABLE 4 Material E G H I J Parteck LUB TALC 30.00 47.00 42.00 57.00 72.00 Talc PharMagnesia MAGNESIUM 28.00 25.00 25.00 20.00 10.00 MC Type E CARBONATE Reisita Natural OROZA SATIVA 19.00 5.00 5.00 5.00 STARCH Parteck LUB MAGNESIUM 3.00 3.00 3.00 3.00 3.00 MST STEARATE RonaFlair MICA 10.00 Mica M IR 3535 ETHYLBUTYL- 20.00 20.00 20.00 15.00 10.00 ACETOYLAMINO- PROPIONATE Sum 100.00 100.00 100.00 100.00 100.00 In vivo 2.3 h 3.8 h 2.8 h 3.5 h 2.5 h efficacy

(35) Formulation G shows that a lower concentration of magnesium hydroxide carbonate and starch is able to extend the efficacy. Formulations I and J show the dependence of the concentration of IR 3535 and the efficacy duration.

Example 4: Formulation Examples

(36) TABLE-US-00006 TABLE 5 Material 1 2 3 4 5 6 7 Parteck LUB TALC 70.00 60.00 85.00 65.00 65.00 50.00 55.00 Talc PharMagnesia MAGNESIUM 20.00 10.00 20.00 MC Type E CARBONATE Magnesia 12 MAGNESIUM 5.00 10.00 15.00 15.00 CARBONATE RonaFlair Soft SYNTHETIC 10.00 Sphere FLURPHOLOPITE RonaFlair BISMUTH 5.00 ESQ OXYCHLORIDE RonaFlair BORON NITRIDE 10.00 Boroneige SF- 15 RonaFlair SYNTHETIC 10.00 White Sapphire SAPPHIRE Orgasol 2002 NYLON-12 5.00 D NAT COS IR 3535 ETHYLBUTYL- 10.00 20.00 10.00 20.00 15.00 20.00 20.00 ACETOYLAMINO- PROPIONATE Sum 100.00 100.00 100.00 100.00 100.00 100.00 100.00