WO1995034200A1

WO1995034200A1 - Biodegradable sustained release composition

Info

Publication number: WO1995034200A1
Application number: PCT/NZ1995/000049
Authority: WO
Inventors: Nigel Paul Maynard; Paul Ivan Sinkovich
Original assignee: Fernz Corporation Limited
Priority date: 1994-06-10
Filing date: 1995-06-02
Publication date: 1995-12-21
Also published as: AU2540495A

Abstract

A sustained release composition for a chemical or biological active ingredient, said composition comprising in substantially a homogeneous form, (A) the active ingredient(s) and (B) a supporting matrix therefor, said matrix comprising: i) at least one wax component, and ii) slightly water soluble waxy substances, and as optional additional component(s) iii) any one or more of a hardener, resin, dye, lubricants, stabilisers, thickeners, binders, chelating agent, antioxidants, and inert fillers (e.g. clays, micro cellulose, etc). The active ingredient is one or more of an acaricide, molluscicide, nematicide, repellent, rodenticide, fungicide, herbicide, bactericide, insecticide, termiticide and/or hormonal composition.

Description

"BIODEGRADABLE SUSTAINED RELEASE COMPOSITION"

TECHNICAL FIELD

The present invention relates to improvements in and/or relating to biodegradable sustained release compositions.

BACKGROUND

Various sustained release compositions are known for allowing an active ingredient over time to enter into a non in vivo environment where such controlled release is important eg. herbicides, insecticides, etc.

RELEVANT REFERENCES

An example of a prior art sustained release composition includes that disclosed in Goodman Fielder Wattie Australian Limited and Incitec Limited's patent specification W091/03940 which discloses a matrix including an amylaceous material together with a synthetic polymer.

DISCLOSURE OF INVENTION

The present invention is to provide an alternative approach which has application in at least a non in vivo environment.

In a first aspect the present invention consists in a sustained release composition for a chemical or biological active ingredient, said composition comprising in substantially a homogeneous form,

(A) the active ingredient(s) and (B) a supporting matrix therefor, said matrix comprising i) at least one wax component, and ϋ) slightly water soluble waxy substances (eg fatty acids or esters/amides of fatty acids, soaps, rosin acids, waxy polyethylene oxide and/or polypropylene oxide type surfactants), and iii) as optional additional component(s) any one or more of a hardener, resin, dye, lubricants, stabilisers, thickeners, binders, chelating agent, antioxidants, and inert fillers (eg clays, micro cellulose, etc).

Preferably the substantially homogeneous form composition has been prepared while said wax component at the very least has been melted.

Another option is to screw extrude as with plastics master batching, wherein the components are blended in the process and may in fact be extruded at or below the melting point.

Examples of active ingredients are: - chlorpyrifos (insecticide) peπnethrin (insecticide) terbuthylazdne (herbicide) wax soluble organophosphates acaricides, molluscicides, nematicides, repellents, rodenticides, fungicides, herbicides, bactericides, insecticides, termiticides and/or homonal composition. Definition of (i) Waxes and (ii) Waxy Substance (i) Waxes: Preferably with melting point between 30 and 150 °C. Generally organic mixtures solid at room temperature, typically properties are water repellency, smooth texture, nontoxicity, insoluble in water, eg: animal (beeswax, spermacti, lanolin, shallac) vegetable (carnauba, candelilla, bayberry, sugar cane) mineral (paraffin, microcrystalline, ozocerite, ceresin, montan) synthetic (chlorinates naphthalenes, ethylenic polymers, polyol ether-esters) (ii) Slightly water soluble (<10% w/w in water at 20C) waxy substances: with melting point between 30 and 150C. eg: fatty acids (saturated and unsaturated) - palmitic, stearic, behenic etc esters or amides of fatty acids metallic soaps of fatty acids - Al, Ca, Zn stearate etc tallow fatty acids - tallow stearic acid, tallow hardened oil etc glycerol fatty acids - glycerol monostearate etc fatty alcohols and esters/amides of fatty alcohols - myrstyl, cetyl, steaiyl etc rosin acids waxy polyethylene oxide and or polypropylene oxide type surfactants dimer acids.

Preferably composition by weight is:

0 - 90% waxes

0 - 90% fatty acids or esters, amides or soaps thereof

0.01 - 20% active ingredient 0 - 30% additives

^♦waxes preferably may be paraffin/microcrystalline/montan/synthetic

^♦fatty acids preferably may be palmitic/stearic/behenic

^♦preferred additives - dyes eg. Bayer Oil Blue 2N fillers - extenders hardeners eg. polyethylene waxes, magnesium stearate lubricants eg. magnesium stearate, calcium stearate stabilisers release modifiers eg. resins - chelating agents eg. EDTA antioxidants eg. butylated hydroxyanisole binders eg. epoxy resins thickeners Preferably the active ingredient is such that unlike a sustained release composition as disclosed in the aforementioned W091/03940, no spent matrix is likely to remain, ie. the whole mix is capable of deterioration in the environment The matrix is biodegradable and degrades in soil over time to leave no undesirable plastic matrices. The rate of the matrix degradation can be controlled by varying rations of ingredients in the matrix. The release of the active ingredient from the matrix into the environment is controlled by two main factors. Firstly, matrix breakdown (ie. physical degradation by dissolution in water of biological breakdown) results in the loss of matrix and concurrent release of ώe active. The rate of matrix degradation can be increased by using a higher proportion of fatty acid in the formulation; if a higher proportion of wax is used in the formulation, the degradation rate of the resulting matrix (and thus the release rate of the active) is decreased.

Secondly, active ingredients can be lost from the matrix by diffusion. For a non water soluble active such as chlorpyrifos, the higher the wax content of the matrix, the faster the active release rate by diffusion. If a large proportion of polar fatty acid is used in the matrix, the release rate of non water soluble actives by diffusion is decreased.

A combination of these two factors (and possibly others) give a particular matrix an overall active release characteristic.

In general it is believed the active release rate is controlled by polarity and volatility at ambient temperatures and pressures.

Preferably a hardener preferably formed of a synthetic wax such as a polyethylene wax or another wax or high melting fatty acid or metal salt of a fatty acid totally miscible in the at least wax component (i) is provided for storage and heat stability.

Preferably the active ingredient is a chemical, ie; is not a microorganism or some alternative.

Preferably the chemical is a organophosphate herbicide or insecticide.

In one form of the present invention, preferably the active ingredient is chlorpyrifos (preferably 10% w/w), chlorpyrifos has a MP of about 45.5 - 46.5°C.

In another aspect the invention consists in a method of forming shaped materials of the aforesaid composition.

Characteristics of the preferred mix are that it is a homogeneous, clear, liquid. Upon cooling to room temperature solidification occurs. The mix can be reheated (65 - 110°C, as required) and reformed without matrix breakdown/decomposition.

When molten/liquid the mix can be poured pumped into moulds, drums, etc. and cooled to form blocks, cylinders, sheets, rods.

Further, when molten the mix can be sprayed into rising cold air to form prills ("shot-tower").

Further, when molten the mix can be forced by pressure through fine needle(s) to produce prills. Prills can be spherical or half spherical depending on whether they are made by cooling in air or by cooling on a flat surface. Another way of forming is by cold extrusion of solid mix eg. Extrude by applying pressure through 1.0mm dye and so formed "spaghetti" is cut at 2.0mm lengths to produce even cylinders.

In a further aspect the present invention may broadly be said to consist in a method of applying over a period of time a chemical or biological active ingredient into an environment (preferably non in vivo), which method comprises applying into [preferably to a desired locus of] the environment a composition as previously defined and allowing the sustained release of the active ingredient therefrom.

Preferably said composition is in the form of pellets, beads, prills, blocks cylinders or other shaped form.

In one form the forming has been by a pressure process, eg. extrusion, modelling or the like, preferably while the at least one wax component (i) is melted. Most preferably a shot forming process without water is used to form the shapes.

In a further aspect the present invention consists in a sustained release composition as previously defined when the composition is in the form of spheres formed by dropping the composition with at least the at least one waxed component of (i) molten, into rising cool air.

In a further aspect the present invention consists in a sustained release composition having substantially no water contamination, said composition being as previously defined and having been shaped without reliance on water, eg. preferably using a shot forming process eg: a melt dropping into rising cool air. Preferably the active ingredient is capable of controlling grass grab, termites, slugs, snails, nematodes or other insects or the like. In other forms the active ingredient can be a bait for slugs, snails or possums or the like and may include a poison. Further the product may contain a herbicide.

The preferred composition is based on a homogeneous solid solution of active ingredient in the matrix formed into prills, cylinders or blocks. The release of the active ingredient is by diffusion and matrix de-composition. The preferred matrix contains wax preferably (especially non-volatile paraffin) and fatty acids (preferably especially stearic acid) or esters or amides or soaps of fatty acids. Optionally the matrix contains hardeners (especially synthetic polyhydric waxes), resins, dyes and lubricants, stabilisers. The preferred active ingredient or ingredients used are completely soluble or miscible in the matrix.

The homogeneous mass is prepared by melting or blending under shear the base matrix so that the active ingredient(s) and any optional additive(s) become uniform in the composition. The mass is then hot or cold formed into desired shape. The present invention preferably provides a slow release matrix which in part relies on ablation of the matrix due to the low by significant solubility of the non paraffinic moiety (typically stearic acid).

Examples of a composition in accordance with the present invention will now be described with reference to Table 1 which shows by way of example sixteen different formulations of a composition in accordance with the present invention.

Table 1

Table 1 (Continued)

Table 1 (Continued)

NB: All weight in g. NOTES:

Formulation #3 shows use of dye

Formulation #1-4 shows use of variable amount of polyethylene hardener Formulation #5 shows use of behenic acid as hardener

Formulation #6 shows use of behenic acid in combination with polyethylene hardener Formulation #7/#8 shows use of different fatty acids, in particular formulation #8 shows use of 3 different fatty acids together. Formulation #9/#10 shows use of different waxes. Formulation #11-#13 shows different ratios of wax to fatty acid ie. #11 30% wax 70% stearic acid ratio #12 50% wax 50% stearic acid ratio #13 100% wax 0% stearic acid ratio These three formulations (#11/#12/#13) were formed into round prills (size range 1.0- 1.6mm) and placed in soil to determine the release characteristics - details below.

Formulation #14 shows use of Magnesium stearate as hardener/lubricant/release rate modifier.

Formulation #15 shows use of another active ingredient (terbuthylazine - herbicide). Formulation #16 shows use of montan wax. Formulation #17 shows use of another active ingredient (permethrin insecticide) suitable for termit barrier protection.

As can be seen in the Table, the ingredients of the matrix are heated and stirred to form a homogeneous solution, which solidifies on cooling. All ingredients are miscible in each other. Typical temperatures required are 65-110°C, depending on matrix, to produce a homogeneous melt. Example 1

This example shows the production of chlorpyrifos containing prills by extrusion of molten matrix. Three different matrix formulations were prepared: # 11 27% wax

62% stearic acid

11% chlorpyrifos ie) 30:70 ratio wax, stearic acid matrix containing 10% chloryrifos

# 12 44% wax

44% stearic acid

12% chlorpyrifos ie) 50:50 ratio wax, stearic acid matrix containing 10% chloryrifos

# 13 87% wax

13% cylorpyrifos ie) 100:0 ration wax, stearic acid matrix containing 10% chlorpyrifos

For each formulation type, spherical prills were prepared by extruding dropwise the molten matrix through a 0.8mm stainless steel syringe needle. Upon cooling to room temperature, the prills were collected and sieved to a size range of 1.0- 1.6mm.

The exact concentration of chlorpyrifos in the prills for each formulation type was determined. This was achieved by dissolving an accurately weighed quantity of the prills in toluene, precipitating the matrix with acetone, and quantitatively analysing the acetone solution for chlorpyrifos content by GC analysis with benzylbenzoate internal standard.

The release characteristics of the prills in soil was determined as follows. A series of polystyrene containers (120mL capacity) with open tops were used. Each container had four drainage holes drilled in the bottom. A layer of glass wool was placed in each pot, followed by 50g of soil (Horotiu sandy loam, shaken through 2mm sieve). The prills under investigation were then added in a layer (0.50g). A further 50g of soil was added on top of the prills and finally a layer of glass wool was placed on the top of each pot. The pots were placed outside, exposed to the environment at ground level. Rainwater was able to freely fall on the pots. At appropriate times, pots were removed from the field trail (in triplicate, ie. three pots for each formulation type). The soil was air dried and the prills retrieved, washed with water, dried and accurately weighed. The prills were then analysed for choloryrifos content by dissolution in toluene, precipitation of the matrix with acetone and quantitative GC analysis for chlorpyrifos using benzylbenzoate internal standard.

Results for the percentage of clyorpyrifos remaining in the prills (average of triplicate results) for times 0,1,2,3,4,8,16,32,64 weeks is plotted in Figure 1. Clearly, variation in the matrix composition has produced different release characteristics for matrices #11, #12 and #13.

At the start of the trial (time 0 weeks) the weight of the prills added to each pot was 0.50g. At time 64 weeks, the weight of the prills that were retrieved from the plots were as follows (results are average of triplicate weighting), Table 2.

Table 2: Weight of retrieved prills at time 0 and 64 weeks

Clearly the matrix in Formulations # 11 and # 12 is degrading in the soil. Example 2

This example shows the production of cylindrical prills by cold extrusion, and the release characteristics of the prills in soil. The prills prepared contained a modifying hardening agent (Luwax) and 10% chlorpyrifos as active ingredient. Formulations prepared were: # 18 45% wax

45% stearic acid 0% Luwax 10% chlorpyrifos

# 19 43% wax 43% stearic acid 3.6% Luwax 10.4% chlorpyrifos

#20 63% wax

27% stearic acid 0% Luwax

10% chlorpyrifos

# 21 26% wax

60% stearic acid 3.4% Luwax

10.6% chlorpyrifos Prills were prepared by extruding the homogeneous matrix through a lmm die under pressure at room temperature. The resulting 'wire' was chopped using a blade into 2mm lengths. This lead to the formation of lmm diameter, 2mm long cylinders. The chlorpyrifos content of the cylindrical prills was determined by GC analysis.

The prills were trailed in soil using the same method as outlined in Example 1.

Results for the percentage of chlorpyrifos remaining in the prills (average of tripUcate results) for times 0,4,8, 16,32 weeks is plotted in Figure 2. Clearly, variation in the matrix composition has produced different release characteristics for matrices #18, #19, #20 & #21. Further it is noted the incorporation of Luwax not only hardens the resulting prills but also reduces the rate at which the chlorpyrifos is released.

Claims

WHATWE CLAIM IS:

1. A sustained release composition for a chemical or biological active ingredient, said composition comprising in substantially a homogeneous form,

(A) the active ingredient(s) and (B) a supporting matrix therefor, said matrix comprising i. at least one wax component, and ii. slightly water soluble waxy substances, and as optional additional components) iii. any one or more of a hardener, resin, dye, lubricants, stabilisers, thickeners, binders, chelating agent, antioxidants, and inert fillers (eg clays, micro cellulose, etc).

2. A composition of claim 1 wherein each of B(i) and B(ii) components has a melting point in the range 30° to 150°C.

3. A composition of claim 1 or 2 wherein component(s) B(i) are selected from the group of animal, vegetable, mineral and synthetic waxes.

4. A composition of any one of the preceding claims wherein components) B(i) is or includes at least one animal wax selected from the group comprising beeswax, spermatic, lanolin and shallac.

5. A composition of any one of the preceding claims wherein component(s) B(ii) is or includes at least one vegetable wax selected from the group comprising carnauba, candelilla, bayberry and sugar cane.

6. A composition of any one of the preceding claims wherein component(s) B(ii) is or includes at least one mineral wax selected from the group comprising paraffin, microcrystalline, ozocerite, ceresin and montan.

7. A composition of any one of the preceding claims wherein component(s) B(ii) is or includes at least one synthetic wax selected from the group comprising chlorinates naphthalenes, ethylenic polymers and polyol ether-esters.

8. A composition as claimed in any one of the preceding claims wherein said B(ii) substance have a solubility of less than 10% weight weight in water at 20°C.

9. A composition of any one of the preceding claims wherein B(ii) components) is selected from the group consisting of fatty acids, esters/amides/soaps of fatty acids, fatty alcohols, esters/amides of fatty alcohols, rosin acids, dimer acids, waxy polyethylene oxide and/or polypropylene oxide type surfactants.

10. A composition as claimed in claim 9 wherein component(s) B(ii) is at least one component selected from the group comprising fatty acids, esters/amides of fatty acids, rosin acids, waxy polyethylene oxide and/or polypropylene oxide type surfactants.

11. A composition of any one of the preceding claims wherein the substantially homogeneous form composition has been prepared while said wax component at the very least has been melted.

12. A composition of any one of the preceding claims wherein the components are blended and extruded at or below the melting point of components B(i) and (Bii).

13. A composition of any one of the preceding claims wherein the active ingredient (A) is one or more of an acaricide, molluscicide, nematicide, repellent, rodenticide, fungicide, herbicide, bactericide, insecticide, termiticide and/or homonal composition.

14. A composition of any one of the preceding claims wherein the active ingredient (A) is one or more of chlorpyrifos (insecticide), permethrin (insecticide) and/or terbuthylazine

(herbicide).

15. A composition of any one of the preceding claims comprising by weight:

0 - 90% waxes

0 - 90% fatty acids and/or esters, amides and/or soaps thereof 0.01 - 20% active ingredient

0 - 30% additives

16. A composition of any one of the preceding claims wherein B(i) components) is or includes one or more of paraffin, microcrystalline, montan and/or synthetic waxes.

17. A composition of any one of the preceding claims wherein B(ii) components) is or includes one or more of the fatty acids palmitic, stearic and/or behenic.

18. A composition of any one of the preceding claims wherein B(iii) components) selected from one or more of the preferred additives dyes - filler - extenders hardeners lubricants stabilisers release modifiers - chelating agents antioxidants binders, and thickeners is present.

19. A composition of any one of the preceding claims when substantially as hereinbefore described with reference to Table 1.

20. A composition of any one of the preceding claims when in a shaped form.

21. A method of applying over a period of time a chemical or biological active ingredient into an environment (preferably non in vivo), which method comprises applying into the environment a composition as claimed in any one of the preceding claims and allowing the sustained release of the active ingredient therefrom.

22. A method of claim 21 wherein said composition is in the form of pellets, beads, prills, blocks cylinders or other shaped form.

23. A sustained release composition as claimed in any one of claims 1 to 20 when the composition is in the form of spheres formed by dropping the composition with at least the at least one waxed component of (i) molten into rising cool air.

24. A sustained release composition having substantially no water contamination, said composition being as claimed in any one of claims 1 to 20 and 23 and having been shaped without reliance on water.

25. A slow release matrix for a chemical active ingredient which in part relies on ablation of the matrix due to a low but significant solubility of a non paraffinic moiety of a composition as claimed in any one of claims 1 to 20.

26. A matrix of claim 25 wherein said non paraffinic moiety is stearic acid.