GB1572718A – Methods for reducing the doses of biologically active substances while maintaining their biological effects
– Google Patents
GB1572718A – Methods for reducing the doses of biologically active substances while maintaining their biological effects
– Google Patents
Methods for reducing the doses of biologically active substances while maintaining their biological effects
Download PDF
Info
Publication number
GB1572718A
GB1572718A
GB48278/76A
GB4827876A
GB1572718A
GB 1572718 A
GB1572718 A
GB 1572718A
GB 48278/76 A
GB48278/76 A
GB 48278/76A
GB 4827876 A
GB4827876 A
GB 4827876A
GB 1572718 A
GB1572718 A
GB 1572718A
Authority
GB
United Kingdom
Prior art keywords
carrier
biologically active
active substance
composition
agents
Prior art date
1976-06-29
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB48278/76A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kockums Chemical AB and Co KG
Original Assignee
Kockums Chemical AB and Co KG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
1976-06-29
Filing date
1976-11-19
Publication date
1980-07-30
1976-11-19
Application filed by Kockums Chemical AB and Co KG
filed
Critical
Kockums Chemical AB and Co KG
1980-07-30
Publication of GB1572718A
publication
Critical
patent/GB1572718A/en
Status
Expired
legal-status
Critical
Current
Links
Espacenet
Global Dossier
Discuss
Classifications
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
A61Q15/00—Anti-perspirants or body deodorants
A—HUMAN NECESSITIES
A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
A—HUMAN NECESSITIES
A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
A01N25/12—Powders or granules
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
A61K8/00—Cosmetics or similar toiletry preparations
A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
A61K8/0241—Containing particulates characterized by their shape and/or structure
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
A61K8/00—Cosmetics or similar toiletry preparations
A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
A61K8/25—Silicon; Compounds thereof
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
A61K9/00—Medicinal preparations characterised by special physical form
A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
A61L9/00—Disinfection, sterilisation or deodorisation of air
A61L9/015—Disinfection, sterilisation or deodorisation of air using gaseous or vaporous substances, e.g. ozone
A61L9/04—Disinfection, sterilisation or deodorisation of air using gaseous or vaporous substances, e.g. ozone using substances evaporated in the air without heating
A61L9/046—Disinfection, sterilisation or deodorisation of air using gaseous or vaporous substances, e.g. ozone using substances evaporated in the air without heating with the help of a non-organic compound
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
A61K2800/60—Particulates further characterized by their structure or composition
A61K2800/65—Characterized by the composition of the particulate/core
A61K2800/651—The particulate/core comprising inorganic material
Description
(54) IMPROVEMENTS IN OR RELATING TO METHODS FOR
REDUCING THE DOSES OF BIOLOGICALLY ACTlVE SUBSTANCES
WHILE MAINTAINING THHR BIOLOGICAL EFFECTS
(71) We KOCKUMS CHEMICAL AKTIEBOLAG a Swedish joint-stock company of
Nya Agnesfridsvagen 181 S-213 75 Malmo Sweden do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:
The present invention relates to biologically active compositions and, more particularly, has for its object, by using a new combination of a biologically active substance and a specific carrier, to provide a method for reducing the required dose of biologically active substance while maintaining its biological effect, i.e. to obtain an improved biological effect. l he invention further relates to a biologically active composition for carrying out the method and also the use of such a composition in order to reduce the required amount of biologically active substance when treating a biological system.
The expression «biologically active substance » usually, and in the present context, quite generally is meant to designate compositions containing medicines, killing agents, pesticides, disinfectants (e.g. phenols, chlorinated phenols, such a p-chloro-m-xylenol, tetrabromo o-cresol), biocides, and deodorants.
The use of for instance, pesticides (insecticides, herbicides fungicides, germicides, rodenticides etc.), such as for example DDT (dichlorodiphenyltrichloroethane) has been and still is very extensive, but it has been realized in an ever increasing degree that their use is associated with various risks. Therefore, many countries have regulated the use of pesticides by imposing on them a maximum permissible limit or simply prohibited the use of certain pesticides considered particularly dangerous. However, a prohibition of the use of a pesticide must be weighed against the extant need for the pesticide. In many cases, for instance with regard to DDT, the negative effects of not using the pesticide may seem at least as unfavourable as the risks associated with their use.
To elucidate the problems involved, it may be mentioned that despite pesticide spraying of vegetables, such as tomatoes, the attacks of insects result in damage of a large portion of the tomatoes during distribution. Nevertheless, prohibition of the spraying of tomatoes is being considered with regard to the risks it implies for the consumers. These risks are because the pesticide is present in high concentration on the tomatoes and because of the difficulty of removing the pesticide by washing with water and also because the pesticide penetrates to a certain extent into the tomato itself. Quite naturally, a prohibited spraying of tomatoes would imply considerably reduced production with a reduced supply and higher tomato prices as a result. The same also applies to other fruits and vegetables which are sprayed, such as oranges, apples, pears, lettuce, cauliflower, etc.
Considering that there is already a scarcity of foodstuffs, it is quite unacceptable that foodstuff production, as mentioned above, be further reduced by the prohibition of pesticide spraying. Consequently, it is highly desirable to find a solution to the problem of the two seemingly contradictory requirements that, on the one hand, attacks of insects and diseases should be controlled by spraying and, on the other hand, health and environmental risks owing to the spreading of pesticide poisons should be reduced.
In accordance with that stated above for pesticides, it is known, as regards medicines, that a plurality of these give rise to undesirable side-effects, for instance gastric haemorrhage when use is made of acetylsalicylic acid, owing to the mucous membrane of the stomach being locally exposed to high concentrations of the agent. On account of biochemical processes in the body organs a higher dosage of the medicine concerned is often required than is in reality needed to produce the specific effect aimed at. Part of the medicine is disintegrated or transformed into other compounds, so-called «metabolites», which in many cases produce the undesired side-effects. In special instances, the necessary dosage may be very close to that which gives rise to toxic effect, particularly in sensitive persons.
Thus, it is evident, also in the case of medicines, that in many cases there is a need to provide a method for reducing, if possible, the required dose of the preparation while maintaining the healing effect in order thereby to reduce or eliminate undesired side-effects. A reduced requirement of the amount of expensive, active medicine substance would of course also entail economical advantages.
That stated above as regards pesticides and medicines also applies to the other biologically active substances mentioned by way of introduction, i.e. it would be valuable both from the economical point of view and from that of environment and health if, in some way or other, the use and spreading of the biologically active substance could be reduced.
The present invention has for its object to provide a solution to the problem outlined above, departing from the fundamental idea that by increasing the activity of the biologically active substance in an appropriate fashion. it would be possible to reduce the quantity required for obtaining a desired result and, thus, attain a reduction or elimination of the undesired negative effects.
According to the method of the invention, the reduction of the amount of biologically active substance necessary for obtaining a specific effect. is realized in that a certain amount of the biologically active substance is combined with a particular carrier in certain defined proportions.
Conventional biologically active preparations are available in the form of liquids or powders, the biologically active constituent, when the active preparation is in powder form, being mixed with a carrier. The prior art preparations differ from the present invention in that they use a much higher amount of active substance, in relation to the amount of carrier compared to the present invention. A further critical distinction is that the «carriers» used in the prior art are used as fillers only, that is the active substance is physically admixed with the carrier and not distributed as an even layer on the carrier as in the present invention.
Furthermore the carriers according to the prior art technique mostly have a very low specific surface area of substantially below 50 m2/g, although silica gel having a surface area of more than 50 m2/g has been used. Again, in this case the silica gel has been used as a filler and not as a true carrier.
In contrast to the prior art, at the present invention the biologically active substance or a precursor therefor, possible together with further additives, is evenly distributed as a uniform solvent-free layer on an inactive, solid, finely divided inorganic carrier having a surface area of at least 50 m2/g, the biologically active substance being combined with the carrier in a weight ratio of from 1:106 to 1:1, preferably from 1:104 to 1:102, the dosage of the biologically active substance ranging from 1/2 to 10-5 of the minimum dosage required to produce the same biological effect.
(The values of the surface given in this specification are in accordance with the manufacturer’s specification. Usually, the surface area is determined by adsorption of N2 according to the BET-method.)
The invention also provides a method for reducing the amount of biologically active substance required for obtaining a predetermined biological effect, comprising evenly distributing the biologically active substance or a precursor therefor, together with optional additives, on an inactive, solid, finely divided inorganic carrier having a surface area of at least 50 m2/g in a weight ratio of from 1:106 to 1:1, and selecting the dosage of the biologically active substance to be from 1/2 to 10-‘ of the minimum dosage conventionally required to produce the same effect. The biologically active substance is preferably distributed on the carrier in a weight ratio of from 1:104 to 1:102. In addition, where carriers have previously been used in the prior art, they have been physically mixed with the active substance and used only as fillers, whereas the importance of the present invention lies in providing a carrier evenly layered with the absolute minimum quantity of biologically active substance required to obtain the desired effect. c Useful inorganic carriers may be chosen from inorganic elements and oxides, acids, salts
and polymers thereof. In particular the following types of inorganic carriers should be mentioned: colloidal metal or metalloid oxides, such as alumina and silica; various silicates
and other siliceous compounds, such as asbestos, talc, vermiculite, kieselguhr, diato
maceous earth, mica, expanded mica; and carbonates and phosphates of alkaline earth
metals, such as calcium carbonate, magnesium carbonate and calcium phosphate.
Particularly preferred are the pyrogenic silicas and the alkali metal or alkaline earth metal
silicates as will be explained in greater detail hereinbelow.
In a preferred embodiment of this invention, the carrier has a particle size of about 1 to
about 250 sum.
In conjunction with a biologically active substance intended for oral intake, such as
medicines, too large amounts of inorganic carrier are inappropriate and so, in these cases,
the weight ratio of biologically active substance to carrier is chosen to range from 1:1 to
1:20, the amount of biologically active substance ranging from 1/2 to 1/10 of the amount
normally required when using the biologically active substance alone.
In other, normal cases, e.g. when using pesticides, it is possible to utilize an increased
amount of carrier and a decreased amount of biologically active substance and so, in these
cases, the limits are suitably chosen to range from 1:106 to 1:10 and preferably from 1:104 to
1:102 for the weight ratio of biologically active substance to carrier, and from 10’ to 10-5
for the amount of biologically active substance as compared with the normally required
amount thereof.
Here, the term «inactive» means that the carrier itself does not adversely influence the
effect of the biologically active substance. Thus the carrier should not bind the biologically
active constituent so firmly as to inhibit its effect. A certain interaction of bonding character
may, however, take place between the carrier and the combination of the biologically active
substance with optional additives, as will be described in greated detail hereinbelow.
In a preferred embodiment of the invention the inorganic carrier has a surface area of at
least 200 m2/g.
In a further preferred embodiment of the invention the inorganic carrier comprises silica
or silicate.
In a particularly preferred embodiment of this invention, the silica is a precipitated silica
or a pyrogenic silica prepared by the well-known precipitation or pyrogenic processes.
Precipitated and pyrogenic silicas having surface areas of at least about 200 square meters
per gram are commercially available.
In the presently most preferred embodiment of the invention, the carrier is a pyrogenic
silica which may be obtained in different qualities having a surface area of about 200-1000 m2/g.
According to the invention it is also important that the carrier used be so modified that it
does not itself cause any unbalance in the environment, body or biological system to which
the product is supplied. It is possible to acquire silicon dioxide or silicates of different
particle sizes and surface areas, it being, however, often necessary to modify these
substances with respect to acidity. alkalinity, hydrophilic or hydrophobic character.
Experiments have shown that acidic silicon dioxide can be neutralized by the addition of
ammonia or ammonium hydroxide, other alkalis, calcium hydroxide, magnesium or barium
hydroxides as well as of other metal oxides. Similarly, basic silicon dioxide can be
neutralized by the addition of nitric acid, other mineral acids like phosphoric acids, organic
acids etc. In this way, the carrier material can be carefully modified so as to suit as well as
enrich the particular type of biological system concerned, for instance a certain type of soil.
Consequently, it will be appreciated that, while aiming at reducing the dose of biologically
active substance, the present invention also acts in favour of the natural balance of
environment. Thus, when using pesticides, it is possible to add for instance nitrogen fixing
organisms.
In its purest form, the invention involves a combination only of a biologically active
substance and a carrier, but as will be readily appreciated and as has also been indicated
above. it is of course possible to incorporate various additives, if desirable, without
departing from the scope of the invention. However, such additives constitute only
secondary constituents, the primary constituents being the biologically active substance and
the specific carrier. Various additives may comprise colouring agents and flavourings
(including hormonal attractants) in order to give the preparation attractive colour, smell or
taste, which may be of importance especially for pesticides. The additives further comprise
such agents as have an inhibiting or accelarating effect upon the release of the biologically
active substance. Ionically active substances as well as hydrophobic or hydrophilic
substances are examples of such agents. The additives further incorporate such common,
more or less ‘inert» additives as diluents and solvents for the biologically active substance.
Conventional fillers. such as kaolin, talc. attapulgite, etc., having a surfacenren of less than 200 m2/g may also be incorporated as additives. Hormone type agents may also be used as additives. Since a person killed in the art will easily realise still further examples of suitable additives, an extensive enumeration thereof will be superfluous.
For the sake of simplicity the invention will be described in more detail hereinbelow with reference to pesticides and medicines alone as the biologically active substance and silica as the inorganic carrier. The applicability of the invention to the other categories of biologically active substance and other types of inorganic carriers will be easily realized without it being necessry to burden the present application with particular, detailed description for each separate field of use and each type of carrier.
According to the present invention, it has quite surprisingly been discovered that combining a pesticidally active constituent with a carrier of the kind outlined above and in the above-described manner yields a pesticidal composition of considerably improved effect as compared with corresponding conventional pesticidal compositions. In short, the improved effect of the composition according to the invention can be subdivided as follows: a) The same pesticidal effect as in conventional preparations can be obtained using a considerably smaller amount of pesticidally active constituent, which amount may be as small as 10- to 10-5, or less, of the amount of conventional agent. b) The effect according to a) is further enhanced at a lower pesticidal concentration of the composition, that is, at a reduced ratio of pesticidal constituent to carrier. c) ln some cases, the composition according to the invention may give rise to stimulating effects, for instance that in herbicidal compositions undesired growth is inhibited at the same time as desired growth is stimulated to an unexpected extent. d) The pesticidal composition obtained by the method according to the invention involves minimum health and environmental risks. The reason for this is. on the one hand, that the total amount of pesticide necessary to gain the desired effect is extremely low, in accordance with a) above, and. on the other hand, that the composition can readily be removed by washing from e.g. sprayed vegetables. Besides, owing to the low pesticide content of the pesticidal composition. the risk of the pesticide penetrating into sprayed fruits or vegetables will be almost entirely eliminated.
As to the above-mentioned possibility of readily removing the pesticidal composition of the invention from the treated object, it should be observed here that this property, which is a measure of the strength of the adhesion of the composition to or its bond with the treated material, is important for the total usefulness and effect of the pesticide. Thus, a very strong adhesion to the sprayed object, which may seem advantageous as the pesticide will remain in the contemplated location without being affected by the weather conditions, is unsuitable since it will be difficult or even impossible to remove the pesticide from the object prior to consumption (for instance when the object is a fruit or a vegetable). Moreover. the pesticide may be so firmly bound to the object that its intended effect is reduced, for instance, in that the pesticide is not transferred to the insects attacking a sprayed fruit.
On the other hand, the adhesion of the pesticidal composition to the object should not either be too weak since, in that case. there is a risk that the composition will not adhere at all or, if it adheres. that it will be completely removed from the surfac as a result of the slightest influence, such as rain.
According to the present invention, it has been found that the above inorganic carriers and particularly the silica and silicate carriers imply a very fortunate compromise with regard to the adhesion of the whole pesticidal composition to the sprayed object. It is also possible to modify such compositions according to the invention (by changing the ratio of the active ingredient-containing composition to carrier) so that they may be removed by washing with water at the same time as they adhere sufficiently firmly to the object to maintain the desired biological effect any given length of time. This would prevent the undesired accumulation of active ingredient into the sprayed object (e.g. DDT in tomatoes,
Tables 5 and 6).
In addition to varying the proportion between carrier and active ingredient as described above, other changes can also be effected by choosing carriers which have acidic or basic character.
Preferablv. the carrier is silicon dioxide or an alkali metal or alkaline earth metal silicate including double silicates containing alkali metals or alkaline earth metals, or other metals such as aluminum, boron. zirconium and bismuth (e.g. aluminum silicate, magnesium silicate, magnesium aluminum silicate, calcium silicate) – having a specific surface in excess of 50 m2/g or more. Several of these products are available on the market under different trade names. e.g.
Fluosils Cab-O-Sil (Reg. Trade Mark)
Aerosil (Reg. Trade Mark)
HiSil (Reg. Trade Mark)
ZeosilR
Brite SorbR Quso Manosil (Reg. Trade Mark) Felitet etc.
The pharmaceutical compositions of this invention can also include a solid or liquid pharmaceutically acceptable non-toxic substance. Such pharmaceutical substances can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin. such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water is a preferred suspending medium when the pharmaceutical composition is administered orally or parenterally. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid additives, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, agar, malt, rice, flour, chalk, silica gel, magnesium carbonate, magnesium stearate, sodium stearate, glycerol mono-stearate, talc, sodium chloride, dried skim milk, glycerol, propylene glycol, water ethanol, and the like. These compositions can take the form of suspensions, tablets, pills, capsules, powders, sustained-release formulations and the like. Suitable formulation techniques for the pharmaceutical products of this invention are described in Remington’s
Pharmaceutical Sciences by E. W. Martin, the entire disclosure of which is relied upon and incorporated herein by reference. The compositions will contain an effective therepeutic amount of the biologically active compositions of this invention together with a suitable amount of diluent so as to provide the form for proper administration to the host. It will be understood that the pharmaceutical compositions of this invention can be administered orally, parenterally, or topically to mammals.
The invention and the advantages thereof will be further elucidated hereinbelow with the aid of some Examples. When exemplifying pesticides, the following examples are with neccessity limited to a few illustrative pesticides only. For an exhaustive list of pesticides reference may, however, be made to the article of D. Armstrong Lowe and A.R. Stiles, «Pesticides Nomenclature, specifications, analysis, use, and residues in foods», Progress In
Standardization:l WHO, Geneva, 1974, the whole of which is relied upon and hereby included by reference. Particularly useful pesticides and the most effective ratio of pesticide to carrier may be determined by one skilled in the art by simple experimentation.
The biologically active substance can be deposited in a uniform and even layer on the carrier by dissolving the biologically active substance in a solvent therefor, mixing the carrier with the resulting solution, and evaporating the solvent from the resulting mixture.
The solvent is selected so that it is inert to the biologically active substance; that is, the solvent must not destroy the biological activity of the substance. Also, the solvent must be capable of being evaporated from the mixture at a temperature substantially below the temperature at which the biologically active substance would be denatured or volatilized or sublime. Evaporation of the solvent should be carried out with very gentle agitation of the mixture. which aids in achieving the even and uniform layer on the carrier. The rate of evaporation can be conveniently controlled by regulating the temperature of the mixture, vacuum applied to the apparatus containing the mixture and evaporation time. These factors will of course be dependent upon the volume of solvent to be removed and will be selected so as to avoid the denaturation or volatilization of the biologically active substance.
In the following Examples, methylene chloride was employed as the solvent, and the evaporation time. temperature and vacuum are given. Other solvents can be employed, and optimum conditions determined with a minimum of experimentation.
In the following Examples, use was made of a carrier coated with biologically active substance. In all the cases, the carrier consisted of silica aerogel having a large specific surface area, while the biologically active substance was varied and selected from insecticides. herbicides and medicines. The carrier and the biologically active substance will be described in more detail in the different Examples. The same general method for coating the carrier with the biologically active substance was used in all the Examples, the method being as follows.
A selected amount of carrier according to the invention (300 g) was admixed, under agitation, with methylene chloride (6 liters), or other suitable solvent, for the biologically active substance. Thereafter was added the amount in grams of the biologically active substance which was required in order to bring about the prescribed weight ratio of from 1:106 to 1:1 of biologically active substance to carrier the dosage of the biologically active substance from from 2 to 10-5 of the minimum dosage conventionally required to produce the same effect. Preparations containing the conventional dosage of the biologically active substance were also prepared for comparative purposes. Appropriate additives, such as those earlier indicated, may optionally be added. The resulting mixture was then subjected to the driving off of the solvent by evaporation at a low pressure and temperature (about 20 mm Hg and about 25″C for methylene chloride) for the required period of time (about 20 h) in order completely to eliminate the solvent. The dry product was then gently ground into a powder of a preferred particle size of about 1-250 llm. If such grinding should alter the characteristics of the product, techniques, such as those used in gaschromatography for coating stationary phases on solid supports, can be employed. In principle, the evaporation may be carried out in any appropriate evaporator which permits controlling pressure and temperature in the desired manner. A particularly appropriate apparatus is a rotary flask evaporator of the so-called Rotavapor type. The evaporation should be effected as mildly as possible such that the carrier will be completely coated with biologically active substance, i.e. on its outer surface as well as on the inner parts of the carrier. In case the-evaporation is too vigorous, for instance if the temperature is raised to about 35″C when use is made of methylene chloride as solvent. an uneven concentration of biologically active substance will result on the carrier surface.
Although in the following Examples use has been made of the above described method involving coating from solution and evaporation of the solvent, still other methods may be used according to the invention in order to coat the carrier with biologically active substance. Thus, instead of a solution of the biologically active substance, it is possible to use an emulsion thereof, the biologically active substance beng emulsified in a medium which does not serve as a solvent for the substance. The method involving emulsifying the biologically active substance is particularly applicable when the active substance is sparingly soluble in ordinary solvents.
Another, however not as preferred a method, involves directly coating the carrier with the biologically active substance. In this case, the active substance is sprayed directly onto the carrier under vigorous agitation. for instance by means of ultrasonic sound or a fluidized bed in order to maintain the carrier suspended during the application of the active substance.
Yet another coating method involves vapourizing the biologically active substance and condensing the generated vapor on the carrier, whereby there is obtained an even and uniform coating of the active substance on the carrier.
Irrespective of which method is used for coating the biologically active substance on the carrier. the essential and decisive condition for obtaining a satisfactory final product is that the biologically active substance be coated in an even and uniform layer on the carrier.
Example 1
Using the earlier described process of manufacturing a coated carrier according to the invention three different batches of the carrier (Fluosil, 200 m2/g) were manufactured, coated with the insecticide Malathion (S-[1,2-bis(ethoxycarboxyl)-ethyl]-o,odimethylphosphorus dithioate) in varying coating contents. The first batch was of the composition 1% Malathion/99% carrier, the second batch was of the composition 0.1% Malathion/99.9% carrier, and the third batch was of the composition 0.01% Malathion/ 99.99% carrier. Malathion is normally used in an amount of about ().1 gum’.
Twelve open boxes of PVC-plastic were used for the testing of the preparations produced and the inner sides of the side walls of the boxes were covered with rough abrasive paper.
The surface of each box thus covered with abrasive paper amounted to 0.05 m2. The rough abrasive paper coated surfaces of the boxes were then sprayed with 15 ml of suspension in distilled water of the above preparations in various coating amounts, as will appear from
Table 1. A non-sprayed thirteenth box was used as check box.
Twenty live wood ants were then placed in each of the boxes sprayed with insecticide and in the check box. and the upper sides of the boxes were covered with a fine-mesh net to prevent the ants from escaping. The boxes were then checked once a day for one week with regard to the number of dead ants in each box. The results are given in Table 1.
From Table lit will appear that the pesticide according to the invention is extremely effective also when used in very low contents.
Example 2
To show the superior effect of the pesticide according to the invention, comparative tests were carried out with the insecticide Propoxur (2-isopropoxyphenyl-N-methylcarbamate) as marketed under the trade name BaygonDownload PDF in English
