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US2505681A - Pharmaceutical preparation for relieving itch and killing acaridae - Google Patents

Pharmaceutical preparation for relieving itch and killing acaridae Download PDF

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US2505681A
US2505681A US756550A US75655047A US2505681A US 2505681 A US2505681 A US 2505681A US 756550 A US756550 A US 756550A US 75655047 A US75655047 A US 75655047A US 2505681 A US2505681 A US 2505681A
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acid
parts
ethyl
methyl
crotonic
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Martin Henry
Margot Alfred
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Novartis AG
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JR Geigy AG
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids

Definitions

  • insecticides show no or only insufiicient action against Acaridae.
  • the well-known aza-bis-(p-chlorphenyll- #:pzp-triehlorethane is inactive against most Acaridae.
  • other natural and synthetic insecticides have no marked etlect on Acaridae.
  • Rs means hydrogen or alkyl and Rt means a phenyl radical, which in certain cases contains substituted. non-saltforming WWW,
  • the iollowina compounds have proved to be still edective at a concentration at illm/cmfl against the red spider (Paratetranychus humm-ili) which is particularly dimcult to combat:
  • Croton c acid-o-anisidide 77-79 14 Crotonic acid-N-methyl-pidide 135-140 (0.-1) 15 Crotonic acid-N-ethyl-o-anisido 133-138 (0.15) 16 Crotonic acid-N-boamyl-o-toluididc 134-138 (0.1) 17 3,8- Dimeth lacrylic methyl-an ide 145-146 (13) 18 5,8 Dimeth lacrylic acid-N- eth l-anili e 148-150 (13) 19 0,8- imetbyl-acrylic acid-N- isobutyl-anilide 122-125 (0.3)
  • the compounds have bactericidal properties in addition to being acaricidal. Further since they are practically odouriess and non-toxic in the concentration necessary, they are eminently suitable for the preparation of acaricidal media for use not only to protect plants and stores, but also for general hygiene.
  • the active compounds should not be used in their original form but diluted, thus allowing better and more economical use to be made of them. In general, an approximately 5-10% concentratton in the mixture as used has been found sufficient. However, in certain cases, e. g., with aqueous emulsions, it is possible to employ much lower concentrations with success. In the case 01' preparations in powder form, e. g., media for dusting or powdering where contact with the mites is not so intimate as with liquid preparations, higher concentrations up to e. g. 80% can be utilised. A fine, even dispersion of the active substance in the product when ready for use is of importance as regards the eiiiciency or the medium preparable according to the invention.
  • the active agent In concentrates, e. g., concentrated emulsions, which need to be diluted before use, the active agent must be present in a form which can be dispersed both rapidly and finely.
  • a fine dispersion can be achieved, for example, by mixing and milling the active agent with a solid, pulverulent extending agent to the desired degree of fineness or by impregnating the already milled, finely powdered, solid carrier with a solution of the active agent in a volatile solvent and then removing the latter, which can be recovered when desired, e. g., by suction at reduced pressure.
  • the particle size of the final product should notexceed ca. 300 microns.
  • An advantageous particle size is from 20-80 microns.
  • Such fine dispersions can also be brought about by emulsifying the active ingredient or a solution or the same with. the aid of a dispersing-or emulsifying-agent.
  • the active ingredient is present, dispersed in particles ranging from fine to colloidal size.
  • the particle size should in general not be more than 200 microns.
  • An advantageous particle size is, however, below 10 microns.
  • the invention can also be used in the form of a solution of the active ingredient in suitable inert liquid or semi-solid extending agents where the active agent is dispersed in molecular size.
  • suitable inert liquid or semi-solid extending agents where the active agent is dispersed in molecular size.
  • the mode of employment varies according to the uses intended.
  • solid carriers which are suitable for the manufacture of pulverulent preparations.
  • various inert, porous and pulverulent distributing agents of an inorganic or organic nature may be employed, for example, tricalcium phosphate, 'calcium carbonate in the form of whiting or ground chalk or limestone, kaolin, bole, bentonite, talcum, calcined magnesia, kieselguhr, boric acid, also powdered cork, powdered wood and other pulverulent materials of vegetable origin are suitable carrier substances.
  • wetting and/or dispersing agents such pulverulent preparations can be rendered easily wettable by water so as to
  • Inert solvents suitable for the production of liquid preparations should not be easily inflammable and should be as odourless as possible and, when used properly, should be as non-toxic as possible towards men and animals. Also they should be non-corrosive towards the active component as well as towards the materials of the storage vessels.
  • solvents may be employed forthis purpose: On the one hand, high-boiling oils, for example, oils of vegetable origin, such as castor-oil and the like; on the other hand, also low boiling solvents with a flash point of at least 30 C., such as, for example, carbon tetrachloride, ethylene dichloride, tetrachlorethane, hydrogenated naphthalenes, alkylated naphthalenes, solvent naphtha or the like. Obviously, mixtures of solvents may also be employed. The preparation of solutions is carried out in the usual manner, if required, with the aid of solubility promoters.
  • liquid forms consist of emulsions or suspensions of the active component in water or suitable inert solvents, or of concentrates for preparing such emulsions which can be addilution at the place of use.
  • the active component is mixed with a dispersing or emulsifying agent.
  • the active component may also be dissolved or dispersed in a suitable inert solvent and mixed at the same time or subsequently with a dispersing or emulsifying agent.
  • a suitable concentration and mixing proportion of active component, emulsifying agent and water clear, entirely stable aqueous solutions .(emuisoids) can be obtained.
  • capillarily active substances with an anion-active or a cation-active or a non-ionising component may be employed as dispersing or emulsifying agents.
  • an anion-active or a cation-active or a non-ionising component may be employed as dispersing or emulsifying agents.
  • natural or synthetic soaps Turkey red oil, fatty-alcohol sulphonates, sulphated fats, esters of fatty acids, and the like, also higher molecular quaternary ammonium compounds, as well as condensation products of aliphatic or araliphatic compounds and ethylene oxide, for example, the condensation product of stearin alcohol and ethylene oxide.
  • semi-solid extenders of the nature of a cream, ointment, paste or wax may be employed. into which the active substance can be worked, with the aid of solubility-promoters and/or of emulsifying agents, if required.
  • Such semi-solid preparations are mostly emulsions.
  • Soft soap potassium stearate
  • Vaseline may be mentioned as examples of semi-solid extenders.
  • the active component itself may consist of one or more compounds of the formula defined. Also. it may be used together with other organic synthetic acaricides, insecticides. ovicides, fungicides or bactericidal substances. There may be mentioned, by way of example as other substances of kind; benzyl benzoate, dimethyl thianthrene, phthalonitrile, a: a-blS- chlorophenyl) -fl1fl :fi-trichlorethane or -fi:,B-dichlorethane (DDT and DDD), dinitrocresol, nitrated naphthylarnine, mercury compounds or inorganic substances such as copper compounds, sublimate or sulphur. Composite preparations with a great range of efiectiveness are obtained in this manner.
  • the active component is dissolved or dispersed, with the aid of suitable inert solvents as carrier liquids, if required, in a solvent such as Freon which boils below room temperature at atmospheric pressure.
  • suitable inert solvents as carrier liquids, if required, in a solvent such as Freon which boils below room temperature at atmospheric pressure.
  • compositions Adi'ollowing may be mentioned as further additives which can be mixed with the various forms of composition (Acaridae combating compositions) mentioned: adhesive substances such as casein, salts of fatty acids, glue, resins, fats, albumen-degradation products; wetting agents, solubility promoters, dyestufls and perfumes and, in the case of pulverulent preparations, dust-binding media and so on.
  • adhesive substances such as casein, salts of fatty acids, glue, resins, fats, albumen-degradation products
  • wetting agents solubility promoters, dyestufls and perfumes and, in the case of pulverulent preparations, dust-binding media and so on.
  • the various extenders and additives it is quite possible, by selecting the various extenders and additives, to give the agents such a composition and properties, depending thereon, as to render them suitable for special purposes or conditions of employment.
  • the agents mentioned are mostly liquid preparations.
  • the following are solid preparations: dusting agents, drying powder, strewing agents and such like, and also solid soap preparations which can be employed in the form of moulded pieces.
  • the present Acaridae combating agents can be applied by methods of application usual for insecticides.
  • the Acaridae or the materials for example, plants, roots, root nodules, drugs, textiles, packing materials, cereals, dried fruits, stores of foodstuilfs and fodder, seeds, wood, leather, skins, paper, furs, hair, feathers, articles of all kinds, carpets, Walls and floors, which are to be treated or protected from attack by or harbourage oi Acaridae, can be treated with the active component or with the agents described. by dusting, strewing, sprinkling, painting, smearing, impregnating or other suitable methods.
  • the active compounds having the formula defined have a strong bactericidal or growth-inhibiting action on various sources of infection, such as, e. g.,. Streptococci and Staphylococci.
  • the action on Staphylococcus aureus is revealed in the following experimental results.
  • the tests for bacteriostatic activity were carried out using a modified plate method due to Flemming:
  • the agents prepared according to the invention can also be used as disinfectants in the event of a disinfectant action being necessary or desired. Accordingly, articles of clothing or underwear, implements, utensils and other articles as well as living-rooms, surgical instruments and adjuvants can all be disinfected using the agents.
  • agents which contain the active component herein defined are very suitable for cleaning and washing warm-blooded animals attacked by mites.
  • the following are particularly suitable extending agents for this purpose: liquid extenders, e. g., paraflln oil or vegetable oils such as olive oil, castor oil, sesame oil, camphor oil and also glycerine or solvent-mixtures, e. g., containing glycerine, and so on.
  • Suitable semi-solid extenders e. g., Vaseline, wool fat and the like, or mixtures of such materials.
  • Suitable emulsifying agents for the preparation of aqueous solutions and emulsions are above all soaps, but also sulphonated fats, fatty acid esters and fatty alcohol sulphonates, alkylated aromatic and hydrogenated aromatic sulphonic acids, higher molecular alkoxy carboxylic acids, e. g., alkoxy acetic acids as well as non-ionising emulsifying agents, such as condensation products of fatty alcohols with ethylene oxide.
  • Esters of phosphoric acid are also satisfactory emulsifying agents.
  • emulsions of ointment-like consistency can be produced, for example by employing stearic acid, fatty acid salts and water
  • cellulose ether bases may be employed, or other steeping or swelling substances of animal, vegetable or synthetic origin and water or inorganic substances, such as aluminium-hydroxide gel, in which the active substances can be incorporated,
  • the preparations obtained may be perfumed by the addition of perfumes.
  • good, adhesive pulverulent carrier substances are, talcum, starch, lactose and the like.
  • solids can also be used as carriers, e. g., textile fabrics, cotton, wool, sheets of paper or water-soluble celluloses, which can be for example impregnated with the active ingredient.
  • the bactericidal action can be extended by the addition of phenols, such as pchlor-m-cresol, o-butyl-p-chlorphenol, o-benzylp-chlorphenol, chlorxylenol, cyclohexylphenol, oxydiphenyl and similar compounds.
  • the active ingredients may also be combined with many other disinfectants and fungicides, e. g., with quaternary ammonium compounds such as dodecyl-benzyl-trimethyl ammonium metho-sulphate, oxyquinoline derivatives, colloidal silver preparations, thiocyanic acid etc.
  • an auxiliary substance such as wetting agent can also have bactericidal action and increase thereby the disinfectant action of the medium.
  • Foam producing substances are also particularly effective for this purpose, such as, e. g.. ordinary or synthetic soaps, saponines and so on.
  • the amides used as active ingredients show, in part, a high dissolving power for other compounds which are themselves only difllcultly soluble in the solvents used in the manufacture of acaricidal or disinfectant media.
  • Example 1 5 parts of crotonic-acid-N-ethyl-o-toluidlde (B. P. at 13 mm. 153-155 C.) are ground together with 92 parts of talcum in a ball mill, 2 parts of olein are then added, the whole is again ground and is finally mixed with 1 part of slaked lime. The resulting powder is easily scattered and has good adhesive power. It can be employed for the dusting of rooms and articles or for the protection of plants. A still better distribution of the active substance over or in the carrier material is obtained when the carrier is impregnated with a solution of the active substance, in alcohol or acetone, for example, and the solvent then evaporated.
  • Example 2 15 parts of crotonic-acid-N-ethyl-o-toluldide are mixed with 22.3 parts of kaolin; 4 parts of the sodium salt of dibutylnaphthalenesulphonic acid, 4 parts of casein and 4.7 parts of soda are,
  • crotonic-acid-N-ethyl-otoluidide instead of 15 parts of crotonic-acid-N-ethyl-otoluidide, there may be employed: 5 parts of crotonic-acid-N-ethyl-o-toluidlde and 10 parts of DDT a a-biS- (p-chlorophenyl) 8 p p-trichlorethane) or 10 parts of crotonicv-acid-N-ethyl-otoluidide and 5 parts of said DDT.
  • Example 3 parts of p:,8-dimethylacrylic-acid-N-ethylanilide (melting P t 43 C.) are finely ground together with 20 parts of talc.
  • This concentrate can be'employed .directly as strewing powder for combating mites. However,it may be diluted to any desired concentration, e. g., with bentonite.
  • the addition of .urea gives a strewing-powder particularly effective for purposes of disinfection.
  • Such powders which can also be produced-on other principles are suitable as dusting agents, for example forcombating mites on human or animal skin.
  • Powder preparations for example with a basis of starch-flour, may also be employed for combating mites in storehouses, by mixing with grain for example. If necessary, substances may beadded for improving adhesion, for which purpose, forexample, an addition of 4% of a liquid fatty acid is suitable.
  • Example 4 5 parts of crotonic-acid-N-ethyl-o-toluidide or -m-toluidide are dissolved in 95 parts of alkylated naphthalene (Velsicol) and employed as a household spraying agent.
  • Velsicol alkylated naphthalene
  • Example 5 By mixing 10 parts of crotonic-acid-ll-ethyl-otoluidide with parts of olive oil, a clear solution is obtained which can be employed for combating mites.
  • Example 6 turns into a stable, presumably colloidal solution (emulsoid) when suflicient water is added to make concentration of the active substance about 7%.
  • Turkey-red oil for example, may be employed as i'atty-acid-ester sulphonate.
  • the proportion of active substance to emulsifier may be varied: thus, for example, a similar emulsion is obtained on employ ng 40 parts of crotonic-acid- N-ethyl-o-toluidide and 60 parts of emulsifier.
  • Such solutions or emulsions can be employed with advantage for the most various purposes. Thus. they are suitable for spraying in rooms attacked or threatened by mites. Moreover, articles of different kinds, which have been attacked by mites or which to be protected from attack by mites, may be sprayed with, or impregnated by immersion in. this solution. Sacks made of fabric or paper or other packing materials, which have been impregnated with this solution, are
  • emulsions may be employed for the protection of plants.
  • a solution can be brushed or smeared on.
  • a liquid for treating small animals, it is advantageous to use such a liquid as a bathing liquid.
  • Example 7 30 parts oi crotonic-acid-N-ethyl-o-toluidide, 30 parts of xylene and 40 parts of Turkey-red oil are mixed to give a clear solution which can be emulsified in water in any proportion. This emulslop is employed as in Example 6.
  • Example 8 A homogeneous paste is obtained by stirring iii) parts of crotonic-acid-N-ethyl-o-toluidide with 30 parts of potash soap. By diluting this paste with water, an emulsion is obtained which is suitable as a washing liquid with mite-exterminating and disinfectant properties.
  • Example 9 3y stirring '1 parts of crotonic-acid-N-ethyl-otoluidide with 93 parts of alcoholic soap solution,
  • Example 10 ll parts of p-tolyl-dodecyl-trimethy1-ammonium-methosulphate and 49 parts of crotonicacid-N-ethyl-o-toluidide are dissolved in 49.6 parts of alcohol. emulsion on dilution with water which is suitable for combating mites as described in Example 6. It is also effective, however, for disinfecting equipment of all kinds.
  • Example 11 This clear solution gives an I0 10 mite-exterminating and disinfectant action is obtained, which is specially suitable for treating limits of the skin which have been attacked by Example 12 3 parts of methyl cellulose are soaked in 90 parts of hot water and the swollen mass obtained is intimately mixed with 7 parts of crotonicacid-N-ethyl-o-toluidide. A fat-free acaricidal ointment is thus obtained.
  • methyl cellulose other swelling substances, such as tiiagacanth, gelatins or alginates, may be emp oyed.
  • Example 13 '1 parts of crotonic-acid-N-methyl-anilide (B. P. at 13 mm., 145-448" C.) are stirred with 93 parts of vaselinum flavum until uniform distribution is obtained. An ointment with good acaricidal effect is obtained. By diluting with suitable solvents, the ointment can be given a thinner consistency. An ointment with a good bactericidal action is obtained which is also suitable for combating mites, e. g., Tyroglyphus.
  • Example 14 Elli Examples 15 '3' parts of crotonic-acid-N-ethyl-o-toluidide (B. P. at 13 mm., l53-155 C.) are mixed with 8.5 parts of fatty acid-ester-sulphonate and 84.5 parts oi water. This produces a practically clear, stable, probably colloidal solution suitable for purposes of disinfection, e. g, of surgical til instruments.
  • a concentrate may be prepared, e. g., from parts of crotonlc acid-N-ethyl-o-toluidide and 55 parts of fatty acid-ester-sulphonate. 0n dilution with water there results at first an emulsion which however goes into solution when suflicient water is added to reduce the concentration of the active component to about "1%. 7
  • Example 16 15 parts of fatty alcohol sulphonate, prepared from a fatty alcohol with a. carbon chain of 6-10 carbon atoms, 7 parts of crotonic acid-N-ethylo-toluidide are mixed with 78 parts of water to give an emulsion suitable, for example, for the disinfection oi living-rooms.
  • a pharmaceutical preparation for treating human skin eruption and irritation comprising a creamy preparation containing a substantial amount of a, creamy vehicle carrying an active ingredient distributed therethrough, said active ingredient comprising essentially a carboxylic acid amide of the formula.
  • R1 and R represent a member selected from the group consisting of hydrogen and methyl
  • R3 represents a member selected from the group consisting of hydrogen and alkyl
  • R4 represents a phenyl radical substituted by no more than two members selected from the group consisting of hydrogen, halogen, alkyl and alkoxy radicals, and no more than one of said members being methyl
  • said creamy preparation being adapted to be spread or smeared directly upon the human skin and over affected parts to afford relief for such condition after contact with said aiiected parts, said preparation being non-toxic and nonirritating to such irritated skin and compatible to human skin.
  • a pharmaceutical preparation for direct application to the skin of human beings and effective in relieving skin irritation such as results from mite attacks and the like, comprising a substantial amount of a vehicle, said vehicle being compatible with human skin.
  • said active ingredient comprising essentially a carboxylic acid amide of the formula R1 and R2 represent a member selected from the group consisting of hydrogen and methyl,
  • R3 represents a member selected from the group consisting of hydrogen and alkyl
  • R4 represents a phenyl radical substituted b no more than two members selected from the group consisting of hydrogen, halogen, alkyl and alkoxy radicals, no more than one of said members being methyl.
  • a pharmaceutical preparation for treating human skin eruption and irritation comprising a vehicle, said vehicle being compatible to human skin, containing an active ingredient distributed therethrough.
  • said active ingredient comprising 12 essentially a carboxylic acid amide of the formula CHr-C C-OO-N-Ra wherein R -and R: represent a member selected from the group consisting of hydrogen and methyl, 4 R3 represents a member selected from the group consisting of hydrogen and alkyi, and
  • R4 represents a phenyl radical substituted by no more than two members selected from the group consisting of hydrogen, halogen, alkyl and alkoxy radicals, and no more than one of said members being methyl,
  • said preparation being non-toxic and non-irritating to such skin. and being adapted to be spread or smeared directly upon such skin and over afiected parts to afford relief for such condition after contact with said affected parts, wherein the active ingredient is present in said preparation at a concentration of approximately 5% to approximately 10%.
  • a pharmaceutical preparation for treating human skin eruption and irritation comprising a creamy preparation containing a substantial amount of a creamy vehicle carrying crotonicacid-N-ethyl-anilide, said creamy preparation being adapted to be spread or smeared directly upon the human skin and over affected parts to afford relief for such condition-after contact with said afiected parts, said preparation being nontoxic and non-irritating.
  • a pharmaceutical preparation for treating human skin eruption and irritation comprising a creamy preparation containing a substantial amount of a. creamy vehicle carrying crotonic acid-N-ethyl-p-toluidide, said creamy preparation being adapted to be spread or smeared directly upon the human skin and over affected parts to ailord relief for such condition after contact with said affected parts, said preparation being non-toxic and non-irritating.

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Description

. constant irritation.
Patented Apr. 25, 1950 PHARMACEUTICAL PREPARATION FOR RE- LIEVING ITCH AND KILLING ACARIDAE Henry Martin and Alfred Margot, Basel, Switzerland, sssignors to J. R. Gelgy A. G., Basel, Switzerland, a Swiss firm No Drawing. Application June 23, 1947, Serial No. 756,550. In Switzerland June 28, 1948 7 Claims.
Acaridae (mites) are widespread pests. Many kinds lead a parasitic life on host organisms, such as plants, animals and human beings, causing considerable harm. The condition brought about by mite attacks on humans is called scabies or "the itch. Itch mites are parasitic; burrowing and breeding in the skin, causing eruptions and (See Webster's New International Dictionary under itch mite.") The textbooks on dermatology provide substantially the same information. (Consult Becker and Obermayer, "Modern Dermatology and Syphilology" (1940) p. 486; Schwartz, Tulipan, and Peck. "ccupational Diseases of the Skin (2nd ed. 1947). p. 602; Ormsby and Montgomery, Diseases oi the Skin (6th edition), p. 1138.)
Acaridae difler from insects partly by their blology but also have essential anatomical and physiological dissimilarities. For this reason it is not astonishing that insecticides show no or only insufiicient action against Acaridae. For example, the well-known aza-bis-(p-chlorphenyll- #:pzp-triehlorethane is inactive against most Acaridae. Also other natural and synthetic insecticides have no marked etlect on Acaridae.
It has now been found that amides of no unsaturated carboiiylic acids oi the general formula wherein R1 and R2 mean hydrogen or methyl, 7
Rs means hydrogen or alkyl and Rt means a phenyl radical, which in certain cases contains substituted. non-saltforming WWW,
are very eiiective for combating Acaridae. Am-
The iollowina compounds have proved to be still edective at a concentration at illm/cmfl against the red spider (Paratetranychus humm-ili) which is particularly dimcult to combat:
Action: kill Time Compound Percent Hours Crotonic acid-N-lnethyl-aniiide ##Dimethylam-yllc acid-N-methyl-unilidai. flfi-llgimethylacryhc acid-N-methyl-ptoluie flfi-Dimethylacrylic acld-N-methyl-o-chloranillde h Na- Example B The following test results were observed with flour mites (Aleurobius jarinae) and cheese mites (aurogluphus 8110) at a concentration of 10- g. cm.
Alum. to 2. Compound for. Time i in 'Iimc kills kllls i Orotonicacid-N-methyl- Per cent Hours Per can! Hours anllide 9i 8 160 2 Crotonie scid-N-ethylanllide 24 3 Crotonlcacld-N-methylo-toiu e 83 8 83 8 4 Crotonic aeld-N-ethylo-toiuldldo 91 8 87 8 5 Crotonlcacld-N-methyi- 0.5
p-toluidlde 8 ll Crotonicacld-N-methyl- 7 flfillrlontalrlilllide Hum. 100 2 100 8 me Mr cac 8i 2 a that? at t "15 mo y y cac N-ethyl-anilide 93 M i 100 2 9 flfl-Dimeth lacr licacid- 80 2 w E 'gbniethyg {IO-10 uidirlle. s5 24 91 24 as 0.5 87 2 tiiifi'fififl'fffiff; 100 2 92 a ll BJtDlmethylaci-ylic acid-N-methyl-o' chloranilide 92 2 90 2 i2 Trimethyiacrylic acid- N-methyl-o-toluidide. 75 24 100 Example C The use oi the following compounds in 10% acetone solution resulted in the complete extermination of a further type of mite, Psoroptes cuniculi, inside 48 hours:
Compound ,52 M.Pt.C.
7 Orotonic scid-N-ethyl-p-toluia dide 159-163 (11) 9 157-160 (11) anilide 160-173 (is 10 Crotonic acid-N-ethyl-p-broman e 127-130 (0.1) 11 Crotonic acid-N-ethyl-3,4-dichioranlll e 138-141 (0.1) l2 Crotonic acid-N-etbyl-Z-chlor-fimethFl-anilide 118-121 (0.05) ..i-.-. 13 Croton c acid-o-anisidide 77-79 14 Crotonic acid-N-methyl-pidide 135-140 (0.-1) 15 Crotonic acid-N-ethyl-o-anisido 133-138 (0.15) 16 Crotonic acid-N-boamyl-o-toluididc 134-138 (0.1) 17 3,8- Dimeth lacrylic methyl-an ide 145-146 (13) 18 5,8 Dimeth lacrylic acid-N- eth l-anili e 148-150 (13) 19 0,8- imetbyl-acrylic acid-N- isobutyl-anilide 122-125 (0.3)
20 0,8 Dimethylacrylic acid-N- metbyl-o-toluidide 145-150 (12) 21 8,5 Dimethyl acrylic acid-N- ethyl-o-tolui de 150-152 (13) 22 3,8 Dimethyl acrylic acid-N- isoamyl-o-tol do 126-129 (0.2) 21 3,8 Dimethyl acrylic acid-N- hyl-m-toluidide 155-158 (11) 24 pp Dimethyl acrylic acid-N- ethyi-p-toluidide.-. 160-163 (11) 25 0,3 Dimethyl -scrylic acid-N- methyl-p-toluidide L... 152-155(12) 0,5 Dimethyl acrylic acid-pchloranilide 122-124 27 0,6 Dimethyl acrylic acid-N- cthiyslp-bromamlide 121-126 (0.1) 28 flflimethyl-a iic acid-N- mothyl-o-chioran ide 168-172 (13) 29 5,8 Dimethyl acrylic acid-N- -cthyl-m-ch oranilldc 114-116 (0.05) 30 fl,fl- Dimethyl-acrylic acid-N- ethyl-3,4-dichloranilide..... 121-126 (0. 05) 31 5,8 Dimethyl acrylic acid-N- ethgIQ-chIor-G-methyI-amiide.. 117-118 (0.05) 32 5,8- imethyl-acrylic acid-N- cth l-o-anisidide 120-130 (0.2) 33 fi,flimethyl-acrylic acid-N- methyl-p-anisidide 134-138 (0. 1) 34 6,0 Dimethyl acrylic acid-N- ethyl p-phenetidide.. 143-148 (0.2) 35 Trimethyl-acrylic acid-N-methylanilidide 115-119 (0.4) 36 Trlmethyl-acryllc acid-N-methylo-toluidide....'. 148-150 (12) 37 Trimethyi-acrylic acid-N-ethylo-toluidido 152-156 (12) 38 Trimeth l-acrylic acid-N-ethyl- 3 did 153-157 (12) p-toiuidide 153-157 (12) 40 Trimetbyl-acrylic acid-N-ethylm-chloranilide 121-125 (0.05) 41 Trimethyl-ac lic acld-N-ethylp-bromanili e 121-126 (0. 1) 42 0,8 Dimethyl-acr lic acid-dichlor-aniiide ixture oi 43 T11 il "l'i "'l'd1l""ii1"1 M met y-acry cac -me ypanisidido 130-135 (0.1) 44 Trimethyl-acrylic acid-N-ethylp-phenetidide 139-143 (0. 1)
It should be noted, however, that in most cases the limit of effective concentration is considerably lower. Furthermore, the mites become paralysed in a very short space of time so that already long before death they are unable to cause any more damage. As is explained below, the compounds have bactericidal properties in addition to being acaricidal. Further since they are practically odouriess and non-toxic in the concentration necessary, they are eminently suitable for the preparation of acaricidal media for use not only to protect plants and stores, but also for general hygiene.
The active compounds should not be used in their original form but diluted, thus allowing better and more economical use to be made of them. In general, an approximately 5-10% concentratton in the mixture as used has been found sufficient. However, in certain cases, e. g., with aqueous emulsions, it is possible to employ much lower concentrations with success. In the case 01' preparations in powder form, e. g., media for dusting or powdering where contact with the mites is not so intimate as with liquid preparations, higher concentrations up to e. g. 80% can be utilised. A fine, even dispersion of the active substance in the product when ready for use is of importance as regards the eiiiciency or the medium preparable according to the invention. In concentrates, e. g., concentrated emulsions, which need to be diluted before use, the active agent must be present in a form which can be dispersed both rapidly and finely. Such a fine dispersion can be achieved, for example, by mixing and milling the active agent with a solid, pulverulent extending agent to the desired degree of fineness or by impregnating the already milled, finely powdered, solid carrier with a solution of the active agent in a volatile solvent and then removing the latter, which can be recovered when desired, e. g., by suction at reduced pressure.- The particle size of the final product should notexceed ca. 300 microns. An advantageous particle size is from 20-80 microns.
Such fine dispersions can also be brought about by emulsifying the active ingredient or a solution or the same with. the aid of a dispersing-or emulsifying-agent. In the emulsions the active ingredient is present, dispersed in particles ranging from fine to colloidal size. The particle size should in general not be more than 200 microns. An advantageous particle size is, however, below 10 microns.
The invention can also be used in the form of a solution of the active ingredient in suitable inert liquid or semi-solid extending agents where the active agent is dispersed in molecular size. The mode of employment varies according to the uses intended. As solid carriers, which are suitable for the manufacture of pulverulent preparations. various inert, porous and pulverulent distributing agents of an inorganic or organic nature may be employed, for example, tricalcium phosphate, 'calcium carbonate in the form of whiting or ground chalk or limestone, kaolin, bole, bentonite, talcum, calcined magnesia, kieselguhr, boric acid, also powdered cork, powdered wood and other pulverulent materials of vegetable origin are suitable carrier substances. By adding wetting and/or dispersing agents, such pulverulent preparations can be rendered easily wettable by water so as to obtain stable suspensions suitable for use as spraying agents, for example, in plant protection.
Inert solvents suitable for the production of liquid preparations should not be easily inflammable and should be as odourless as possible and, when used properly, should be as non-toxic as possible towards men and animals. Also they should be non-corrosive towards the active component as well as towards the materials of the storage vessels. The following solvents may be employed forthis purpose: On the one hand, high-boiling oils, for example, oils of vegetable origin, such as castor-oil and the like; on the other hand, also low boiling solvents with a flash point of at least 30 C., such as, for example, carbon tetrachloride, ethylene dichloride, tetrachlorethane, hydrogenated naphthalenes, alkylated naphthalenes, solvent naphtha or the like. Obviously, mixtures of solvents may also be employed. The preparation of solutions is carried out in the usual manner, if required, with the aid of solubility promoters.
Other practical liquid forms consist of emulsions or suspensions of the active component in water or suitable inert solvents, or of concentrates for preparing such emulsions which can be addilution at the place of use. For this purpose, the active component is mixed with a dispersing or emulsifying agent. The active component may also be dissolved or dispersed in a suitable inert solvent and mixed at the same time or subsequently with a dispersing or emulsifying agent. By diluting such a concentrate, for example with water, emulsions or suspensions ready for use are obtained. With a suitable concentration and mixing proportion of active component, emulsifying agent and water, clear, entirely stable aqueous solutions .(emuisoids) can be obtained.
Various capillarily active substances with an anion-active or a cation-active or a non-ionising component may be employed as dispersing or emulsifying agents. There may be mentioned, by way of example, natural or synthetic soaps, Turkey red oil, fatty-alcohol sulphonates, sulphated fats, esters of fatty acids, and the like, also higher molecular quaternary ammonium compounds, as well as condensation products of aliphatic or araliphatic compounds and ethylene oxide, for example, the condensation product of stearin alcohol and ethylene oxide.
For special purposes, semi-solid extenders of the nature of a cream, ointment, paste or wax may be employed. into which the active substance can be worked, with the aid of solubility-promoters and/or of emulsifying agents, if required. Such semi-solid preparations are mostly emulsions. Soft soap (potassium stearate) or Vaseline may be mentioned as examples of semi-solid extenders.
The active component itself may consist of one or more compounds of the formula defined. Also. it may be used together with other organic synthetic acaricides, insecticides. ovicides, fungicides or bactericidal substances. There may be mentioned, by way of example as other substances of kind; benzyl benzoate, dimethyl thianthrene, phthalonitrile, a: a-blS- chlorophenyl) -fl1fl :fi-trichlorethane or -fi:,B-dichlorethane (DDT and DDD), dinitrocresol, nitrated naphthylarnine, mercury compounds or inorganic substances such as copper compounds, sublimate or sulphur. Composite preparations with a great range of efiectiveness are obtained in this manner.
It is also possible to employ the active component in the form of aerosols. For this purpose,
the active component is dissolved or dispersed, with the aid of suitable inert solvents as carrier liquids, if required, in a solvent such as Freon which boils below room temperature at atmospheric pressure. There are thus obtained solutions under pressure which, on being sprayed. give aerosols which are specially suitable for combating mites in closed spaces, in grain silos and other store rooms. The active ingredient, in a suitable solvent, can also be sprayed using compressed gases, e. g., air.
Thei'ollowing may be mentioned as further additives which can be mixed with the various forms of composition (Acaridae combating compositions) mentioned: adhesive substances such as casein, salts of fatty acids, glue, resins, fats, albumen-degradation products; wetting agents, solubility promoters, dyestufls and perfumes and, in the case of pulverulent preparations, dust-binding media and so on. i
It is quite possible, by selecting the various extenders and additives, to give the agents such a composition and properties, depending thereon, as to render them suitable for special purposes or conditions of employment. Thus, it is possible to produce, for example, dips, sprinkling agents, and spraying agents in th form of emulsions or suspensions, as well as emulsions and suspensions for general use and concentrates for their preparation. The agents mentioned are mostly liquid preparations. The following are solid preparations: dusting agents, drying powder, strewing agents and such like, and also solid soap preparations which can be employed in the form of moulded pieces.
The present Acaridae combating agents can be applied by methods of application usual for insecticides. The Acaridae or the materials, for example, plants, roots, root nodules, drugs, textiles, packing materials, cereals, dried fruits, stores of foodstuilfs and fodder, seeds, wood, leather, skins, paper, furs, hair, feathers, articles of all kinds, carpets, Walls and floors, which are to be treated or protected from attack by or harbourage oi Acaridae, can be treated with the active component or with the agents described. by dusting, strewing, sprinkling, painting, smearing, impregnating or other suitable methods.
As mentioned at the beginning, the active compounds having the formula defined have a strong bactericidal or growth-inhibiting action on various sources of infection, such as, e. g.,. Streptococci and Staphylococci. The action on Staphylococcus aureus is revealed in the following experimental results. The tests for bacteriostatic activity were carried out using a modified plate method due to Flemming:
Inhibition Diameter, mm.
Compound (5 mg. quantities) o h staphylo Streptog cocci cocci bum 1 Crotonic acid-N-methyl-otoluidide 144-148/13 7-10 3 o 2 Crotonic acidN-etbyl-o-toluldide. 153-155/13 7-8 10 7 3 Crotonic acid-N-ethyl-p toluidide. 59 7 4i Crotonic acid-N-ethyl-p-bromanliide. 127-130/0. 1 4-5 6 5 Crotonie acid-N-ethyl-2-chlor-fi-rnethyl-anilide. 118-121/0. 05 6-7 7 ti 6 Crotonlc acid-N-methyl-p-anisidide -140/0. l 5 I Crotonic acid-Nethybp-phenetidide 143-147/0. l 7 8 5-5 Dimethvlacrylic acid-N methyl anilide... %46/13 5 9 B B-Dimethylacrylic acid-N methyl-o toluidide 145-150/12 7-11 7 7 10 B d Dlmethyiacrylic acid-N-ethyi-o toiu1dide. -152/13 5 6 6 l1 BzB-Dimethylncrylic acid-N-isopropyl-o-toluidIda-.- 116-119/0. 4 6 l2 fl:fl-Dimethyl acrylic acid-N-methyl p toluidide 152-155/12 6-0 6 9 13 B:B-Dimethylacryllc acid-N-ethyl-p-toluidide -163/11 6-7 4 6 14 fizfl-Dimethyl-acrylic ocid-N-ethyl-Z-chiortmethyl-anilide 117-119/(105 9-14 5 7 15 B:B-Dimethyl-acrylic acid-N-methyl'p-Bnlsidide 134-133/0. 1 B 16 Trimethyl-acryllc acid-N-methyl-o-toluidido. 148-150/12 7 i7 fl:B-'Irimethylacrylic acid-N-ethyl-m-toluldide 153-157/12 i 18 'Irimethyl-acrylic acid-N-ethyln'anlsidide. 168-174/11 6-7 19 Trimethyl-acryiic 8cid-N-methyl-p-anisidida. 130-135/0. l 5 20 'Irimethyl-acrylic acid-N-ethyl-p-phenetidide 139*143/0. 5 m Comparison compound iodo-chloro-oxyquinoline 3-5 Thus the agents prepared according to the invention can also be used as disinfectants in the event of a disinfectant action being necessary or desired. Accordingly, articles of clothing or underwear, implements, utensils and other articles as well as living-rooms, surgical instruments and adjuvants can all be disinfected using the agents.
Also, agents which contain the active component herein defined are very suitable for cleaning and washing warm-blooded animals attacked by mites. The following are particularly suitable extending agents for this purpose: liquid extenders, e. g., paraflln oil or vegetable oils such as olive oil, castor oil, sesame oil, camphor oil and also glycerine or solvent-mixtures, e. g., containing glycerine, and so on. Suitable semi-solid extenders, e. g., Vaseline, wool fat and the like, or mixtures of such materials. Suitable emulsifying agents for the preparation of aqueous solutions and emulsions, for example, are above all soaps, but also sulphonated fats, fatty acid esters and fatty alcohol sulphonates, alkylated aromatic and hydrogenated aromatic sulphonic acids, higher molecular alkoxy carboxylic acids, e. g., alkoxy acetic acids as well as non-ionising emulsifying agents, such as condensation products of fatty alcohols with ethylene oxide. Esters of phosphoric acid are also satisfactory emulsifying agents. However, emulsions of ointment-like consistency can be produced, for example by employing stearic acid, fatty acid salts and water For the production of fat-free ointments, cellulose ether bases may be employed, or other steeping or swelling substances of animal, vegetable or synthetic origin and water or inorganic substances, such as aluminium-hydroxide gel, in which the active substances can be incorporated,
it necessary with the aid of emulsifying agents and/or solubility agents such as parafiln oil. If desired, the preparations obtained may be perfumed by the addition of perfumes. Examples of good, adhesive pulverulent carrier substances are, talcum, starch, lactose and the like.
Many other solids can also be used as carriers, e. g., textile fabrics, cotton, wool, sheets of paper or water-soluble celluloses, which can be for example impregnated with the active ingredient.
Furthermore, the bactericidal action can be extended by the addition of phenols, such as pchlor-m-cresol, o-butyl-p-chlorphenol, o-benzylp-chlorphenol, chlorxylenol, cyclohexylphenol, oxydiphenyl and similar compounds. The active ingredients may also be combined with many other disinfectants and fungicides, e. g., with quaternary ammonium compounds such as dodecyl-benzyl-trimethyl ammonium metho-sulphate, oxyquinoline derivatives, colloidal silver preparations, thiocyanic acid etc. In special cases an auxiliary substance such as wetting agent can also have bactericidal action and increase thereby the disinfectant action of the medium. Foam producing substances are also particularly effective for this purpose, such as, e. g.. ordinary or synthetic soaps, saponines and so on.
The amides used as active ingredients show, in part, a high dissolving power for other compounds which are themselves only difllcultly soluble in the solvents used in the manufacture of acaricidal or disinfectant media. Thus it is possible for example, to dissolve up to10% of 5:7- dichlor-B-oxyquinaldine at room temperature in crotonic acid-N-ethyl-o-toluidide.
Various modes of preparation of the acaricidal mediaaswellastheirusesaredescrlbedinthe 8. following examples. 'e invention is not restricted to these examples, however. The part! are given throughout by weight,
Example 1 5 parts of crotonic-acid-N-ethyl-o-toluidlde (B. P. at 13 mm. 153-155 C.) are ground together with 92 parts of talcum in a ball mill, 2 parts of olein are then added, the whole is again ground and is finally mixed with 1 part of slaked lime. The resulting powder is easily scattered and has good adhesive power. It can be employed for the dusting of rooms and articles or for the protection of plants. A still better distribution of the active substance over or in the carrier material is obtained when the carrier is impregnated with a solution of the active substance, in alcohol or acetone, for example, and the solvent then evaporated.
Example 2 15 parts of crotonic-acid-N-ethyl-o-toluldide are mixed with 22.3 parts of kaolin; 4 parts of the sodium salt of dibutylnaphthalenesulphonic acid, 4 parts of casein and 4.7 parts of soda are,
Instead of 15 parts of crotonic-acid-N-ethyl-otoluidide, there may be employed: 5 parts of crotonic-acid-N-ethyl-o-toluidlde and 10 parts of DDT a a-biS- (p-chlorophenyl) 8 p p-trichlorethane) or 10 parts of crotonicv-acid-N-ethyl-otoluidide and 5 parts of said DDT.
' Example 3 parts of p:,8-dimethylacrylic-acid-N-ethylanilide (melting P t 43 C.) are finely ground together with 20 parts of talc. This concentrate can be'employed .directly as strewing powder for combating mites. However,it may be diluted to any desired concentration, e. g., with bentonite. The addition of .urea gives a strewing-powder particularly effective for purposes of disinfection.
Such powders, which can also be produced-on other principles are suitable as dusting agents, for example forcombating mites on human or animal skin. Powder preparations, for example with a basis of starch-flour, may also be employed for combating mites in storehouses, by mixing with grain for example. If necessary, substances may beadded for improving adhesion, for which purpose, forexample, an addition of 4% of a liquid fatty acid is suitable.
Example 4 5 parts of crotonic-acid-N-ethyl-o-toluidide or -m-toluidide are dissolved in 95 parts of alkylated naphthalene (Velsicol) and employed as a household spraying agent.
Example 5 By mixing 10 parts of crotonic-acid-ll-ethyl-otoluidide with parts of olive oil, a clear solution is obtained which can be employed for combating mites.
Example 6 turns into a stable, presumably colloidal solution (emulsoid) when suflicient water is added to make concentration of the active substance about 7%.
As i'atty-acid-ester sulphonate, Turkey-red oil, for example, may be employed. The proportion of active substance to emulsifier may be varied: thus, for example, a similar emulsion is obtained on employ ng 40 parts of crotonic-acid- N-ethyl-o-toluidide and 60 parts of emulsifier.
Such solutions or emulsions can be employed with advantage for the most various purposes. Thus. they are suitable for spraying in rooms attacked or threatened by mites. Moreover, articles of different kinds, which have been attacked by mites or which to be protected from attack by mites, may be sprayed with, or impregnated by immersion in. this solution. Sacks made of fabric or paper or other packing materials, which have been impregnated with this solution, are
- suitable for the mitefree storage of provisions or other stores. Similarly, these emulsions may be employed for the protection of plants.
Also, parts of the body of human beings and animals which have been attacked by mites can be treated with such a solution. For this purpose, the solution can be brushed or smeared on. For treating small animals, it is advantageous to use such a liquid as a bathing liquid.
Example 7 30 parts oi crotonic-acid-N-ethyl-o-toluidide, 30 parts of xylene and 40 parts of Turkey-red oil are mixed to give a clear solution which can be emulsified in water in any proportion. This emulslop is employed as in Example 6.
Example 8 A homogeneous paste is obtained by stirring iii) parts of crotonic-acid-N-ethyl-o-toluidide with 30 parts of potash soap. By diluting this paste with water, an emulsion is obtained which is suitable as a washing liquid with mite-exterminating and disinfectant properties.
Example 9 3y stirring '1 parts of crotonic-acid-N-ethyl-otoluidide with 93 parts of alcoholic soap solution,
' a clear solution is obtained. More concentrated solutions may also be produced which turn into emulsions on being diluted with water. Instead of 7 parts of crotonic-acid-N-ethyl-o-toluidide, parts of crotonic-acid-N-ethyl-o-toluidide and 2 parts of chloroxylenol may be used, giving a disiniectant washing liquid in dilution with water.
Example 10 ll parts of p-tolyl-dodecyl-trimethy1-ammonium-methosulphate and 49 parts of crotonicacid-N-ethyl-o-toluidide are dissolved in 49.6 parts of alcohol. emulsion on dilution with water which is suitable for combating mites as described in Example 6. It is also effective, however, for disinfecting equipment of all kinds.
Example 11 This clear solution gives an I0 10 mite-exterminating and disinfectant action is obtained, which is specially suitable for treating limits of the skin which have been attacked by Example 12 3 parts of methyl cellulose are soaked in 90 parts of hot water and the swollen mass obtained is intimately mixed with 7 parts of crotonicacid-N-ethyl-o-toluidide. A fat-free acaricidal ointment is thus obtained. Instead of methyl cellulose, other swelling substances, such as tiiagacanth, gelatins or alginates, may be emp oyed.
Example 13 '1 parts of crotonic-acid-N-methyl-anilide (B. P. at 13 mm., 145-448" C.) are stirred with 93 parts of vaselinum flavum until uniform distribution is obtained. An ointment with good acaricidal effect is obtained. By diluting with suitable solvents, the ointment can be given a thinner consistency. An ointment with a good bactericidal action is obtained which is also suitable for combating mites, e. g., Tyroglyphus.
Example 14 Elli Examples 15 '3' parts of crotonic-acid-N-ethyl-o-toluidide (B. P. at 13 mm., l53-155 C.) are mixed with 8.5 parts of fatty acid-ester-sulphonate and 84.5 parts oi water. This produces a practically clear, stable, probably colloidal solution suitable for purposes of disinfection, e. g, of surgical til instruments.
Instead of this working-solution, a concentrate may be prepared, e. g., from parts of crotonlc acid-N-ethyl-o-toluidide and 55 parts of fatty acid-ester-sulphonate. 0n dilution with water there results at first an emulsion which however goes into solution when suflicient water is added to reduce the concentration of the active component to about "1%. 7
till
Example 16 15 parts of fatty alcohol sulphonate, prepared from a fatty alcohol with a. carbon chain of 6-10 carbon atoms, 7 parts of crotonic acid-N-ethylo-toluidide are mixed with 78 parts of water to give an emulsion suitable, for example, for the disinfection oi living-rooms.
Example l? acid-N-ethyl-o-toluidide, said creamypreparation being adapted to be spread or smeared directly upon the human skin and over aflected parts to afford relief for such condition after contact with said affected parts, said preparation being non-toxic and non-irritating.
2.A pharmaceutical preparation for treating human skin eruption and irritation, comprising a creamy preparation containing a substantial amount of a, creamy vehicle carrying an active ingredient distributed therethrough, said active ingredient comprising essentially a carboxylic acid amide of the formula.
R1 and R: represent a member selected from the group consisting of hydrogen and methyl,
R3 represents a member selected from the group consisting of hydrogen and alkyl, and R4 represents a phenyl radical substituted by no more than two members selected from the group consisting of hydrogen, halogen, alkyl and alkoxy radicals, and no more than one of said members being methyl,
said creamy preparation being adapted to be spread or smeared directly upon the human skin and over affected parts to afford relief for such condition after contact with said aiiected parts, said preparation being non-toxic and nonirritating to such irritated skin and compatible to human skin.
3. A pharmaceutical preparation of the character set forth in claim 2 wherein the active ingredient is present in the preparation at a concentration not substantially in excess of 10%.
4. A pharmaceutical preparation for direct application to the skin of human beings and effective in relieving skin irritation such as results from mite attacks and the like, comprising a substantial amount of a vehicle, said vehicle being compatible with human skin. containing an active ingredient distributed therethrough, said active ingredient comprising essentially a carboxylic acid amide of the formula R1 and R2 represent a member selected from the group consisting of hydrogen and methyl,
R3 represents a member selected from the group consisting of hydrogen and alkyl, and
R4 represents a phenyl radical substituted b no more than two members selected from the group consisting of hydrogen, halogen, alkyl and alkoxy radicals, no more than one of said members being methyl.
said preparation being oily, compatible to human skin and being adapted to be spread or smeared directly upon such skin and over affected parts to-afford relief for such condition after contact with said affected parts, wherein the active ingredient is present at a concentration of approximately 5% to approximateiy 5. A pharmaceutical preparation for treating human skin eruption and irritation comprising a vehicle, said vehicle being compatible to human skin, containing an active ingredient distributed therethrough. said active ingredient comprising 12 essentially a carboxylic acid amide of the formula CHr-C C-OO-N-Ra wherein R -and R: represent a member selected from the group consisting of hydrogen and methyl, 4 R3 represents a member selected from the group consisting of hydrogen and alkyi, and
R4 represents a phenyl radical substituted by no more than two members selected from the group consisting of hydrogen, halogen, alkyl and alkoxy radicals, and no more than one of said members being methyl,
said preparation being non-toxic and non-irritating to such skin. and being adapted to be spread or smeared directly upon such skin and over afiected parts to afford relief for such condition after contact with said affected parts, wherein the active ingredient is present in said preparation at a concentration of approximately 5% to approximately 10%.
6. A pharmaceutical preparation for treating human skin eruption and irritation, comprising a creamy preparation containing a substantial amount of a creamy vehicle carrying crotonicacid-N-ethyl-anilide, said creamy preparation being adapted to be spread or smeared directly upon the human skin and over affected parts to afford relief for such condition-after contact with said afiected parts, said preparation being nontoxic and non-irritating.
7. A pharmaceutical preparation for treating human skin eruption and irritation, comprising a creamy preparation containing a substantial amount of a. creamy vehicle carrying crotonic acid-N-ethyl-p-toluidide, said creamy preparation being adapted to be spread or smeared directly upon the human skin and over affected parts to ailord relief for such condition after contact with said affected parts, said preparation being non-toxic and non-irritating.
HENRY MARTIN. ALFRED MARGOT.
REFERENCES CITED The following references are of record in the file of this patent:
UNITED STATES PATENTS Number Name Date.
2,166,120 Bousquet July 18, 1939 2,226,672 Smith Dec. 31, 1940 2,239,832 Smith Apr. 20, 1941 2,350,324 Coleman June 6, 1944 2,354,193 Bowen July 25, 1944 2,368,195. Britten Jan. 30, 1945 OTHER REFERENCES Bischoil: "Ber. Deut. Chem," vol. 34 (1901), pages 2127, 2129, 2130, 2132, 2133 and 2134.
Fichter et al.: J. Prak. Chem, Series 2, vol. 74 (1906), pages 318 and 325.
Lesser: Drug and Cosmetic Industry, June 1943, vol. 52, No. 6, pages 626-627, 690694.
Annand: Bimonthly Progress Report No. 24, Sec. 1, Comm. of Med. Res. of Oil. of Sci. Res. and Devel., June 30, 1945, Subj.: Research on Infections Affecting the Armed Forces. Contract No. OEMcmr-M4331, pages 12-15.
Annand: Ibid, Report No, 25, Aug. 31, 1945, pages 15-47.

Claims (1)

  1. 5. A PHARMACEUTICAL PREPARATION FOR TREATING HUMAN SKIN ERUPTION AND IRRITATION COMPRISING A VEHICLE, SAID VEHICLE BEING COMPATIBLE TO HUMAN SKIN, CONTAINING AN ACTIVE INGREDIENT DISTRIBUTED THERETHROUGH, SAID ACTIVE INGREDIENT COMPRISING ESSENTIALLY A CARBOXYLIC ACID AMIDE OF THE FORMULA
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3151158A (en) * 1964-09-29 New alkenic acid amides and process
US2939164A (en) * 1956-07-06 1960-06-07 Pycope Inc Antiseptic toothbrushes
US3096237A (en) * 1959-05-13 1963-07-02 Bayer Ag Methods of combating mites and fungi
US3075879A (en) * 1960-03-21 1963-01-29 Strully Leonard Vincent Composition of matter and process for the control of drug resistant microorganisms
US3137623A (en) * 1960-08-02 1964-06-16 Geigy Chem Corp Dermatological preparations comprising a corticosteroid and crotonic acid-nu-ethyl-omicron-toluidide

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