US 2149005 A
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Patented Feb. 1939 NITED STATES SHAPED MEDICINAL PREPARATION Max Bockmiihl, Frankfort-on-the-Main-Hochst,
Leonhard Middendorf,Frankfort-on-the-Main- Sindlingen, and Werner Starck, Hofheim in Taunus. Germany,
assignors to Winthrop Chemical Company, Inc., New York, N. Y., a corporation of New York No Drawing. Application November 3, 1936, Serial No. 109,022. In Germany November 9, 1935 4 Claims.
The present invention relates to shaped methermore, the resorption of the vehicle occurs 1.5 very slowly there is the danger that part of the molten mass will flow from the cavities whereby an exact dosing ofthe medicine is made impossible. Finally most of the fats readily become rancid and havethen an irritating efiect 20 upon the mucous membranes. For a long time therefore, the function of basis material for shaped medicinal preparations has been shared by masses prepared from solutions of gelatin, agar-agar and the like in glycerine and water.
25 But also these vehicles show many defects. They dry readily when stored whereby their solubility in the cavities is diminished.
Furthermore, they constitute a nutrient medium for Hyphomycetes and bacteria. They are 30 liable to become mouldy and to form in the cavities an undesired and in certain cases even noxious nutrient medium for pathogenic bacteria.
Attempts which have been made to remove the drawbacks associated with these several vehicles 35 have not shownany practical results. Also swelling bodies which are often used for medicinal preparations to be introduced into the urethra or openings of wounds are not free from drawbacks. They also become hard when they are 40 stored up and then break down in the cavities only with difilculty.
Now we have found that polyalkylene oxides and the derivatives thereof are suitable vehicles for the manufacture of shaped medicinal preparations to be introduced into the cavities. In contradistinction to the fatty vehicles the melting point of the new vehicles is of no importance because their function does not depend on fusion but on dissolution in the secretion of the cavity.
The medicinal preparations which may be prepared according to our present invention have also the following favorable properties. When they are stored they are not decomposed and do not dry. They mix well and can 55 be shaped in a solid as well as in a molten state with most of the medicines. The preparations made with their aid have an unobjectionable solidity and persistence of form. As these new vehicles are soluble in water and in lipoids the medicinal preparation quickly dissolves in the-6 cavities so that the medicines contained in it can rapidly and completely be resorbed.
The new vehicles are physiologically indifferent, nonirritant and odorless and are resistant to the tropical climate. In consequence of the 10 surface activity of the new vehicles a very high degree of distribution of the incorporated medicines is obtained. J
Polyalkylene oxides and especially polyethylene oxide, which has been polymerized up to a waxlike consistency are, for instance, suitable; furthermore the derivatives of the polyalkylene oxides, especially the reaction products of ethylene oxide upon organic compounds which contain hydroxy-, carboxy-, aminoor amido-groups and among these especially those which have been obtained by the action of 10 to 20 molecular proportions of ethylene oxide upon 1 molecular proportion of the organic compound in question especially of a compound containing at least 10 5 carbon atoms. The compounds, for instance, which are obtained by the action of ethylene oxide upon castor oil, ricinole'ic acid or oleyl alcohol are especially suitable.-
For the preparation of the solid medicinal preparations there may, of course, also be used mixtures of the new vehicles. According to the desired purpose there may also be used suitable adjuvants and corrigents, such as glycerine, water, small proportions of fat, hydrocarbons having a high molecular weight and the like.
We have furthermore found that polyalkylene oxides and their derivatives may be used with the same result for the preparation of pills, tablets and the like. It is know that those medicinal preparations, made in known manner, often become hard when they are stored and then break down only very slowly or insufiiciently in the stomach or intestine. The same is true of tablets and dragees. Medicinal preparations to be administered per 0s and free from the disadvantages mentioned may be made by the invention. Also in this case widely differing derivatives of the polyalkyiene oxides may be used. Adjuvants of quite difierent kinds may also be used therewith.
The following examples illustrate the invention but they are not intended to limit it thereto; the
parts are by weight:
(1) Morphine suppositories (4) Papaverine tablets Parts Parts Morphine hydrochloride 0.5 Papaverine hydrochloride 4 Very pure, bleached polyethylene oxide 227 Very pure, bleached polyethylene oxide 33 Condensation product from ethylene oxide Glycerine 3 and ricinoleic acid 22. 3 Water 22. 2
(2) Suppositories prepared from dimethylaminophenyldimethylpyrazolone, sodium phenyldimethvlpurazolonemethylammomethane sulfanate and urethane Parts Dimethylaminophenyldimethylpyrazolone 40 Sodium phenyldimethylpyrazolonemethylaminomethane sulfonate 60 Urethane 45 Very pure, bleached polyethylene oxide 250 (3),Small rods containing the compound prepared from gelatose with silver nitrate Parts The compound prepared from gelatose with silver nitra 0. 25 Very pure, bleached polyethylene oxide-" 42 The condensation product from ethylene oxide and ricinoleic acid 4 45 Water 4 The mass which is prepared as described in Example l is poured into hollow moulds for rods.
The papaverine is made into a paste with the glycerine and the polyethylene oxide which has been liquefied by heating it on a steam bath is then stirred in. The mass is either poured into hollow moulds and allowed to cool or it is poured onto a glass plate or the like where it is allowed to harden and is then cut to form tablets.
(5) Pills prepared from cafl'eine-phenylethylmalonyl-urea Parts Cafl ln 2.5 Phenylethylmalonyl-urea 5 Very pure, bleached polyethylene oxide 15 Sugar syrup 5 The phenylethylmalonyl-urea and the cafieine are mixed with the polyethylene oxide which previously has been pulverized and the mixture is kneaded with the sugar syrup to a plastic mass. Pills are formed from this mass in the usual manner.
We claim: I
1. Shaped medicinal preparations comprising a pharmacologically active substance and a vehicle consisting of polyethylene oxide.
2. Shaped medicinal preparations comprising a pharmacologically active substance, a compound obtained by the interaction of ethylene oxide and ricinoleic acid and a vehicle consisting of polyethylene oxide.
3. Shaped medicinal preparations comprising a pharmacologically active substance, a compound obtained by the interaction of ethylene oxide and castor oil and a vehicle consisting of polyethylene oxide. a
4. Shaped medicinal preparations comprising a pharmacologically active substance, 8. compound obtained by the interaction of ethylene oxide and oleyl alcohol and a vehicle consisting of polyethylene oxide.
MAX BocKMiiHL. LEONHARD MIDDENDORF. WERNER STARCK.