|Publication number||US3325472 A|
|Publication date||Jun 13, 1967|
|Filing date||Jun 18, 1964|
|Priority date||Jun 18, 1964|
|Also published as||DE1645283A1, DE1645283B2, DE1645283C3|
|Publication number||US 3325472 A, US 3325472A, US-A-3325472, US3325472 A, US3325472A|
|Inventors||Raymond R Sackler|
|Original Assignee||Mortimer D Sackler, Raymond R Sackler|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (8), Referenced by (16), Classifications (30)|
|External Links: USPTO, USPTO Assignment, Espacenet|
United States Patent 3,325,472 POLYCYCLOHEXQS -POLYOXYETHYLENE- GLYCOL SUPPOSITORY BASES Raymond R. Sackler, Roslyn, N.Y., assignor to Mortimer D. Sackler and Raymond R. Sacltler, Yonkers,
N.Y., a copartnership No Drawing. Filed June 18, 1964, Ser. No. 376,260 16 Claims. (Cl. 260-409) This invention relates to new and novel pharmaceutical compositions which are suitable for use as a suppository base and which may be formed into suppositories for rectal insertion, as well as used as a carrier for pharmacologically active substances to be administered by suppository route. In particular, this invention relates to hydrogen-bonded compounds comprising polymeric poloxyethylene glycol, having a molecular weight of from 200 to 6000, which are hydrogen-bonded to polymeric vegetable polycyclohexose compounds, as for example, gum guar, algin, pectin and carboxymethylcellulose. This hydrogen-bonded compound provides an advantageous carrier for pharmacologically active substances, or it may be formed into suppositories which may be used directly for insertion into the rectum.
This application is a continuation-impart of my copending United States patent application, Ser. No. 296,477, which was filed July 22,1963 now abandoned.
Suppositories are conical or elliptical medicated solids intended for insertion into one of the several orifices of the body, excluding the mouth. Insertion into the body should be simple and easy, without incidental tissue trauma or pain. After insertion, the suppository should disintegrate readily, that is, either melt, dissolve or disperse, thereby distributing the active therapeutic substances and/or the suppository base within the body cavity. Suppositories should be of a shape to permit the easy insertion into the particular body cavity for which they are intended and be of suflicient weight to provide an indicated therapeutic dose of the drug, when serving as a pharmaceutical carrier.
A suppository may be utilized to obtain either a local or systemic effect. The action of a drug administered by suppository, but which is not absorbed through the mucous membrane lining the orifice of insertion, is considered to be a local effect in contrast to the effect resulting after the use of a suppository from which the active ingredients are absorbed into the systemic circulation. Emollients, astringents, antibiotics and certain anti-inflammatory agents are examples of classes of compound which may be utilized in combination with a suppository base to achieve a local effect, whereas a Wide variety of drugs, such as hormones, analgesics, sedatives, alkaloids, certain soluble inorganic and organic synthetic therapeutic compounds, have been successfully administered by the suppository route fortheir systemic effect. When a drug is absorbed across the mucous membrane surface, the suppository route of administration will usually result in a systemic effect, just as if the drug had been given orally. The principal differences which distinguish the suppository route of administration in these instances, from the oral route of administration, are the inset, duration and intensity of action, all of which are dependent upon the dosage and rate of release and absorption of the active drug from the suppository carrier. The rich blood supply of the tissues of the rectum and vagina provide a suitable means for obtaining a systemic blood level of a drug, thereby avoiding the upper gastrointestinal tract which is not desirable in those instances where individual patient intolerance to a drug, or destruction of the drug by the digestive juices, prevents its oral administration.
Thus, it has been shown that the sytemic onset of action of drugs administered my the suppository route may be more prompt than when the same drug is administered orally. The difference in time is usually ascribed to the longer period that such drugs remain in the stomach after oral administration. Thus, for example, in the case of most alkaloids, the pharmacologic response is observed within 3 to 5 minutes after introduction into the rectum by suppository medication, an effect which is much more rapid than that observed after the oral use if the same substance.
Suppositores may be prepared from either water-immiscible fatty substances or water-miscible hydrophilic substances. Among the fatty substances which have been suggested as bases for suppositories are lard, theobroma oil, resins and fats. Among this group of suppository compounds are included such substances as white wax, spermacetic, oleic acid and stearic acid mixtures, and hydrogenated vegetable oils. The aqueous immiscibility of the fatty suppository substance is a general limitation of this class of compounds being used as carriers for certain pharmacologically active polar compounds. The hydrophobic character of the lipid material causes pooling in the essentially aqueous character of the rectum, and thereby inhibits the release and transfer of the active material. This nonuniform distribution of medicament results in both poor absorption and an uneven rate of absorption. Some fatty components, such as white wax and spermaceti, do not melt at body temperature and require other additives to provide a composition which will permit disintegration of the suppository mass at body temperature. The vegetable oils and waxes have still another disadvantage in that rancidity will occur unless suitable preservatives are added, while the use of oleic and stearic acid mixtures is limited for those medicaments which do not react with these acid components. Furthermore, the mixture of organic acids may cause a local issue irritant elfect in some individuals.
In order to avoid the basic limitations of the fatty suppository bases, attention was directed toward hydrophilic aqueous miscible substances, such as the polyoxyethylene glycols, glycerinated gelatin and polymerized ethylene oxide derivatives of glycols. However, as a group, these compounds possess disadvantages which detract from their use and are unsuitable for use with a number of drugs because of pharmaceutical incompatability. This is especially important when considering drugs which undergo hydrolytic decomposition in the presence of water and the glycols. The aqueous miscible suppository bases are prepared to contain a certain amount of water and also since these bases are hygroscopic, special packaging techniques must be used to maintain their stability under storage conditions. Problems of uniform dispersibility and disintegration have been encountered with these suppository bases. Since, in general, suppositories prepared with these materials will not melt at body temperature, varying amounts of Water are required for their dispersion and because of the limited fluid sometimes available in the rectum, variable results occur.
Suppositories are manufactured by two basic processes-the hot pour technique and the compressionextrusion technique. The hot pour technique involves the pouring of the molten suppository composition into a suitable mold, which is then cooled below the melting point of the suppository base. Upon hardening, it assumes the desired form and shape. The compression-extrusion technique involves the packing of the mold with the suppository base under pressure. This method has the advantage that the base is solid at all times and therefore the dispersed materials do not sediment as they would when liquid compositions are utilized during the hot pour m9 technique. The high speed production of suppositir-ies required by commerce makes the extrusion technique a preferred method. However, this procedure has an inherent limitation in that the elevated pressures required by the high speed production causes an elevated temperature of the suppository base with consequent partial liquifaction. While suitable additives have been devised to maintain both a uniform consistency of the suppository mass as well as a lubricant effect so that the finished suppositories may be readily ejected from the mold, these additives result in a harder suppository which may cause tissue trauma when inserted. The hard suppository is more apt to cause tissue trauma to the sensitive ano-rectal tissues of the infant as well as in those patients presenting ano-rectal disease, such as hemorrhoids, ano-rectal fistula and fissure, or during the immediate post-operative period following proctologic surgery.
Through the use of the products of the present invention, the inherent limitations for both the fatty and the water-miscible bases are avoided. When a polycyclohexose compound, as for example, guar gum, algin, carboxymethylcellulose, and pectin, are mixed with polyoxyethylene glycol having a molecular weight of from 200 to 6000, which are known in commerce as Carbowaxes, a hydrogen bonded chelation compound is formed. The new suppository compound is a homogeneous substance, having no reproducible physical and chemical properties and which is capable of being shaped and formed into suppositories which have new desirable and advantageous properties. The new suppository compound is compatible with pharmacologically active substances and disintegrates, both rapidly and uniformly, after insertion into the body.
Conductance measurements with A Type-RC Conductivity Bridge of dispersions of gum guar and polyoxyethylene glycol, establish the presence of the hydrogenbonded chelation compound formation. The formation of the new hydrogen-bonded chelation compound is demonstrated through the measurement of the conductance of the product of the reaction of gum guar and polyoxyethylene glycol with the unexpected finding that this value is less than the sum of the conductance of the individual moieties. The conductance for a mixture of gum guar and polyoxyethylene glycol in which there is no hydrogen-bonded chelation complex compound formation would be expected to be the sum of the individual conductance measurements for the separate components of the mixture. Thus, we find that the resistance determined for gum guar at 1 percent concentration and at pH 5.55, is 1225 ohms and the conductance value is 808 mhos X 10 The conductance determined for polyoxyethylene glycol, having an average molecular weight of 400, and which is known in the trade as Carbowax 400, at 1 percent concentration and pH 6.15, has a resistance of 17,300 ohms and a conductance of 57.5 mhos The hydrogen-bonded chelation compound formed by guam guar and polyoxyethylene glycol-400 at the same concentration, has a pH of 5.95, has an average resistance of 1420: 130 ohms and an average conductance of 705 mhos 10 The values determined are reproducitale and characteristic for the particuluar hydrogen-bonded chelation compound formed. When larger molecular weight polyoxyethylene glycol compounds are used as reagents, such as polyoxyethylene glycol 4,000, the degree of hydrogen-bonded formation is lessened, so that, for example, the conductance for the chelation compound of gum guar-polyoxyethylene glycol 4,000 has a conductance of 795 mhos 10 If hydrogen-bond chelation compound formation has not occurred, then the conductance for the mixture would be 865.5 n1h0s 10 When a suppository prepared with this new compound is inserted into the body, the hydrophilic character of the base causes it to absorb moisture, producing a uniform disintegration and dispersion of the suppository. The resultant increases surface area of the dispersed hydrophilic materials coats the hydrophilic ano-rectal mucosa to provide intimate contact with the tissue barrier, thereby facilitating absorption for those substances that tended to enter the systemic circulation or, to permit the full therapeutic activity for those agents intended to exert a local effect. Thus, there is no pooling of the suppository ingredients as would occur when hydrophobic suppository materials are used, nor is there a dependence upon large amounts of water to cause disintegration when hydrophilic compositions are used. This unique effect is achieved because of the desirable coefficient of expansion of the hydrogen-bonded chelation compound which results in a surface shearing action which produces a rapid disintegration of the suppository. This effect is independent of the melting point of the compound and is initiated with only minimal amounts of moisture. The unique physical characteristics of the hydrogen-bonded chelation suppository compound permits high pressure rapid molding without surface liquifaction and does not require additive stabilizers or lubricants to facilitate the ejection of the formed suppository from the mold. When the hot pour technique is used, the high viscosity of the suppository mass retards sedimentation so that a uniform dispersion is maintained even in the liquid state. The new suppository compound does not turn rancid and is stable under the ordinary conditions of storage.
The new suppository base is non-irritating to the anorectal mucosa and may be introduced even in the immediate post-operative period.
In order to form the new suppository chelation compound, the selected polycyclohexose compound is mixed with the polyoxyethylene glycol and the mixtured warmed to a temperature of between 50 C. and C., for a period of at least 15 minutes. While the lower temperature range of 40 C. may be used for the lower molecular weight polyoxyethylene glycols, as for example, those polyoxyethylene glycols having a molecular weight of from 200 to 600, the upper temperature range of 65 C. is utilized for those members of the polyoxyethylene glycols series having a molecuular weight of from 1000 to 6000. During the warming phase, the mixture is stirred so that a uniform distribution of the polycyclohexose compound in the polyoxyethylene glycol is achieved. After the desired warming period is ended, the stirring is continued while the compound is allowed to cool. After cooling to room temperature, a plastic, solid, chelation compound results which may be readily shaped into the desired suppository and which is readily dispersible in aqueous fluids.
The ratio of polycyclohexose compound to polyoxyethylene compound required to form the desired hydrogenbonded chelation compound ranges from 5 parts by weight of the polycyclohexose and 95 parts by weight of the polyoxyethylene glycol, to 40 parts by weight of the polycyclohexose to 60 parts by weight of the polyoxyethylene glycol. A preferred range of ratio concentration of the components is between 10 parts to 25 parts by weight of the polycyclohexose to 90 parts to parts by weight of the polyoxyethylene glycol. The exact ratio of components selected to form the new hydrogen-bonded chelation compound suppository base depends upon the particular intended use of the suppository and its manufacturing technique to be employed. Thus, a suppository intended to be manufactured by high speed compression apparatus, will require a higher degree of hydrogenbonding to withstand the increased pressures and stresses and consequently the upper limits of range of the ratio of concentration of components will be used. Similarly, when the hot pour technique is to be utilized for a suppository containing appreciable quantities of suspended active ingredients, the upper concentrations will be preferred because of the increased viscosity of the molten new suppository compound. When a preparation is intended as a carrier for medication to be utilized in pediatric practice, the lower ranges of the ratio of concentration of components are more desirable to derive a more pliable suppository mass.
When it is desired to utilize this new suppository base material for the manufacture of pharmaceutically acceptable suppositories, the appropriate quantity of prepared new suppository compound is placed in a suitable container and melted over a water bath. Should it be preferred to utilize the dry composition, then the solid suppository compound is subdivided into coarse granular particles, either by passing through a comminuting apparatus or by trituration. The pharmacologically active material is then added to the suppository base whether molten or shredded and is uniformly dispersed. The suppositories are then manufactured either by compressionextrusion or through molding by the hot pour technique.
Examples of drugs which may be incorporated with the suppository base and then shaped into suppositories of suitable size for therapeutic administration are, antibiotics, as for example, tetracycline, penicillin, chlortetracycline, neomycin, bacitracin, polymyxin and the sulfa drugs; antiseptic agents; germicides; contraceptive agents; hormones, such as testosterone, estrone, hexesterol, stilbestrol, thyroid hormone, thyroid substance, thyroxin; the steroids, such as hydrocortisone, cortisone-alcohol, prednisolone; analeptic agents, such as caffeine, theophyllin and metrazole; diuretic compounds such as chlorthiazine, hydrochlorthiazine, fiuoromethiazine; sedative agents, such as barbituric acid derivatives, hydantoin derivatives, central nervous system stimulants, such as amphetamine; analgesic medication such as aspirin, choline salicyate, calcium salicylate, N-methylglucammonium salicylate, betaine salicylate, acetopheneditin, phenyl butazone, and laxative medications such as phenolphthalein, emadin, isatin, senna, cascara and extracts of these; cardiotonic agents, such as digitalis, oubain and quinidine salts and the narcotic medications, including the opium derivatives. The concentration of these therapeutic agents to be used in the suppository base is the full therapeutic dosage which is used in therapy, since there is no interference with the pharmacologic action by the new suppository base compound.
The following examples illustrate the scope of this invention.
Example 1 In a suitable container is placed 400 gms. of polyoxyethylene glycol-400 and 600 grams of polyoxyethylene glycol-1000. The mixture is warmed to about 50 C., until complete soiution is achieved and then 1 kilogram of polyoxyethylene glycol-6000 is added in small increments to the warm solution. When all of the polyoxyethylene glycol-6000 has been added, the mixture is stirred while 200 gms. of gum guar is added in small increments with stirring. After all of the gum guar has been added, the stirring is continued while the reaction mixture is warmed at a temperature of between 55 and 65 C. for one-half hour, after which time it is allowed to cool to room temperature. Upon cooling a cream colored waxy solid is obtained which has a melting point of 57-59 C. A 2 gm. sample is completely dispersed in ml. of water Within 20 minutes, at 37 C. Although the melting point of the compound is between 57 and 59 C., it may be molded at a temperature of C. During the molding operation for the preparation of suppositories, the new base assumes a rigid form within one minute. When high speed compression molding procedures are used to form suppositories, the new compound may be worked with at temperature range of from room temperature to as high as C. It will be found that the suppositories are ejected rapidly and smoothly, and without sticking to the die.
The hardness of the suppository is determined by the extent of hydrogen-bond formation between the polycyclohexose compound and the polyoxyethylene glycol. Thus, the range in concentration for the different molecular weight polyoxyethylene glycol compounds may vary with the desired texture of the suppository, while the hardness will depend directly upon the degree of hydrogen-bonded chelation linkage present.
Example 2 In a suitable container is placed l600 gms. of polyoxyethylene glycol-400 and to this is added 600 gms. of gum guar. The mixture is warmed to about 50 C. and stirred for a period of one-half hour, after which time it is allowed to cool to room temperature. Upon cooling the compound becomes a creamy, waxy, solid having a melting point of 5 0 C. to 53 C. It has a complete dispersion in water at 37 C. within 20 minutes. The conductance of a 1 percent concentration at pH 5.95, is 705215 mhos X 10 This conductance value establishes that hydrogen-bonding occurs since the conductance for the new compound is less than the sum of the conductance values for the separate, individual components. Gum guar has a conductance of 808 mhos 10 and polyoxyethylene glycol-400 has a conductance of 46.5 mhos 10 Example 3 In a suitable container is placed 700 gms. of polyoxyethylene glycol-4000 and 300 gms. of gum guar. The mixture is warmed to a temperature of 60 C. which is maintained over a period of 1 hour, with constant stirring. At the end of this time, the heating is stopped and the molten material is allowed to cool to room temperature. While cooling a hard, solid mass results which has a melting point of from 6l-63 C. A 2 gram sample shows complete dispersion in 20 ml. of water, at 37 C. within 20 minutes. The pH of a 1 percent dispersion is 6.02 and it shows a conductance of 795 mhos 10 Example 4 In place of the gum guar described in Examples 1 through 3 above, there may be substituted in equal quantities, algin, pectin and carboxymethylcellulose. The remainder of the steps being the same.
Example 5 In place of the polyoxyethylene glycol400, polyoxyethylene glycol-1000, and polyoxyethylene glycol-6000 described in Examples 1 through 4 above, there may be substituted wholly, or in part, a polyoxyethylene glycol having a molecular weight range within 200 and 6000. The particular polyoxyethylene glycol to be used depends upon the desired texture in the finishedsuppository. When larger amounts of a lower molecular weight polyoxyethylene glycol are used, then the texture of the finished suppository will be more wax-like. Such a suppository will be less friable and may be prepared in long, narrow, rodlike shapes. The exact amount of each of the particular polyoxyethylene glycol to be used will depend upon the particular purpose and method of manufacture for the suppository.
The formation of the hydrogen-bonded chelation compound occurs more readily with the lower molecular weight polyoxyethylene glycol compounds than with the higher molecular weight compounds. However, in all instances, hydrogen-bonded chelation compound formation may be shown through the measurement of the conductance value for the new compound formed. The hydrogen bonding bet-ween the gum guar and the polyoxyethylene glycol is clearly established by the unexpected finding of a conductance which is less than the sum of the separate conductance of the individual components. The remainder of the steps being the same.
Example 6 To gms. of a compound prepared according to the method described in Examples 1 through 5 above, and which has been melted on a water-bath, at a temperature below 65 C., is added 15 gms. of powdered aspirin, U.S.P. The aspirin should be subdivided to at least standard mesh particle size, prior to adding to the molten base. The mixture is stirred to achieve uniform distribution of the aspirin and then removed from the water-bath to cool to room temperature. When the whole has solidified, the mixture is chilled and passed through a number 8 standard mesh screen. The powdered suppository material is then filled into a compression-extrusion apparatus fitted with a suitable mold, so that suppositories weighing 2 gm. each may be prepared. Should it be desired to use a hot pour molding technique, for the preparation of suppositories, then the molten mass is poured directly into the mold and allowed to cool therein. A mold of sufficient size and shape to prepare a 2 gm. suppository is utilized. The suppositories are administered from 1 to six times daily, depending upon the needs of the patient.
Example 7 In place of aspirin used in Example 6 above, there may be substituted any of the following therapeutic compounds, or mixtures of these, as well as other compatible active therapeutic compounds, so that the concentration of the therapeutic agent, per suppository, will be within the active therapeutic range, as for example the range described for each of the compounds noted below.
Range of concentration per Active agent: suppository, mg:
Erythromycin 10O to 250 Penicillin 200 to 500 tetracycline l to 250 Oxytetracycline l0O to 250 Chlortetracycline 100 to 250 Piperazine citrate "100 to 250 Pyrillamine malleate 25 to 50 Promethazine hydrochloride to 50 Pheniramine malleate 5 to 25 Sulfanilamide lO0 to 500 Sulftathiazole l00 to 500 Sulfamerzine 100 to 500 Sulfacetamide l00 to 500 Phthallyl sulfathiazole l00 to 500 Amphetamine sulfate 5 to Cyclopentamine hydrochloride l5 to Isoxsuprine hydrochloride 5 to 10 Butabarbital l5 to 60 Phenobarbital l5 to 60 Secobarbital l5 to 60 Pentobarbital l5 to 60 Chlorpromazine 25 to 100 Fluphenazine O.25 to 5 Mepazine 25 to 100 Promazine l0 to 200 Desoxycorticosterone acetate 25 to 50 Cortisone acetate 5 to 25 Dexamethasone 0.5 to l Hydrocortisone cyclopentil propionate l to 5 Prednisolone acetate 5 to 25 Estradiol 0.1 to 1.0 Dieenestrol 0.1 to 10 Diethylstilbestrol 0.5 to 10 Hexestrol 05 to 5 Methyltestosterone 5 to 25 Sodium levothyroxin 0.1 to 5 Digitoxin ..0.1 to 0.2 GitOXin O.l to 6.2 Digitalis powder "100 to 200 Quinidine sulfate 200 to 400 Quinidine polygalacturonate 200 to 300 Quinidine gluconate 200 to 300 Quinidine galacturonate 200 to 300 N-methylglucammonium salicylate 50 to 300 Choline salicylate 50 to 300 Phenacetin 50 to 300 Caffeine 5 to Ephedrine 5 to 30 Range of concentration per Active agent: suppository, mg:
Theophyllin 5 to 30 Senna 5 to 300 Cascara 25 to 100 Isatin 5 to 15 Sodium liothyronine 5 mcg to 50 mcg.
Suppositories prepared with these and other therapeutic agents, which are pharmaceutically suitable for suppository administration, are stable and will result in the full desired therapeutic effect for the respective active ingredients. Such suppositories are administered from 1 to 6 times daily, depending upon the need of the patient, the pharmacologic effects of the active ingredient and the status of the disease present.
Suppositories prepared according to the procedures described above are a desirable means of administering pharmacologically active materials. It will be found that these are completely dispersible in minimal quanties of aqueous fluid, usually within a period of 20 minutes, at
body temperature, notwithstanding that the melting point of the base is higher than body temperature. The dispersion of the suppository is achieved through a unique action. When the suppository is introduced into the body cavity the hydrophilic properties of the base adsorbs moisture, causing a unilateral swelling action. The expansion of the hyodrogen-bonded polycyclohexose moiety facilitates the uniform dispersion of the suppository base and the active ingredient. The hydrophilic character of the suppository base tends to aid adherence of the dispersed substances as a surface film on the mucosal wall of the body cavity. This intimate contact promotes the rapid transfer and absorption of pharmacologically active material. In the instances where the pharmacologically active material does not traverse the mucosal tissue, then the intimate tissue contact provided by such uniform dispersion of the suppository base and active ingredient, results in a superior local therapeutic effect.
Example 8 Suppositories prepared from a compound obtained as a result of Examples 1 through 5 above, may be used to induce laxation or to provide an emollient coating to the ano-rectal mucosa. When it is desired to utilize the suppository materials in such manner, then the suppository mass is shaped into suppositories, having an average weight of from 0.50 gms. to 2.0 gms. each. The suppositories may be manufactured by either the cold compression-extrusion technique or the hot pour method. Such suppositories may be inserted into the rectum from 1 to 4 times daily, depending upon the particular patient need. in instances, where a lubricant effect is desired to induce laxation, the use may be at morning and night. When a protective elfect to the ano-rectal mucosa is dedesired, then a more frequent usage is indicated and the suppository may be inserted up to 4 times daily.
What is claimed is:
1. A compound comprising a polymeric polycyclohexose compound selected from the group consisting of gum guar, pectin, algin, canboxymethylcellulose and mixtures of these and a polyoxyethylene glycol selected from the group consisting of polyoxyethylene glycols with a molecular weight of from 200 to 6000.
2. A compound comprising from 5 to parts by weight of a polymeric polycyclohexose compound selected from the group consisting of gum guar, pectin, algin, carboxymethylcellulose and mixtures of these and from 5 to parts by weight of a polyoxyethylene glycol selected from the group consisting of polyoxyethylene glycol having a molecular weight of from 200 to 6000.
3. Gum guar-polyoxyethylene glycol-400.
4. Gum guar-polyoxyethylene glycol-1000.
5. Gum guar-polyoxyethylene glycol-4000.
6. Gum guar-polyoxyethylene glycol-6000.
7. A compound comprising 4 parts by weight of polyoxyethylene glycol-400, 6 parts by Weight of polyoxyethylene g1yco1-1000 and 10 parts by weight of polyoxyethylene glycol-6000 and 2 parts by Weight of gum guar.
8. A compound comprising 16 parts by Weight of polyoxyethylene glycol-400 and 6 parts by weight of gum guar.
9. A compound comprising 7 parts by Weight of polyoxyethy1ene glycol-4000 and 3 parts by Weight of gum guar.
. Pectin-polyoxyethylene glycol-600*.
. Pectin-polyoxyethylene glycol-1000.
. Pectin-polyoxyethylene glycol-6000.
. Carboxymethylcellulose-polyoxyethylene glycol- Carboxymethylcellulose-po1yoxyethy1ene glycol- 15. Algin-polyoxyethylene glycol-400. 16. AIgin-polyoxyethylene glycol-6000.
References Cited UNITED STATES PATENTS Jeffries 167-63 Wimmer 260-209.5 Goyan et a1. 167--64 Gordon et a1. 167-63 Havemeyer 167-64 Otey et a1 260-21O Knoevenagel et a1. 260-210 Segal 260-209 15 LEWIS GOTTS, Primary Examiner.
RICHARD L. HUFF, JOHNNIE R. BROWN,
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|U.S. Classification||536/114, 536/2, 536/84, 536/3, 514/966|
|International Classification||A61K9/02, A61K9/00, C08G81/00, A61K47/36, C08B37/14, C08L1/28, C08B37/00|
|Cooperative Classification||A61K9/02, C08L1/28, Y10S514/966, C08B37/00, A61K47/36, C08G81/00, A61K9/0031, C08L5/00, C08L1/286, C08L5/04, C08L5/06|
|European Classification||C08L1/28, C08G81/00, C08B37/14D, C08B37/00, A61K9/02, A61K9/00M6, A61K47/36|