US2696456A - Dual element suppository - Google Patents
Dual element suppository Download PDFInfo
- Publication number
- US2696456A US2696456A US157746A US15774650A US2696456A US 2696456 A US2696456 A US 2696456A US 157746 A US157746 A US 157746A US 15774650 A US15774650 A US 15774650A US 2696456 A US2696456 A US 2696456A
- Authority
- US
- United States
- Prior art keywords
- coating
- core
- suppository
- water
- dispersible
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000000829 suppository Substances 0.000 title claims description 35
- 230000009977 dual effect Effects 0.000 title description 3
- 239000011248 coating agent Substances 0.000 claims description 71
- 238000000576 coating method Methods 0.000 claims description 71
- 239000000463 material Substances 0.000 claims description 25
- 239000003974 emollient agent Substances 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 239000007787 solid Substances 0.000 claims description 9
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 8
- 239000006185 dispersion Substances 0.000 claims description 8
- 239000000194 fatty acid Substances 0.000 claims description 8
- 229930195729 fatty acid Natural products 0.000 claims description 8
- 239000000155 melt Substances 0.000 claims description 7
- 210000001124 body fluid Anatomy 0.000 claims description 4
- 239000010839 body fluid Substances 0.000 claims description 4
- 150000004665 fatty acids Chemical class 0.000 claims description 4
- 150000005846 sugar alcohols Polymers 0.000 claims description 2
- 239000011162 core material Substances 0.000 description 54
- 229940110456 cocoa butter Drugs 0.000 description 21
- 235000019868 cocoa butter Nutrition 0.000 description 21
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 20
- 230000003444 anaesthetic effect Effects 0.000 description 20
- 229940100242 glycol stearate Drugs 0.000 description 19
- 229920001223 polyethylene glycol Polymers 0.000 description 18
- 239000002202 Polyethylene glycol Substances 0.000 description 17
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- 235000014150 Myroxylon pereirae Nutrition 0.000 description 13
- 244000302151 Myroxylon pereirae Species 0.000 description 13
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- 239000003026 cod liver oil Substances 0.000 description 10
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- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 5
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- 235000007173 Abies balsamea Nutrition 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 244000018716 Impatiens biflora Species 0.000 description 4
- 229910052797 bismuth Inorganic materials 0.000 description 4
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- 239000011253 protective coating Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- CFHQDOBIRREYNN-UHFFFAOYSA-M 1-methylpyridin-1-ium-2-carbaldehyde;chloride Chemical compound [Cl-].C[N+]1=CC=CC=C1C=O CFHQDOBIRREYNN-UHFFFAOYSA-M 0.000 description 3
- YQEMORVAKMFKLG-UHFFFAOYSA-N 2-stearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 239000004857 Balsam Substances 0.000 description 3
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- 230000037005 anaesthesia Effects 0.000 description 3
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- QXDAEKSDNVPFJG-UHFFFAOYSA-N phenacaine Chemical compound C1=CC(OCC)=CC=C1N\C(C)=N\C1=CC=C(OCC)C=C1 QXDAEKSDNVPFJG-UHFFFAOYSA-N 0.000 description 3
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- 239000000932 sedative agent Substances 0.000 description 3
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- 230000001225 therapeutic effect Effects 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 240000001879 Digitalis lutea Species 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 235000009470 Theobroma cacao Nutrition 0.000 description 2
- 239000002269 analeptic agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 description 2
- JAONZGLTYYUPCT-UHFFFAOYSA-K bismuth subgallate Chemical compound OC(=O)C1=CC(O)=C2O[Bi](O)OC2=C1 JAONZGLTYYUPCT-UHFFFAOYSA-K 0.000 description 2
- 229960000199 bismuth subgallate Drugs 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
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- 239000008199 coating composition Substances 0.000 description 2
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 229960002179 ephedrine Drugs 0.000 description 2
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- 238000009472 formulation Methods 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 235000019382 gum benzoic Nutrition 0.000 description 2
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- 239000003589 local anesthetic agent Substances 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- ZHALDANPYXAMJF-UHFFFAOYSA-N octadecanoate;tris(2-hydroxyethyl)azanium Chemical compound OCC[NH+](CCO)CCO.CCCCCCCCCCCCCCCCCC([O-])=O ZHALDANPYXAMJF-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- ANBFRLKBEIFNQU-UHFFFAOYSA-M potassium;octadecanoate Chemical compound [K+].CCCCCCCCCCCCCCCCCC([O-])=O ANBFRLKBEIFNQU-UHFFFAOYSA-M 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000003381 solubilizing effect Effects 0.000 description 2
- 229940029614 triethanolamine stearate Drugs 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- JNYAEWCLZODPBN-KVTDHHQDSA-N (2r,3r,4r)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@@H](O)[C@H]1O JNYAEWCLZODPBN-KVTDHHQDSA-N 0.000 description 1
- DSEKYWAQQVUQTP-XEWMWGOFSA-N (2r,4r,4as,6as,6as,6br,8ar,12ar,14as,14bs)-2-hydroxy-4,4a,6a,6b,8a,11,11,14a-octamethyl-2,4,5,6,6a,7,8,9,10,12,12a,13,14,14b-tetradecahydro-1h-picen-3-one Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)C(C)(C)CC[C@]1(C)CC[C@]2(C)[C@H]4CC[C@@]1(C)[C@H]3C[C@@H](O)C(=O)[C@@H]1C DSEKYWAQQVUQTP-XEWMWGOFSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- PWVUXRBUUYZMKM-UHFFFAOYSA-N 2-(2-hydroxyethoxy)ethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCOCCO PWVUXRBUUYZMKM-UHFFFAOYSA-N 0.000 description 1
- RZEWIYUUNKCGKA-UHFFFAOYSA-N 2-(2-hydroxyethylamino)ethanol;octadecanoic acid Chemical class OCCNCCO.CCCCCCCCCCCCCCCCCC(O)=O RZEWIYUUNKCGKA-UHFFFAOYSA-N 0.000 description 1
- MUHFRORXWCGZGE-KTKRTIGZSA-N 2-hydroxyethyl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCCO MUHFRORXWCGZGE-KTKRTIGZSA-N 0.000 description 1
- PUYOAVGNCWPANW-UHFFFAOYSA-N 2-methylpropyl 4-aminobenzoate Chemical compound CC(C)COC(=O)C1=CC=C(N)C=C1 PUYOAVGNCWPANW-UHFFFAOYSA-N 0.000 description 1
- VWZAGCZUPZKTET-UHFFFAOYSA-N 3-(dibutylamino)propyl 4-aminobenzoate;sulfuric acid Chemical compound OS(O)(=O)=O.CCCCN(CCCC)CCCOC(=O)C1=CC=C(N)C=C1.CCCCN(CCCC)CCCOC(=O)C1=CC=C(N)C=C1 VWZAGCZUPZKTET-UHFFFAOYSA-N 0.000 description 1
- AVGDKTGOMWQRNA-UHFFFAOYSA-N 3-methyl-5-pentan-2-ylphenol Chemical group CCCC(C)C1=CC(C)=CC(O)=C1 AVGDKTGOMWQRNA-UHFFFAOYSA-N 0.000 description 1
- HQFWVSGBVLEQGA-UHFFFAOYSA-N 4-aminobenzoic acid 3-(dibutylamino)propyl ester Chemical compound CCCCN(CCCC)CCCOC(=O)C1=CC=C(N)C=C1 HQFWVSGBVLEQGA-UHFFFAOYSA-N 0.000 description 1
- 241001106067 Atropa Species 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
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- DSDVUXRTYBTVRN-UHFFFAOYSA-N dimethyl(tetradecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCC[NH+](C)C DSDVUXRTYBTVRN-UHFFFAOYSA-N 0.000 description 1
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- 230000001804 emulsifying effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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- 239000003979 granulating agent Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930013053 morphinan alkaloid Natural products 0.000 description 1
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical class O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 1
- 229960005195 morphine hydrochloride Drugs 0.000 description 1
- XELXKCKNPPSFNN-BJWPBXOKSA-N morphine hydrochloride trihydrate Chemical compound O.O.O.Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O XELXKCKNPPSFNN-BJWPBXOKSA-N 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006218 nasal suppository Substances 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 150000002942 palmitic acid derivatives Chemical class 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- 229920000233 poly(alkylene oxides) Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229940114930 potassium stearate Drugs 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 1
- 229960001755 resorcinol Drugs 0.000 description 1
- WBHHMMIMDMUBKC-XLNAKTSKSA-N ricinelaidic acid Chemical compound CCCCCC[C@@H](O)C\C=C\CCCCCCCC(O)=O WBHHMMIMDMUBKC-XLNAKTSKSA-N 0.000 description 1
- 229960003656 ricinoleic acid Drugs 0.000 description 1
- FEUQNCSVHBHROZ-UHFFFAOYSA-N ricinoleic acid Natural products CCCCCCC(O[Si](C)(C)C)CC=CCCCCCCCC(=O)OC FEUQNCSVHBHROZ-UHFFFAOYSA-N 0.000 description 1
- NBFQYHKHPBMJJV-UHFFFAOYSA-N risocaine Chemical compound CCCOC(=O)C1=CC=C(N)C=C1 NBFQYHKHPBMJJV-UHFFFAOYSA-N 0.000 description 1
- CQRYARSYNCAZFO-UHFFFAOYSA-N salicyl alcohol Chemical compound OCC1=CC=CC=C1O CQRYARSYNCAZFO-UHFFFAOYSA-N 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
- JNMRHUJNCSQMMB-UHFFFAOYSA-N sulfathiazole Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CS1 JNMRHUJNCSQMMB-UHFFFAOYSA-N 0.000 description 1
- 229960001544 sulfathiazole Drugs 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- GSXRBRIWJGAPDU-BBVRJQLQSA-N tyrocidine A Chemical compound C([C@H]1C(=O)N[C@H](C(=O)N[C@@H](CCCN)C(=O)N[C@H](C(N[C@H](CC=2C=CC=CC=2)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N1)=O)CC(C)C)C(C)C)C1=CC=C(O)C=C1 GSXRBRIWJGAPDU-BBVRJQLQSA-N 0.000 description 1
- 229960003281 tyrothricin Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- RNWHGQJWIACOKP-UHFFFAOYSA-N zinc;oxygen(2-) Chemical compound [O-2].[Zn+2] RNWHGQJWIACOKP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
- A61K9/025—Suppositories; Bougies; Bases therefor; Ovules characterised by shape or structure, e.g. hollow layered, coated
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S424/00—Drug, bio-affecting and body treating compositions
- Y10S424/15—Suppositories
Definitions
- suppositories in general have been produced as a single unit containing oil-soluble and water-soluble materials in an oleaginous base.
- the suppositories have been found objectionable because of the adverse distribution coeflicient between the oleaginous base and the aqueous uid of the mucous surface of the area to be treated, the availability of the water-soluble constituents being reduced because the oleaginous constituents occlude the absorptive surfaces of the mucous membranes.
- Fig. 1 is a View partly in vertical section and partly in elevation showing a coated suppository embodying the improvements hereof and indicating principal constituents both of the core and of the coating;
- Fig.' 2 is a top plan view of the suppository of Fig. l as indicated by the line 2-2 of Fig. 1;
- Fig. 4 is a view partly in vertical section and partly in elevation of a completed suppository containing the core of Fig. 3;
- Fig. 5 is a plan view of the/suppository of Flg. 4.
- the suppository of this invention comprises a conical core 10 of a composition presently to be described, and having its conical face covered with a coating 12 of a composition also presently to be described.
- the core is a solid core, i. e., free from cavities.
- the tip of the coating 12 is preferably thickened somewhat so that the thickness thereof approximates about twice the thickness of the average coating applied directly to the conical wall of the core 10.
- the coating 12 steadily reduces in thickness as it extends from its tip to the base of the suppository, although a coating which is of uniform thickness between the tip and the base of the core is within the scope of the invention.
- the increased thickness at the tip of the conical structure compensates for increased time of contact of the tip with the body membranes of the patient as the suppository is introduced, and provides for an adequate supply of anesthetic and other agents'of the coating in order to insure quick action thereof throughout the extent of the body parts being treated.
- the core 10 is provided with a flanged base portion 10a whose frusto-conical walls are exposed and lie flush with the outer conical coating 12.
- its outer frusto-conical wall is provided with one or more longitudinally extended grooves 14 which, when the coating 12 is applied, are filled with integral extensions 12a of coating material. This arrangement facilitates application of the coating 12 to the core 10, and also provides a modicum of coating material at the locus of the core base 10a.
- the coating 12 comprises a water-dispersible base which is solid at normal room temperatures and completely disperses at body temperatures in the presence of body fluids.
- a water-dispersible base is desirably a glycol fatty acid ester, such as polyethylene glycol stearate, or the like, as more fully set out below.
- An essential agent contained in this outer coating 12 is a mild, nonirritatng, noninjurious, quick acting local anesthetic, of which propyl p-amino benzoate is the presently preferred form.
- tissue granulating agent of which urea is the presently preferred form.
- An acceptable composition for the outer coating is as follows:
- An improved coating will contain about 1% to 5% -of a tissue granulation agent, such as urea, for example 2.5%, above indicated. This will replace a corresponding proportion of the glycol stearate,
- the anesthetic material becomes immediately effective because the coating composition begins to disperse in the aqueous fluid of the mucosa immediately upon application of the suppository coating thereto.
- the tissue granulation agent is used, this also becomes immediately effective because of the water-dispersible character of the coating.
- both the anesthetic and the tissue granulation agent are adequately water-soluble to result in the desired immediate effect.
- an agent such as bismuth subgallate may be employed for this purpose, this material being appropriately used in percentages between about 3% and about 8% of the composition, for example 5%, corresponding proportions of the glycol stearate being replaced thereby.
- zinc oxide which also p ossesses antiseptic properties, may be used.
- An appropriate proportion of Zinc oxide would be about or between about 5% and 15 It is also desirable when zinc oxide is used vthat the proportion of the glycol stearate be correspondingly reduced.
- N-lauroyl colamino formylmethylpyridinium chloride which may be used in an amount between about 0.05% and 0.5%, for example, 0.1%
- the term is intended to include any such ester having a molecular weight in the order of 1,000 to 4,000, or those which tend to contain 10 to 40 ethylene groups.
- such glycol ester should be one having a melting point ranging between about 40 C. and 60 C., although the melting point of the coating, so long as it is high enough to withstand storage temperatures, is not critical because of the fact that even these higher melting-point esters disperse readily in the aqueous iiuids of the human body.
- a polyethylene glycol stearate having a molecular weight in the order of 1,000 to 1,500 is employed.
- composition of the suppository core this is made up of an emollient material having an appropriate melting point, namely, about 35.5 C., so that it is solid at normal room temperatures but will melt at body temperatures.
- This emollient preferably consists of or predominates in cocoa butter. When required to raise the melting somewhat, white beeswax is added in appropriate proportion.
- the dominating constituent of the core in addition to the emollient cocoa butter is balsam of Peru which is used to stimulate healing. Balsam of Peru may be employed in varying amounts between about 1% and 5% or 6%. for example 3%, the remainder of the composition being the emollient material such as cocoa butter.
- the core may consist of about 97% cocoa butter and 3% of balsam of Peru.
- an agent to solubilize the balsam of Peru in the cocoa butter This agent may be the water-dispersible glycol fatty acid ester above mentioned.
- 3% of balsam of Peru is employed, ap-
- acceptable core compositions are within the fol-.
- Emollient vehicle (cocoa butter) approximating 98.5%
- cod-liver oil may be used to provide an radditional healing emollient.
- cod-liver oil or between about 1% and 5% or 6% may be added, the cocoa In this f2.
- sucli a water-dispersible base acts also partially to emulsify the emollient materials of the core at the time the core melts, whereby the core readily releases its medicaments in the dispersion medium which resulted from the liquefaction of the outer coating.
- the highly preferable water-dispersible base is polyethylene glycol stearate.
- Substitutes may be polyethylene glycol oleate and laurate, ethylene glycol stearate, diethylene glycol stearate, glycerine monostearate, other stearic acid esters of glycerine, glycols or polymerized glycols, glycerine or glycol esters of other fatty acids than the stearic, oleic, and lauric acids above mentioned, such as palmitic, myristic, and similar fatty acids, derivatives of polyalkylene oxides, combined with castor oil, ricinoleic acid, oleyl alcohol, or the like, such as propylene oxide, ethylene oxide and similar cyclic oxides, or organic esters of polyhydric alcohols, such as mannitol, sorbitol, and dulcitol, or their anhydrides, such as mannitol, sorbitol, and dulcito
- the coating base may contain other appropriate emulsifying agents such as triethanolamine, triethanolamine stearate, sodium or potassium stearate, stearates of ethylamine and diethylamine, and monoethanolarnine and diethanolamine stearates, palmitates, and oleates.
- emulsifying agents such as triethanolamine, triethanolamine stearate, sodium or potassium stearate, stearates of ethylamine and diethylamine, and monoethanolarnine and diethanolamine stearates, palmitates, and oleates.
- propyl p-arnino benzoate is the highly preferred anesthetic for use in these suppositories, nevertheless, it is sometimes adequate to use one or more of the following: benzocaine (ethyl p-amino benzoate), isobutyl p-amino benzoate, laurocaine, procaine, phenacaine (holocaine), nupercaine, ephedrine, butacaine, tutocaine, and saligenin.
- the preferred material is the quaternary ammonium compound N-lauroyl colamino formylmethylpyridinium chloride, previously mentioned.
- quaternary ammonium salts such as cetyl trimethyl ammonium bromide, octadecenyl dimethyl benzyl ammonium bromide, p-tert-octylphenoxy ethoxy ethyl dimethyl benzyl ammonium chloride, 4-sulfonamidobenzyl tetradecyl dimethyl ammonium bromide.
- phenol potassium resorcin sulfonate, secondary amyltricresols, organic mercurials, oxyqniriolirie benzoate, ethyl m-amino p-hydroxybenzoate, hydroxy- As"above indicated, bismuth sub'gallate' is a.
- bismuth compound providingl'a v'me'chanicfal protective# coating action, but otherbismuth”compounds'oftenmay besed'such as bismuth subiodide', bismuth ji'Qdt'annate, and bismuth reso'rcinate.
- bismuth subiodide' bismuth ji'Qdt'annate
- bismuth reso'rcinate bismuth reso'rcinate.
- zinc' oxide has 'been i'nentioneclA as a preferred mildastr'inge'nt
- it soirietimes' will be acceptable to employ tannic acid, hamamelis, nutgall, extract'of belladonna, alum, and aluminum acetate.
- urea has been particularly mentio'nedoas 'the'prefer'able stimulating -agent for tissue granulation', it may sometimes be acceptable to substitute allantonin, ichthammal or kindred tissue granulation stimulating agent.v-
- cocoa butter hasv been employedpas the principal core vehicle be'cau'seof 'its emollie'nt, properties, and,l as has beenl pointed outy above, a' ,small vamount fof cod-liver oil may be added, if desired, because of its emol'- lientand healing action, lbeeswax being added in whatever amount is required to establish the' desired melting point of around 35.5 C.
- a small amount of emulsifying agent has'beenpadded' to allow for greater amounts of liquid to becomejinco'rporated inthe mass.
- emulsifying'agents which might be used for this purpose, but are usually less desirable, are triethanolamine stearate, glycerol monostearate', the sulfonated ester of dicarboxylic acid known as Aerosol OT, 'andLanettewax' SX, 'a British product which is'a mixture'of the higher fatty alcohols derived from the higher fatty acids by splitting'oil, such aslwhale or coconut oil, 'th'e' higher' 'fatty'alcoholsfbeing then .sulfated (th'e'S meanin'gsult'ated' and 'the 'X meaning '10% sulfated alcohol'pres'ent).
- anesthesia is created which relieves the pressurepain often caused by venous engorgement aggravatedby inflammatory'reaction of irritated sensory nerve endings.
- the anesthetic affords the'aggravated tissues the opportunity to retrogress to approximately normal and thereby preparesthe surfaces for the emollient action of the' medicated-core 'which subsequently melts at the Abody temperatures; Liquefaction and dispersion of the water-dispersible coating and its medicaments take place very quickly in the ano'rectal canal so that the anestheticand any otheningre'dients present comeimmediately into contact with the mucosal ⁇ Such immediate release of theY mildlocal anesthetic in the coating almost immediately reduces the discomfort of insertion.
- the ⁇ demulcent emollient and healing'medicamentsV ofthe 'low-'meltingpoint oleaginous core likewise becomereadily available to the tissues, especially since a degree of emulsiii'cation occurs whenthecore'melts and releases its ingredients in vthe dispersed'mediumwhich"resulted' from ytheliquefaction of the 'coatingmaterial"
- suppositories both with respect to the cores and the coatings thereof, as outlinedzabove, another as pectlis found inthe fact that the coatlngima'y be Vemployed onlyfor 'a fast4acting ⁇ pain relieving action',"andn the4 core employed 'only for an emollientaction.
- the core' may consist only of'cocoa butte or'coc'oa'butter with other emollients mentioned,'and ⁇ the c ""t'i'n'g'inay' coiisis't'onlyof thewaterdispersible' esters ',rner'itionedfsu'clr asmthe indicated polyethylene glycol stearate having a molecularweight around 1,500, andcontaining van appropriate'anesthe'tic.
- Analgesic type suppository Coating Percent Morphine hydrochloride (or sulphate) approximately Polyethylene glycol stearate do 99 Core:
- Vaginal type suppository Coating Percent Lactose approximately 25 Urea do 10 Phenylmercuric sulfathiazole do 10 Polyethylene glycol stearate do 55 Core:
- Nasal suppository Coating Percent Tyrothricin approximately Polyethylene glycol stearate do 94 Core:
- Ephedrine do 0.5 Beeswax do 17.5 Cocoa butter do 82.0
- a suppository comprising: a water-insoluble core which is solid at normal room temperatures and melts at normal body temperatures, said core comprising:
- said core comprising:
- a suppository comprising: an outer coating; and an inner core, said coating and core .having respectively approxlmately the following compositions:
- Guter coating Percent Antiseptic approximately 0.5 to l Anesthetic do l to 5 .0 Tissue-granulation stimulant do 1 to 10.0 Bismuth protective-coating compound do 2 to 10.0 Mild astringent do 5 to 15.0 Water-dispersible base do 65 to 98.0
- a suppository comprising: a core consisting essentially of a water-insoluble oily base which is solid at normal room temperatures, melts at body temperatures, and comprises an emollicnt vehicle and a medicament carried in said Vehicle; and an outer coating upon said core, said coating being solid at normal room temperatures, and dispersible at body temperatures in the body iluids, said coating comprising a water-dispersible material which is also a dispersion agent for said oily base, said material consisting of a higher fatty acid ester of a polyhydrc alcohol and being present in suicient quantity to substantially completely disperse all of the oily base of said core.
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Gynecology & Obstetrics (AREA)
- Medicinal Preparation (AREA)
Description
Dec. 7, 1954 R. D. HETTr-:RICK
DUAL ELEMENT sUPPosIToRY Filed April 24. 1950 2 .1..//a..........w.,..... .3. C. ....fuu...
vwithout exerting the desired therapeutic elfect. 'the drugs or medicaments are incorporated in a water- United States Patent O DUAL ELEMENT SUPPOSITORY Raymond Delos Hetterick, Chatham, N. J., assignor to The Lambert Company, Jersey City, N. J., a corporation of Delaware Application April 24, 1950, Serial No. 157,746
3 Claims. (Cl. 167-64) Vobject s to render the indicated anesthetic effects and action of the medicaments and emollient materials very much more rapid than has heretofore been possible.
It is another object of the invention to provide a suppository consisting essentially of two elements, one of which is an outer coating containing a mild local anesthetic in a carrier which disperses very rapidly in the body fluids so as to make the anesthetic material and medicaments immediately effective, and the other of which is an inner core which in turn provides for dispersion of healing emollient and other medicament materials, contained therein, immediately following dispersion of the coating material.
It is additionally an object of the invention to provide in such a suppository a water-dispersible coating containing the indicated anesthetic, the coating being readily dispersible in body fluids, and a water-insoluble, oil-soluble core which melts readily at body temperatures and carries the indicated medicaments and healing agents.
Heretofore suppositories in general have been produced as a single unit containing oil-soluble and water-soluble materials in an oleaginous base. The suppositories have been found objectionable because of the adverse distribution coeflicient between the oleaginous base and the aqueous uid of the mucous surface of the area to be treated, the availability of the water-soluble constituents being reduced because the oleaginous constituents occlude the absorptive surfaces of the mucous membranes.
It has also been found that many common therapeutic ,agents employed in the formulation of ordinary sup- `posltorles, particularly such insoluble compounds as zinc and bismuth salts, increase the viscosity of the oleaginous bases, thereby preventing ready liquefaction of the mass in the body orifice with the result that the medicaments may not be released, but may be held in the agglomerated mass of the suppositoryv and may, therefore., be excreted When soluble base type suppository, the demulcent and emollient action of the cocoa butter usually present is sacriiced, and the value thereof as an adjunct is thus limited.
However, the physio-chemical vehicle-medicament relationships as applied in the present suppository result in one which releases the medicaments to the tissues in proper sequence and the disadvantages and objections of the conventional types are overcome.
Other objects of the invention and the various features thereof will become apparent to those skilled in this art upon reference to the following specification and accompanying drawing wherein certain embodiments of the invention are disclosed.
ln the drawing:
Fig. 1 is a View partly in vertical section and partly in elevation showing a coated suppository embodying the improvements hereof and indicating principal constituents both of the core and of the coating;
Fig.' 2 is a top plan view of the suppository of Fig. l as indicated by the line 2-2 of Fig. 1;
2,696,456 Patented Dec. 7, 1954 ICC Fig. 3 is an elevation of a slightly modified form of core;
Fig. 4 is a view partly in vertical section and partly in elevation of a completed suppository containing the core of Fig. 3; and
Fig. 5 is a plan view of the/suppository of Flg. 4.
With particular reference to the drawing, the suppository of this invention comprises a conical core 10 of a composition presently to be described, and having its conical face covered with a coating 12 of a composition also presently to be described. As seen in Figs. 2 and 5 the core is a solid core, i. e., free from cavities. The tip of the coating 12 is preferably thickened somewhat so that the thickness thereof approximates about twice the thickness of the average coating applied directly to the conical wall of the core 10. Desirably, the coating 12 steadily reduces in thickness as it extends from its tip to the base of the suppository, although a coating which is of uniform thickness between the tip and the base of the core is within the scope of the invention. The increased thickness at the tip of the conical structure compensates for increased time of contact of the tip with the body membranes of the patient as the suppository is introduced, and provides for an adequate supply of anesthetic and other agents'of the coating in order to insure quick action thereof throughout the extent of the body parts being treated.
In the form of the suppository of Figs. 3, 4, and 5, the core 10 is provided with a flanged base portion 10a whose frusto-conical walls are exposed and lie flush with the outer conical coating 12. Preferably, where the base portion 10a is employed, its outer frusto-conical wall is provided with one or more longitudinally extended grooves 14 which, when the coating 12 is applied, are filled with integral extensions 12a of coating material. This arrangement facilitates application of the coating 12 to the core 10, and also provides a modicum of coating material at the locus of the core base 10a.
Principally, the coating 12 comprises a water-dispersible base which is solid at normal room temperatures and completely disperses at body temperatures in the presence of body fluids. Such a water-dispersible base is desirably a glycol fatty acid ester, such as polyethylene glycol stearate, or the like, as more fully set out below. An essential agent contained in this outer coating 12 is a mild, nonirritatng, noninjurious, quick acting local anesthetic, of which propyl p-amino benzoate is the presently preferred form.
Another very desirable agent to be employed in the coating is a tissue granulating agent of which urea is the presently preferred form.
An acceptable composition for the outer coating, at least for some purposes, is as follows:
An improved coating will contain about 1% to 5% -of a tissue granulation agent, such as urea, for example 2.5%, above indicated. This will replace a corresponding proportion of the glycol stearate,
As has been indicated above, by using a water-dispersible coating base, such as the indicated' glycol stearate or an equivalent glycol fatty acid ester, or the like, the anesthetic material becomes immediately effective because the coating composition begins to disperse in the aqueous fluid of the mucosa immediately upon application of the suppository coating thereto. Similarly, where the tissue granulation agent is used, this also becomes immediately effective because of the water-dispersible character of the coating. Obviously both the anesthetic and the tissue granulation agent are adequately water-soluble to result in the desired immediate effect.
In the event that a mechanical protective coating effect is desired, as is commonly the case, an agent such as bismuth subgallate may be employed for this purpose, this material being appropriately used in percentages between about 3% and about 8% of the composition, for example 5%, corresponding proportions of the glycol stearate being replaced thereby. Similarly, should an astringent be required, as is commonly desirable, zinc oxide, which also p ossesses antiseptic properties, may be used. An appropriate proportion of Zinc oxide would be about or between about 5% and 15 It is also desirable when zinc oxide is used vthat the proportion of the glycol stearate be correspondingly reduced.
In practical use, it has been found clinically desirable to incorporate a minor but adequate proportion of an antiseptic material which has local bactericidal action and will inhibit contamination. One Very satisfactory and preferred agent for this purpose is N-lauroyl colamino formylmethylpyridinium chloride which may be used in an amount between about 0.05% and 0.5%, for example, 0.1%
Substitutes which are usable, at least for some purposes, for various coating constituents above mentioned will be discussed more fully hereinafter.
As to the polyethylene glycol stearate employed, the term is intended to include any such ester having a molecular weight in the order of 1,000 to 4,000, or those which tend to contain 10 to 40 ethylene groups. 1n general, for the coating composition such glycol ester should be one having a melting point ranging between about 40 C. and 60 C., although the melting point of the coating, so long as it is high enough to withstand storage temperatures, is not critical because of the fact that even these higher melting-point esters disperse readily in the aqueous iiuids of the human body. Commonly a polyethylene glycol stearate having a molecular weight in the order of 1,000 to 1,500 is employed.
With respect to the composition of the suppository core, this is made up of an emollient material having an appropriate melting point, namely, about 35.5 C., so that it is solid at normal room temperatures but will melt at body temperatures. This emollient preferably consists of or predominates in cocoa butter. When required to raise the melting somewhat, white beeswax is added in appropriate proportion. Ordinarily the dominating constituent of the core in addition to the emollient cocoa butter is balsam of Peru which is used to stimulate healing. Balsam of Peru may be employed in varying amounts between about 1% and 5% or 6%. for example 3%, the remainder of the composition being the emollient material such as cocoa butter. In other words, the core may consist of about 97% cocoa butter and 3% of balsam of Peru. However, it is ordinarily desirable, if not necessary, to include an agent to solubilize the balsam of Peru in the cocoa butter. This agent may be the water-dispersible glycol fatty acid ester above mentioned. Where 3% of balsam of Peru is employed, ap-
proximately 3% of the glycol ester is used, this varying between about 0.5% and 5% as the balsam varies. Addition of this material correspondingly reduces the emollient cocoa butter content. Thus, acceptable core compositions, at least for some purposes, are within the fol-.
lowing:
Balsam of Peru approximating 1.0% to 5% or 6%. Solubilizer approximating 0.5% to 4% or 5%.
Emollient vehicle (cocoa butter) approximating 98.5%
If required or deemed necessary, small proportions of cod-liver oil may be used to provide an radditional healing emollient. Thus, about 2.5 of cod-liver oil, or between about 1% and 5% or 6% may be added, the cocoa In this f2.
a Range percent Balsam of Peru approximating 3.0% 1.0 to 5 Polyethylene glycol stearate (solubilizer for balsam of Peru) approximating 2.0% 0.5 to 4 Cod-liver oil (healing emollient) approximating 2.5% 1.0 to 5 Beeswax approximating 17.5% 15.0 to 30 Cocoa butter approximating 75.0% 87.5 to 56 In combination with a core having a melting point of 35 C. to 36 C., as above indicated, a very effective ,coating having an appropriate melting point (e. g. 45 C.
to C.) is the following (optimum range also given);
Range percent N-lauroyl colamino formylmethyl-pyridiniuin Zinc oxide (astringent) approximating 10.0%" 5.0 to 10 Polyethylene glycol stearate (water-dispersible base) approximating 80.4% to 66 In using the above coating and core compositions, it will be apparent that the water-dispersible coating first disperses in the body iiuids and makes the anesthetic and also the tissue granulation agent, if used, immediately effective. Similarly, any other of the above-mentioned coating agents, if used in the coating, become `promptly eiective. After dispersion of the coating, the water-insoluble core material then begins to melt, so that the balsam of Peru or similar healing agent becomes promptly effective along with the melted emollient cocoa butter with or without cod-liver oil or the like.
Where a water-dispersible agent is used in the coating which is appropriate to solubilize the balsam of Peru, sucli a water-dispersible base acts also partially to emulsify the emollient materials of the core at the time the core melts, whereby the core readily releases its medicaments in the dispersion medium which resulted from the liquefaction of the outer coating.
From the standpoint of materials which may be eniployed, at least for some uses, as substitutes for the much preferred agents above discussed, the following data are given.
In the outer coating, as has been pointed out above, the highly preferable water-dispersible base is polyethylene glycol stearate. Substitutes, as above indicated, may be polyethylene glycol oleate and laurate, ethylene glycol stearate, diethylene glycol stearate, glycerine monostearate, other stearic acid esters of glycerine, glycols or polymerized glycols, glycerine or glycol esters of other fatty acids than the stearic, oleic, and lauric acids above mentioned, such as palmitic, myristic, and similar fatty acids, derivatives of polyalkylene oxides, combined with castor oil, ricinoleic acid, oleyl alcohol, or the like, such as propylene oxide, ethylene oxide and similar cyclic oxides, or organic esters of polyhydric alcohols, such as mannitol, sorbitol, and dulcitol, or their anhydrides, such as mannitan, sorbita'n and dulcitan. If required, the coating base may contain other appropriate emulsifying agents such as triethanolamine, triethanolamine stearate, sodium or potassium stearate, stearates of ethylamine and diethylamine, and monoethanolarnine and diethanolamine stearates, palmitates, and oleates.
From the standpoint of the anesthetic, this must be nonirritating upon application, must create anesthesia without damage to nerve structure, must have a low systemic toxicity, and must possess rapidity of onset of anesthesia. While the above-mentioned propyl p-arnino benzoate is the highly preferred anesthetic for use in these suppositories, nevertheless, it is sometimes adequate to use one or more of the following: benzocaine (ethyl p-amino benzoate), isobutyl p-amino benzoate, laurocaine, procaine, phenacaine (holocaine), nupercaine, ephedrine, butacaine, tutocaine, and saligenin. These materials are employed in their respective appropriate foi-nis including the sulfates and hydrochlorides, as the case may be. Where butacaine sulfate, tutocaine hydrochloride, and holocaine are employed, it will be necessary, due to insolubility in the coating material, to disperse them in the molten coating and maintain even dispersion thereof during production of the suppository.
With reference to the antiseptic which may be used in the coating, the preferred material is the quaternary ammonium compound N-lauroyl colamino formylmethylpyridinium chloride, previously mentioned. However, it is possible to use other quaternary ammonium salts, such as cetyl trimethyl ammonium bromide, octadecenyl dimethyl benzyl ammonium bromide, p-tert-octylphenoxy ethoxy ethyl dimethyl benzyl ammonium chloride, 4-sulfonamidobenzyl tetradecyl dimethyl ammonium bromide. For appropriate uses one or more of the following may be employed: phenol, potassium resorcin sulfonate, secondary amyltricresols, organic mercurials, oxyqniriolirie benzoate, ethyl m-amino p-hydroxybenzoate, hydroxy- As"above indicated, bismuth sub'gallate' is a. preferred bismuth compound providingl'a v'me'chanicfal protective# coating action, but otherbismuth"compounds'oftenmay besed'such as bismuth subiodide', bismuth ji'Qdt'annate, and bismuth reso'rcinate.',"' Where zinc' oxide has 'been i'nentioneclA as a preferred mildastr'inge'nt," it soirietimes' will be acceptable to employ tannic acid, hamamelis, nutgall, extract'of belladonna, alum, and aluminum acetate. Where urea 'has been particularly mentio'nedoas 'the'prefer'able stimulating -agent for tissue granulation', it may sometimes be acceptable to substitute allantonin, ichthammal or kindred tissue granulation stimulating agent.v-
Inuthewcore, cocoa butter hasv been employedpas the principal core vehicle be'cau'seof 'its emollie'nt, properties, and,l as has beenl pointed outy above, a' ,small vamount fof cod-liver oil may be added, if desired, because of its emol'- lientand healing action, lbeeswax being added in whatever amount is required to establish the' desired melting point of around 35.5 C. In order to increase the area of contactA and increase the drug exchange between' fluids of the mucosa and both the soluble and insoluble drugs a small amount of emulsifying agent"has'beenpadded' to allow for greater amounts of liquid to becomejinco'rporated inthe mass. As previously pointed out, 'around 1% of polyethylene glycol stearate has'b'ee'n added" tothe core, thereby .performing '-both'the'action just mentioned and solubilizing the balsam' of'Peru.'" Other emulsifying'agents which might be used for this purpose, but are usually less desirable, are triethanolamine stearate, glycerol monostearate', the sulfonated ester of dicarboxylic acid known as Aerosol OT, 'andLanettewax' SX, 'a British product which is'a mixture'of the higher fatty alcohols derived from the higher fatty acids by splitting'oil, such aslwhale or coconut oil, 'th'e' higher' 'fatty'alcoholsfbeing then .sulfated (th'e'S meanin'gsult'ated' and 'the 'X meaning '10% sulfated alcohol'pres'ent).
The use of both cod-liver oil and balsam of Peru in theI lindicated amounts supplies to the suppository the healing effects'of'both'ofthese'agents; IfA desired, a small amount of'castor oil, 'for 'example' yabout 2%, may be used as a means for solubilizing the balsa'm ofV Peru', these being, combined before incorporation'int'o'the core mass. Byv thismeans the' balsamof Peru is preventedfrom'separating out". Otherwise, the:above-mentined'jsmall proportion of polyethylene glycol stearatemay'beus'ed alone orin addition t'o the castor'oil;y
Respecting balsamof Peru, whichisusedbecauseof its l.
abilityto stimulate local resistancezinthetissuesand a tendency to exert a `protective action, as well as a mild bactericidal action, no whollyfsatisfactory substituterhas been found, but partial'satisfaction may be obtained'from balsams oftolu, benzoin and storax, myi'rh and 'tyroy Substitutes sometimes` usable"instead"of"beesthricin. wax are paraflin (about 509 C.' 'll/i. ,P.),' spermac'eti, carnauba wax', ceresin,' o zokerite vand polyethylene glycols having higher molecular weights in the rang'ei from about 1,500 to 4,000 with melting points of about 40 C. to ",C., togetherT with-previously indicated esters of such glycols. ,L a H In the light of the above `outline of Various compositions Yof the inner core and the outer coating, a general rangeof the various materials indicated in eachl element rNNEnCoREv Solubilizer, approximately 0.5% to 5%, e. g. 3.0%. Cod-liver oil, approximately 0.0% to 5 e. g. 2.5%. Balsam' of Peru, approximately 1.0% to 5 e. g.-f3.0%. Beeswax, approximatelyl 0.0% to 30%, e. g. 17.45%. Cocoa butter,t approximately 98.5 %'to65%.`
Expanding on the function:of th'eytwofpaits rof'the'present suppository, the purpose, as has been pointed out heresurfaces.
after furthertot'reat' "the mucosa 'by a somewhat difef ent type of ,composition. `In the treatment of hembr' rh'idls4 and anorectal; conditions, various" painful condi tions' commonly exist such asA abrasionsj traum'ati'sm offf the mucosar of the canal, minute breaks mthe vein walls;
or spongyand granular" conditions' of the mucosa, even to the' exent that laceration" may 'exist and ulcerationoccur infthe'presence ofA infective iior'a;4 It is desirable,"there'gl fore',`to cause the supposito'ry to alleviate the pain' 'ofiiintrol duction under conditions` such as above indicated,jand' prepare the surfaces "for' treatment by further'medcaments, whereby successive 'therapeutic effects are obtained because` of specific characteristics of the successivelj/"availableagents. j l
It isL also desirbleto'errploy a mild astringent',fs uchj as the zinc oxide andsimilar n'iat'erials,p'ireviously'y mentioned, and also to use one` of the' bismuth compounds to 'provide' the' mechanical protective-coating' action mentioned.' However, employmentY of substances 'such as Zinc 'oxide and the bismuth compounds tends to raise the melting point of the water-insoluble emollient materialgsuchfas cocoa butter, required. It is therefore an' important feature of this invention that-'the zinc oxide-'or other astringent and the bismuth compound are `carried in'the water-dispersible -base of the outer coating-Which also carries the anesthetic and the antiseptic when usedn' Thus, not`only `is the local topical anesthetic keffective in the coating to allay pain and to relax the sphincter spas/m, when the easy passage' ofstools'is "sought, but the astringent and protective-coating materials are made'favail able in the'quickly liqueabl'e wate'rdispersible coating material without vthe possibility of having any effect upon the"melting point-or' the core material. Furtherg'by the incorporation of the anesthetic in the water-dispersible base of the"coating,a controlled mild surface: anesthesia is created which relieves the pressurepain often caused by venous engorgement aggravatedby inflammatory'reaction of irritated sensory nerve endings. By the prompt action of the anesthetic zupon'they nerve'endings through rapid dispersion of the water-dispersible coating, the anesthetic affords the'aggravated tissues the opportunity to retrogress to approximately normal and thereby preparesthe surfaces for the emollient action of the' medicated-core 'which subsequently melts at the Abody temperatures; Liquefaction and dispersion of the water-dispersible coating and its medicaments take place very quickly in the ano'rectal canal so that the anestheticand any otheningre'dients present comeimmediately into contact with the mucosal `Such immediate release of theY mildlocal anesthetic in the coating almost immediately reduces the discomfort of insertion. Uponexp'osure of the core following liquefaction of the coating, the `demulcent emollient and healing'medicamentsV ofthe 'low-'meltingpoint oleaginous core likewise becomereadily available to the tissues, especially since a degree of emulsiii'cation occurs whenthecore'melts and releases its ingredients in vthe dispersed'mediumwhich"resulted' from ytheliquefaction of the 'coatingmaterial" In addition to the :preferred forms of suppositories, both with respect to the cores and the coatings thereof, as outlinedzabove, another as pectlis found inthe fact that the coatlngima'y be Vemployed onlyfor 'a fast4acting`pain relieving action',"andn the4 core employed 'only for an emollientaction. In such a case, the core'may consist only of'cocoa butte or'coc'oa'butter with other emollients mentioned,'and` the c ""t'i'n'g'inay' coiisis't'onlyof thewaterdispersible' esters ',rner'itionedfsu'clr asmthe indicated polyethylene glycol stearate having a molecularweight around 1,500, andcontaining van appropriate'anesthe'tic. Thus,
Vfor rapid anesthetic action the' coating would contain 4about 2%' of the' mentioned propyl p-amino` benz'oatewhre prolonged effect is not 'requiredor' a's'much as 5%"of 'such anesthetic when a prolonged effect isnec'e'ssary.I For ulclh usesA suppository compositionsmay be 'tabulated as o ows:
CORE' Percent Cocoabutter (with or without otheremollients) COATING Thus, themsuppository) of'this invention' is safe .for-use as a pallratlve and for adJunctive treatment even for rela- Sedative type suppository This type of suppository may be employed Where a quick-acting sedative is required followed by a prolonging effect from a slower acting sedative. For this purpose a water-soluble substance is placed in the coating and a solvent-soluble type incorporated in the core, thus allowing a synergistic action to take place between the two.
Coating: Percent Pentobarbital sodium approximately 3 Polyethylene glycol stearate do 97 Core:
Phenobarbital do 5.5
Beeswax do 17.5
Cocoa butter do 77 .0
Analgesic type suppository Coating: Percent Morphine hydrochloride (or sulphate) approximately Polyethylene glycol stearate do 99 Core:
Morphine alkaloid do 1.5
Beeswax do 17.5
Cocoa butter do 81.0
Vaginal type suppository Coating: Percent Lactose approximately 25 Urea do 10 Phenylmercuric sulfathiazole do 10 Polyethylene glycol stearate do 55 Core:
Menthol do 2.0
Cod-liver oil do 2.5
Beeswax do 17.5
Cocoa butter do 78.0
Digitalis suppository Coating: Percent Digitoxin approximately 0-.1 Polyethylene glycol stearate do 99.9
Core:
Digitalis leaf do 5.5
Beeswax do 17.5
Cocoa butter do 77.0
Nasal suppository Coating: Percent Tyrothricin approximately Polyethylene glycol stearate do 94 Core:
Ephedrine do 0.5 Beeswax do 17.5 Cocoa butter do 82.0
In all of the above specific formulations, it will be noted that incorporated in the coating material are the quick-acting, water-soluble medicaments and in the oleaginous core are placed the medicaments which yield either prolonged action or demulcent eiects, or sustain the mode of therapy used.
From the foregoing it will be apparent that I have presented a novel type of suppository for many uses, which, in its broadest aspect relies on a water-dispersible coating adapted to carry various medicaments for initial etect upon the mucosa, and a water-insoluble emollient core adapted to carry Various medicaments, which may be subsequently dispersed or solubilized by the agency of the dispersed coating, whereby the emollient and/or medicament effects of the core become eifective following the initial effect, such as an anesthetic effect, of the coating.
Inasmuch as modifications of the generic invention herein disclosed will no doubt occur to those skilled in this art, it is intended to protect all such variations as fall within the scope of the patent claims.
I claim as my invention:
1. A suppository comprising: a water-insoluble core which is solid at normal room temperatures and melts at normal body temperatures, said core comprising:
Percent Balsam of Peru approximately 3.0 Polyethylene glycol stearate do 2.0 Cod-liver oil do 2.5 Beeswax do 17.5 Cocoa butter do 75.0
and a coating upon said core, said coating being solid at normal room temperatures and being dispersible in body uids, said core comprising:
Percent N-lauroyl colamino formylmethyl-pyridinium chlo ride approximately 0.1 Propyl amino benzoate do 2.0 Urea do 2.5 Bismuth subgallate do 5.0 Zinc oxide do 10.0 Polyethylene glycol stearate do 80.4
2. A suppository comprising: an outer coating; and an inner core, said coating and core .having respectively approxlmately the following compositions:
Guter coating: Percent Antiseptic approximately 0.5 to l Anesthetic do l to 5 .0 Tissue-granulation stimulant do 1 to 10.0 Bismuth protective-coating compound do 2 to 10.0 Mild astringent do 5 to 15.0 Water-dispersible base do 65 to 98.0
Inner core:
Solubilizer do 0.5 to 5 Cod-liver oil do 1 to 5 Balsam of Peru do 1.0 to 5 Beeswax do 15 to 30 Cocoa butter do 98.5 to 56 3. A suppository comprising: a core consisting essentially of a water-insoluble oily base which is solid at normal room temperatures, melts at body temperatures, and comprises an emollicnt vehicle and a medicament carried in said Vehicle; and an outer coating upon said core, said coating being solid at normal room temperatures, and dispersible at body temperatures in the body iluids, said coating comprising a water-dispersible material which is also a dispersion agent for said oily base, said material consisting of a higher fatty acid ester of a polyhydrc alcohol and being present in suicient quantity to substantially completely disperse all of the oily base of said core.
References Cited in the le of this patent UNITED STATES PATENTS Number Name Date 2,020,107 Cruickshank Nov. 5, 1935 2,055,063 Bird Sept. 22, 1936 2,142,537 Tisza Jan. 3, 1939 2,191,139 Bibbins Feb. 20, 1940 2,241,331 Shelton May 6, 1941 2,473,368 Flintermann June 14, 1949 2,477,292 Fesserrden Iuly 26, 1949 2,538,127 Saunders Jan. 16, 1951i FOREIGN PATENTS i Number Country Date 613,310 Germany May 16, 1935 648,690 Germany Aug. 6, 1937 549,466 Germany July 26, 1932 630,608 Germany June 2, 1936 OTHER REFERENCES Wood et al., The Dispensatory of the U. S., 23rd Ed., 1943, I. P. Lippincott, Phila., p. 920.
Remingtons Practise of Pharmacy, 9th Ed. p. 451, Mack Publ. Co., 1950, Easton, Pa.
Claims (1)
- 3. A SUPPOSITORY COMPRISING: A CORE CONSISTING ESSENTIALLY OF A WATER-INSOLUBLE OILY BASE WHICH IS SOLID AT NORMAL ROOM TEMPERATURES, MELTS AT BODY TEMPERATURES, AND COMPRISES AN EMOLLIENT VEHICLE AND A MEDICAMENT CARRIED IN SAID VEHICLE; AND AN OUTER COATING UPON SAID CORE, SAID COATING BEING SOLID AT NORMAL ROOM TEMPERATURES, AND DISPERSIBLE AT BODY TEMPERATURES IN THE BODY FLUIDS, SAID COATING COMPRISING A WATER-DISPERSIBLE MATERIAL WHICH IS ALSO A DISPERSION AGENT FOR SAID OILY BASE, SAID MATERIAL CONSISTING OF A HIGHER FATTY ACID ESTER OF A POLYHYDRIC ALCOHOL AND BEING PRESENT IN SIFFICIENT QUANTITY TO SUBSTANTIALLY COMPLETELY DISPERSE ALL OF THE OILY BASE OF SAID CORE.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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US157746A US2696456A (en) | 1950-04-24 | 1950-04-24 | Dual element suppository |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US157746A US2696456A (en) | 1950-04-24 | 1950-04-24 | Dual element suppository |
Publications (1)
Publication Number | Publication Date |
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US2696456A true US2696456A (en) | 1954-12-07 |
Family
ID=22565086
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US157746A Expired - Lifetime US2696456A (en) | 1950-04-24 | 1950-04-24 | Dual element suppository |
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US (1) | US2696456A (en) |
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US3343540A (en) * | 1964-04-27 | 1967-09-26 | Frederick P Siegel | Swab-type applicator with impregnated medicament |
US3415249A (en) * | 1966-01-07 | 1968-12-10 | Stanley Drug Products Inc | Suppository |
US3443563A (en) * | 1966-08-29 | 1969-05-13 | Atsumi Ishihama | Vaginal suppository |
US3496938A (en) * | 1966-08-18 | 1970-02-24 | Eisai Co Ltd | Contraceptive membranes and preparation thereof |
US3929132A (en) * | 1973-04-10 | 1975-12-30 | Alza Corp | Osmotic dispenser |
US4344968A (en) * | 1978-12-09 | 1982-08-17 | Nippon Kayaku Kabushiki Kaisha | Pharmaceutical vehicle |
US4892890A (en) * | 1984-11-01 | 1990-01-09 | G. D. Searle And Company | External analgesic compositions |
US5480644A (en) * | 1992-02-28 | 1996-01-02 | Jsf Consultants Ltd. | Use of injectable biomaterials for the repair and augmentation of the anal sphincters |
US20030191070A1 (en) * | 2000-06-06 | 2003-10-09 | Kinuko Oku | Medical composition kit for treating lesioned abnormal tissue |
US20070128254A1 (en) * | 2005-12-07 | 2007-06-07 | Heuer Daniel J | Methods of attaching a dosage form to a medicated tampon assembly |
WO2007078402A2 (en) * | 2005-12-15 | 2007-07-12 | Kimberly-Clark Worldwide, Inc. | A layered dosage form for a medicated tampon assembly |
US7527614B2 (en) | 2005-03-25 | 2009-05-05 | Kimberly-Clark Worldwide, Inc. | Protective tube for a medicated tampon |
US7708726B2 (en) | 2005-04-28 | 2010-05-04 | Kimberly-Clark Worldwide, Inc. | Dosage form cap for an applicator |
US7744556B2 (en) | 2005-03-25 | 2010-06-29 | Kimberly-Clark Worldwide, Inc. | Delivery tube assembly for an applicator |
US7919453B2 (en) | 2005-03-25 | 2011-04-05 | Kimberly-Clark Worldwide, Inc. | Dosage cap assembly for an applicator |
US7993667B2 (en) | 2005-03-25 | 2011-08-09 | Kimberly-Clark Worldwide, Inc. | Methods of manufacturing a medicated tampon assembly |
WO2013035113A1 (en) | 2011-09-06 | 2013-03-14 | Lipid Pharmaceuticals Ehf. | Coated suppositories |
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DE549466C (en) * | 1930-06-28 | 1932-07-26 | Albert Mendel Akt Ges | suppository |
DE613310C (en) * | 1930-11-28 | 1935-05-16 | August Karreth | Process for the production of foam-developing preparations |
DE630608C (en) * | 1933-10-20 | 1936-06-02 | Gustav Rost Dr | Process for the production of a water-soluble, easily absorbable and diffusible base material for suppositories |
US2020107A (en) * | 1934-08-06 | 1935-11-05 | George A Cruickshank | Combination pessary and vaginal suppository |
US2055063A (en) * | 1935-11-25 | 1936-09-22 | Hoffmann La Roche | Suppository medication |
US2142537A (en) * | 1936-07-22 | 1939-01-03 | Rare Chemicals Inc | Anesthetic ointment |
US2191139A (en) * | 1938-03-14 | 1940-02-20 | Lilly Co Eli | Suppository |
US2241331A (en) * | 1939-01-27 | 1941-05-06 | Wm S Merrell Co | Suppository |
US2473368A (en) * | 1944-02-25 | 1949-06-14 | Flintermann Gerhard | Suppository |
US2477292A (en) * | 1946-10-11 | 1949-07-26 | Wyeth Corp | Polyvinyl-alcohol-coated suppository |
US2538127A (en) * | 1948-02-26 | 1951-01-16 | Searle & Co | Medicated suppositories and bases therefor |
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3122475A (en) * | 1960-02-25 | 1964-02-25 | Schaeppi Ag Dr | Circulatory adjuvant shell elements for cardiac glycoside suppository cores |
US3343540A (en) * | 1964-04-27 | 1967-09-26 | Frederick P Siegel | Swab-type applicator with impregnated medicament |
US3415249A (en) * | 1966-01-07 | 1968-12-10 | Stanley Drug Products Inc | Suppository |
US3496938A (en) * | 1966-08-18 | 1970-02-24 | Eisai Co Ltd | Contraceptive membranes and preparation thereof |
US3443563A (en) * | 1966-08-29 | 1969-05-13 | Atsumi Ishihama | Vaginal suppository |
US3929132A (en) * | 1973-04-10 | 1975-12-30 | Alza Corp | Osmotic dispenser |
US4344968A (en) * | 1978-12-09 | 1982-08-17 | Nippon Kayaku Kabushiki Kaisha | Pharmaceutical vehicle |
US4892890A (en) * | 1984-11-01 | 1990-01-09 | G. D. Searle And Company | External analgesic compositions |
US5480644A (en) * | 1992-02-28 | 1996-01-02 | Jsf Consultants Ltd. | Use of injectable biomaterials for the repair and augmentation of the anal sphincters |
US5490984A (en) * | 1992-02-28 | 1996-02-13 | Jsf Consulants Ltd. | Use of injectable biomaterials for the repair and augmentation of the anal sphincters |
US20030191070A1 (en) * | 2000-06-06 | 2003-10-09 | Kinuko Oku | Medical composition kit for treating lesioned abnormal tissue |
US7381419B2 (en) * | 2000-06-06 | 2008-06-03 | Lequio Pharma Co., Ltd. | Medical composition kit for treating lesioned abnormal tissue |
US7527614B2 (en) | 2005-03-25 | 2009-05-05 | Kimberly-Clark Worldwide, Inc. | Protective tube for a medicated tampon |
US7744556B2 (en) | 2005-03-25 | 2010-06-29 | Kimberly-Clark Worldwide, Inc. | Delivery tube assembly for an applicator |
US7919453B2 (en) | 2005-03-25 | 2011-04-05 | Kimberly-Clark Worldwide, Inc. | Dosage cap assembly for an applicator |
US7993667B2 (en) | 2005-03-25 | 2011-08-09 | Kimberly-Clark Worldwide, Inc. | Methods of manufacturing a medicated tampon assembly |
US8388996B2 (en) | 2005-03-25 | 2013-03-05 | Kimberly-Clark Worldwide, Inc. | Methods of manufacturing a medicated tampon assembly |
US7708726B2 (en) | 2005-04-28 | 2010-05-04 | Kimberly-Clark Worldwide, Inc. | Dosage form cap for an applicator |
US20070128254A1 (en) * | 2005-12-07 | 2007-06-07 | Heuer Daniel J | Methods of attaching a dosage form to a medicated tampon assembly |
WO2007078402A2 (en) * | 2005-12-15 | 2007-07-12 | Kimberly-Clark Worldwide, Inc. | A layered dosage form for a medicated tampon assembly |
WO2007078402A3 (en) * | 2005-12-15 | 2007-08-30 | Kimberly Clark Co | A layered dosage form for a medicated tampon assembly |
WO2013035113A1 (en) | 2011-09-06 | 2013-03-14 | Lipid Pharmaceuticals Ehf. | Coated suppositories |
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