US3454697A - Tetracycline antibiotic compositions for oral use - Google Patents
Tetracycline antibiotic compositions for oral use Download PDFInfo
- Publication number
- US3454697A US3454697A US462407A US3454697DA US3454697A US 3454697 A US3454697 A US 3454697A US 462407 A US462407 A US 462407A US 3454697D A US3454697D A US 3454697DA US 3454697 A US3454697 A US 3454697A
- Authority
- US
- United States
- Prior art keywords
- antibiotics
- antibiotic
- dmct
- tetracycline
- oral use
- 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
- 239000000203 mixture Substances 0.000 title description 23
- 229940072172 tetracycline antibiotic Drugs 0.000 title description 4
- 239000003242 anti bacterial agent Substances 0.000 description 27
- 229940088710 antibiotic agent Drugs 0.000 description 25
- 230000000844 anti-bacterial effect Effects 0.000 description 24
- 230000003115 biocidal effect Effects 0.000 description 20
- 239000004098 Tetracycline Substances 0.000 description 15
- 235000019364 tetracycline Nutrition 0.000 description 15
- 150000003522 tetracyclines Chemical class 0.000 description 15
- GUXHBMASAHGULD-SEYHBJAFSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1([C@H]2O)=C(Cl)C=CC(O)=C1C(O)=C1[C@@H]2C[C@H]2[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]2(O)C1=O GUXHBMASAHGULD-SEYHBJAFSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 12
- 230000003385 bacteriostatic effect Effects 0.000 description 9
- 229940040944 tetracyclines Drugs 0.000 description 9
- 239000002775 capsule Substances 0.000 description 7
- 210000002966 serum Anatomy 0.000 description 7
- 239000006188 syrup Substances 0.000 description 7
- 235000020357 syrup Nutrition 0.000 description 7
- 229920002261 Corn starch Polymers 0.000 description 6
- 239000008120 corn starch Substances 0.000 description 6
- 229940099112 cornstarch Drugs 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229960002180 tetracycline Drugs 0.000 description 6
- 229930101283 tetracycline Natural products 0.000 description 6
- XIYOPDCBBDCGOE-IWVLMIASSA-N (4s,4ar,5s,5ar,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methylidene-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C=C1C2=CC=CC(O)=C2C(O)=C2[C@@H]1[C@H](O)[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O XIYOPDCBBDCGOE-IWVLMIASSA-N 0.000 description 5
- 229940042016 methacycline Drugs 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 229960001375 lactose Drugs 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000004100 Oxytetracycline Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229960000625 oxytetracycline Drugs 0.000 description 3
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 3
- 235000019366 oxytetracycline Nutrition 0.000 description 3
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 239000004099 Chlortetracycline Substances 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- -1 abbreviated CT C Chemical compound 0.000 description 2
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 2
- 229960004475 chlortetracycline Drugs 0.000 description 2
- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 2
- 235000019365 chlortetracycline Nutrition 0.000 description 2
- 229960002398 demeclocycline Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002906 microbiologic effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical group CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Chemical group 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 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
- 206010011891 Deafness neurosensory Diseases 0.000 description 1
- 206010014671 Endocarditis enterococcal Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Chemical group 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Chemical group 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Chemical group 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical group 0.000 description 1
- 229940071889 combination of tetracyclines Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical group O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229920000609 methyl cellulose Chemical group 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Chemical group 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical group 0.000 description 1
- 239000000196 tragacanth Chemical group 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/65—Tetracyclines
Definitions
- This invention relates to improved antibiotic compositions of the tetracycline type.
- antibiotic therapy has been very widespread. Normally a single antibiotic, chosen for its known effectiveness against a diognosed or suspected microorganism, has been used; and for most antibiotics recommended daily dosage has been determined. Proposals have been made to use different types of antibiotic in a combined dose. In a few cases, such as enterococcal endocarditis and some resistant strains of Staphylococcus, combinations of antibiotics of different types have proven effective. Also in some cases combinations of an antibacterial and an antifungal have been used. Many if not most of the proposed compositions have either been no more effective than a single antibioctic or in some cases there has been serious antogonism.
- the bacteriostatic antibiotics of which the tetracyclines with which the present invention deals are members, have either shown antogonism, for example in combinations of the tetracyclines and penicillin, or lack of useful improved results. It should be noted that the distinction between bactericidal and bacteriostatic antibiotics is one which is only of significance in tests made in vitro. When tests are made in living animals or men, all that can be determined is whether or not a drug shows good antibacterial activity. It cannot be determined Whether the test animals or man recovered because the antibiotic actually killed bacteria on contact with them, that is to say was bactericidal, or whether it was merely bacteriostatic and inhibited or very greatly reduced the rate at which the bacteria reproduced themselves.
- the present invention is directed to a combination of tetracyclines, all of them of course being bacteriostatic antibiotics which have been considered unsuitable for combination antibiotic therapy.
- the compositions of the present invention use three tetracyclines in doses which are much smaller for each tetracycline than those normally used with the tetracycline alone. Results are obtained which show as high antibacterial activity in the blood of patients to whom the tripleantibiotic has been given, but the side effects which are often very undesirable, such as nausea, gastrointestinal disturbances, and the like, are eliminated or drastically reduced over thoseof comparable doses of a single antibiotics. As a result, the problems of side effects with most patients are not significant with the preferred doses which will be set out below.
- tetracyclines which are preferred are a mixture of tetracycline itself, hereinafter abbreviated TC; chlortetracycline, abbreviated CT C, and demethylchlortetracycline, abbreviated DMCT.
- TC tetracycline
- CT C chlortetracycline
- DMCT demethylchlortetracycline
- the triple combinations may also include oxytetracycline in place of part or all of the TC, or methacycline in place of .part or all of the DMCT.
- Such combined antibiotic compositions are therefore included in the broader aspects of the present invention.
- the minimum single dose to produce a concentra tion sufficient to show effective antibacterial activity is about 50 mg. TC, 25 mg. CTC, and 25 mg. DMCT, or a total of about 100 mg. If oxytetracycline or methacycline replaces TC or DMCT, the same amounts apply, which will be true in the other dosage limits to follow.
- the maximum single dose is about 500 mg. TC, 250 mg. CTC, and 300 mg. DMCT.
- the preferred dosage for a day is about one third the daily dose of each antibiotic alone, i.e. 333 mg. TC, 333 mg. CTC, and 200 mg. DMCT, or a total of 866 mg.
- the maximum daily dosage under the present invention may be up to twice as great for each ingredient, with a total of 1732 mg. It should be noted that this maximum dose depends on the sensitivity of the organism and tolerance of the patient.
- compositions of the present invention produce antibacterial activities in blood serum at all times during twenty-four hours after administration in excess of a dose of TC equal to the total weight of the composition.
- the composition is, therefore, more efifective than the same amount of TC and gives considerably better antibacterial activities in blood serum over the total period.
- undesirable side effects such as nausea, gastrointestinal disturbances and the like, are either eliminated entirely or so drastically reduced that they do not involve any significant problems with most patients with the preferred daily doses.
- the improved antibacterial activities in the blood of patients as determined by antimicrobial microbiological assay are obtained not only Without offsetting side elfects but with a great reduction and, in the case of most patients, complete elimination of the side eifects which were encountered before. It is not desired to limit the present invention to any theory of the mechanism by which this desirable result is obtained. It is possible that the three tetracyclines have synergistic properties without any comparable eifect on side effects, but the invention is in no sense limited to this particular theory, which is advance as only one of a number of possible explanations. What is known is that improved antibacterial activities with greatly reduced or eliminated undesirable side effects are obtained as compared with the same total dose of each antibiotic when taken alone.
- a powdered mixture of the three tetracyclines with a suitable excipient may be filled into a gelatin capsule for oral use.
- Tablets may be made with a suitable binder such as acacia gum, cornstarch, gelatin and the like, with suitable disintegrating agents such as cornstarch, potato starch, alginic acid and the like, and the customary lubricant such as stearic acid, magnesium stearate, talc, etc.; or syrups or drops may be prepared with suitable sweetening agents, flavoring agents and the like.
- the tetracyclines need not be in the form of the free bases and, in fact, it is generally desirable to use the antibiotics in the form of the hydrochloride salt.
- the active ingredients and lactose are blended together thoroughly to form a homogeneous mixture.
- the powder is used to fill hard gelatin capsules of a suitable size at a gross filled weight of 360 milligrams. Each capsule then contains a total of 250 milligrams of antibiotics in the proportion of one part each of TC HCl and CTC HCl and 0.6 part of DMCT HCl.
- composition described above was tested clinically on twelve subjects, six of whom first received TC HCl in the quantity above, namely 250 mg, and six of whom received a capsule of the three antibiotics. Blood samples were taken at regular intervals during twenty-four hours and antibacterial activities were determined. One week later the subjects who were given the TC HCl were given a capsule of the three antibiotics and the subjects who were given a capsule of three antibiotics the first week were given a capsule of TC HCl. Antibacterial activity was determined by microbiological assay procedures using a standard test for tetracycline antibiotics as given by Grove and Randall (Grove, D. C., and Randall, W.
- the above syrup or pediatric drops has a pH of about 4.0-6.0.
- various agents can be used in place of those shown in the above formulation.
- suspending agents such as Vegum magma (complex colloidal magnesium-aluminum silicate) can be replaced with bentonite magma, tragacanth, carboxymethyl cellulose, methyl cellulose, carbopol 934 (carboxyvinyl polymer of high molecular weight), etc.
- the phosphates used as buffers in the above formulation can be replaced with citrates or tartrates.
- preservatives such as parabens others can be used such as alkali metal benzoates, sorbic acid, etc.
- the sugar and sorbital can be replaced as a whole or in part with corn syrup, glycerol, invert sugars, etc.
- the adjuvants, such as dyes and flavors can be replaced in whole or in part with sequesterene, bisulfites, etc.
- EXAMPLE 4 Oral syrup or drop preparation An oral preparation of syrup or pediatric drops may be formulated substantially as in Example 3 above, substituting the calcium salts of the tetracyclines in place of the neutral tetracyclines. The pH of the preparations should be adjusted to 8.0-9.0 by suitable bufier adjustments.
- Example 5 The procedure of Example 1 was repeated replacing the DMCT with an equal weight of methacycline. A product was produced which exhibited improved antibacterial activity in blood serum and decreased side effects.
- Example 6 The procedure of Example 2 was repeated replacing the DMCT with an equal weight of methacycline. Products were produced which showed improved antibacterial activity in blood serum and the same desirable lack of side effects.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46240765A | 1965-06-08 | 1965-06-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3454697A true US3454697A (en) | 1969-07-08 |
Family
ID=23836330
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US462407A Expired - Lifetime US3454697A (en) | 1965-06-08 | 1965-06-08 | Tetracycline antibiotic compositions for oral use |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US3454697A (enrdf_load_html_response) |
| BE (1) | BE682244A (enrdf_load_html_response) |
| BR (1) | BR6680268D0 (enrdf_load_html_response) |
| CY (1) | CY550A (enrdf_load_html_response) |
| ES (1) | ES327705A1 (enrdf_load_html_response) |
| FR (1) | FR5503M (enrdf_load_html_response) |
| GB (1) | GB1080617A (enrdf_load_html_response) |
| NL (1) | NL6607935A (enrdf_load_html_response) |
Cited By (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1984001895A1 (en) * | 1982-11-18 | 1984-05-24 | Univ Tufts | Tetracycline activity enhancement |
| US5064821A (en) * | 1982-11-18 | 1991-11-12 | Trustees Of Tufts College | Method and compositions for overcoming tetracycline resistance within living cells |
| WO1993008806A1 (en) * | 1991-11-06 | 1993-05-13 | Trustees Of Tufts College | Reducing tetracycline resistance in living cells |
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Also Published As
| Publication number | Publication date |
|---|---|
| GB1080617A (en) | 1967-08-23 |
| FR5503M (enrdf_load_html_response) | 1967-10-30 |
| BE682244A (enrdf_load_html_response) | 1966-12-08 |
| CY550A (en) | 1970-08-04 |
| NL6607935A (enrdf_load_html_response) | 1966-12-09 |
| ES327705A1 (es) | 1967-08-01 |
| BR6680268D0 (pt) | 1973-12-26 |
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