Effect of auxiliary substances on the bioavailability of tetracycline hydrochloride capsules (an in vitro study)

The rate of tetracycline hydrochloride transfer into solution from capsules containing different auxiliary substances was studied. It was shown that the dispersity level of tetracycline hydrochloride powder had no significant effect on the capsule disintegration and the rate of the antibiotic transfer into solution. The effect of the auxiliary substance composition on the capsule disintegration and the rate of the antibiotic dissolution was shown. The rate of tetracycline liberation from the capsules containing tetracycline hydrochloride without additives or the antibiotic in combination with 23 per cent of lactose was 4 to 6 times higher than that from the capsules with magnesium carbonate or calcium phosphate as the auxiliary substances.     

Therapeutic Agents in Acne Vulgaris: I. Tetracycline

A total of 120 consecutive patients with pustular and cystic acne vulgaris were selected for study. Patients were assigned a placebo and a tetracycline medication in a random method. Of the 53 patients who were given tetracycline, 45 showed some response, which was fair in 19 and excellent in 26. Of the 55 patients who received placebo, 24 showed no response while 31 showed some improvement. No side effects were reported. The difference in response between the two groups is statistically significant. It is concluded that administration of 250 mg. tetracycline four times daily, even for periods as short as two weeks, enhances the likelihood of improvement of cystic or pustular acne vulgaris.     

Tetracycline and benign intracranial hypertension: report of five cases.

Benign intracranial hypertension occurred in four young women taking tetracycline for acne; two were also taking vitamin A. In a fifth case a 14-year-old boy developed papilloedema after taking a short course of tetracycline for bronchitis. All symptoms disappeared soon after stopping the drugs, though in two cases the papilloedema persisted for many months. Benign intracranial hypertension should be sought in any young woman complaining of headache during treatment with tetracycline. Moreover, young women given vitamin A and tetracycline in combination for acne may be at special risk and should be kept under surveillance.     

盐酸四环素浓度和食物密度对萼花臂尾轮虫生活史特征的综合影响

近年来,抗生素的环境污染问题已引起人们的广泛关注,其在环境中的残留可对水生态系统的结构和功能产生重要影响。迄今,盐酸四环素浓度和食物密度对轮虫生活史特征的影响研究尚未见报道。以萼花臂尾轮虫(Brachionus calyciflorus)为受试动物,研究了在不同斜生栅藻(Scenedesmus obliquus)密度下,不同浓度的盐酸四环素(Tetracycline hydrochloride)对萼花臂尾轮虫生活史特征的影响。结果表明,食物密度和盐酸四环素浓度对轮虫的生命期望、净生殖率、世代时间、内禀增长率、平均寿命和后代混交率,以及食物密度和盐酸四环素浓度间交互作用对除了内禀增长率外的其他5个统计学参数均具有显著影响。在各食物密度下,轮虫的特定年龄繁殖率高峰值随着盐酸四环素浓度的增加呈现先增加后降低的趋势;盐酸四环素对轮虫生长和繁殖参数的影响呈现"低促高抑"的特点。3个食物密度下,高浓度的盐酸四环素显著提高了萼花臂尾轮虫的后代混交率,且在1.0×10~6个/mL藻密度下毒物浓度与轮虫后代混交率间具有显著的剂量-效应关系。食物密度的高低显著影响盐酸四环素对萼花臂尾轮虫的毒性效应。     

Molecular Complexes of Tetracycline Acid Salts

The different behavior of 5-hydroxytetracycline from tetracycline on the complex formation in spite of the similarity of both complexes in X-ray diffraction patterns, and the difficulty of complex formation of 7-chlorotetracycline, are suggestive of the hindrance effect of 5-hydroxy or 7-chioro group for the formation of complex lattice. Applying the above properties, tetracycline is separated from 5-hydroxytetracycline as the sulfate-succinimide complex, and tetracycline and 5-hydroxytetracycline are separated from 7-chlorotetracycline as their oxalic acid, sulfate-oxalic acid, sulfate-hydantoin and sulfate-succinimide complexes. 7-Chlorotetracycline is recovered as the hydrogenmaleate or the hydrochloride from the mother liquor.     

Acne: double blind clinical and laboratory trial of tetracycline,oestrogen-cyproterone acetate,and combined treatment.

Since the recent introduction of a drug regimen containing 2 mg of the antiandrogen cyproterone acetate and 50 micrograms ethinyl-oestradiol (Diane; oestrogen-cyproterone acetate) several uncontrolled reports have extolled the benefits of this drug. Double blind studies, however, are lacking. Sixty two patients with moderate or moderately severe acne were therefore included in a double blind trial of treatment for six months comparing tetracycline alone, oestrogen-cyproterone acetate alone, and a combination of these agents. Sebum excretion rates and bacterial counts were measured before, during, and after treatment, at the same time as a clinical assessment was made. At six months the acne (as assessed by overall grade) had improved by 68% in the antibiotic treated group and by 74% in the oestrogen-cyproterone treated group. The group given a combination of both agents improved by 82%, which was significantly better (p less than 0.025) than the improvement in the tetracycline treated patients. No significant difference was found between the groups given oestrogen-cyproterone alone and the combined treatment. The sebum excretion rate was suppressed by 25% in the patients in both groups receiving oestrogen-cyproterone but not in the group given antibiotics alone. Oestrogen-cyproterone acetate is as effective as antibiotics in treating acne in women, and adding antibiotics offers no advantage over using oestrogen-cyproterone on its own, although in this study the combination was more effective than tetracycline alone at six months.     

Therapeutic Agents in Acne Vulgaris: Part II. D-Alpha Amino Benzyl Penicillin,Erythromycin and Sulfadimethoxine

A total of 379 patients with pustular and cystic acne vulgaris were selected for study in three groups. Each group was assigned one of the following medications: benzyl penicillin, erythromycin, sulfadimethoxine, or placebo; these were to be compared with tetracycline, a medication whose effectiveness was previously demonstrated in this type of acne. The study revealed a larger number of favourable responses to tetracycline and erythromycin than to sulfadimethoxine. Sulfadimethoxine, however, produced a greater number of favourable responses than did the benzyl penicillin or the placebo; the last-named had equivalent results.     

Tetracycline hydrochloride complex formation with collagen

The quantitative indices and regularities of tetracycline hydrochloride binding with colelagen in the process of complex formation were studied in vitro. It was found that tetracycline-interacted with collagen. The amount of the antibiotic bound depended on its initial concentration in the mixture and the aggregate state of the protein: the amount of tetracycline hydrochloride absorbed by dissloved collagen was 10 times higher than that absorbed by polymerized collagen. The antibiotic bound with collagen did not lose its specific antibacterial activity.     

Recurrent oral ulceration treated with Mysteclin: a controlled study.

Twenty patients with recurrent oral ulceration participated in a placebo-controlled, double-blind trail of Mysteclin syrup (tetracycline hydrochloride and amphotericin) used as a mouthwash. Though a small, consistent improvement occurred with placebo, there was a significant reduction in mean pair scores and numbers of new ulcers recorded daily during the active-treatment periods, the effect lasting for at least four weeks after treatment was stopped. In contrast to topical steroid preparations, Mysteclin syrup is efficacious when begun at any stage of the disorder and is not associated with adverse systemic effects.     

Embryotoxicity and the immunodepressive action of tetracycline and its epi- and anhydro- derivatives]

The toxic effect of tetracycline and its epi- and anhydro-derivatives on growing chick embryos and the spleen cells of immunized mice was studied. High acute toxicity of 4-epianhydrotetracycline with respect to the chick embryos was found. Its LD50 was 4.8 times lower than toxicity of tetracycline hydrochloride. The characteristics of the acute toxicity was confirmed by the data on the embryo survival by the time of hatching. The same survival rate, i. e. 12 per cent was observed with the use of tetracycline and 4-epianhydrotetracycline in doses of 1000 and 100gamma per embryo respectively. Comparative investigation of the effect of tetracycline and anhydrotetracycline on the spleen cells revealed high toxicity of anhydrotetracycline which induced the same decrease in the number of the antibody-producing cells as tetracycline when used in doses 40 to 100 times lower than those of tetracycline. High toxicity of the anhydro-derivatives of tetracycline was also observed with respect to their teratogenic effect. Extremely pronounced anomalies in the embryo development were observed after exposure to 500gamma of 4-epianhydrotetracycline.     

Bioavailability of tetracycline hydrochloride capsules (an in vivo study)]

Blood absorption of tetracycline hydrochloride of various dispersity levels from capsules containing tetracycline alone or in combination with additives, such as magnesium carbonate and calcium salts was studied on humans. It was found that higher dispersity levels of tetracycline hydrochloride powder in capsules was not accompanied by increased blood absorption of the antibiotic. Addition of magnesium carbonate and calcium salts to the antibiotic in the process of capsulation markedly retarded the blood absorption. Clear correlation between the antibiotic dissolution rate in vitro and intensity of its blood absorption in volunteers was shown.     

Tetracycline-Cu(II) photo-induced fragmentation of serum albumin

The protein-damaging potential of photosensitized tetracycline hydrochloride alone and in combination with the metal ion Cu(II) was assessed using serum albumin as a model protein. Exposure of tetracycline to white light in an aqueous solution triggered the generation of significant amounts of reactive oxygen species (ROS) and engendered substantial protein damage. The appearance of distinct low-molecular-mass protein bands on 10% SDS-polyacrylamide gel ascertained the tetracycline concentration-dependent fragmentation of albumin. Photoexcited tetracycline in combination with 100 microM Cu(II) enhanced the protein fragmentation process with concurrent increase in free radical production. The significant release of acid-soluble amino groups and carbonyl groups from treated albumin provided quantitative estimation of protein fragmentation at 0-1.0 mM concentrations of tetracycline. Cu(II) ions per se did not cause any perceptible protein damage. The results with free radical quenchers suggested the role of hydroxyl radicals (*OH) in tetracycline-Cu(II)-induced protein fragmentation, as no superoxide dismutase (SOD)-mediated quenching effect was noted. The generation of free radicals upon tetracycline photoexcitation and consequent protein fragmentation may be considered as important factors in augmentation of tetracycline-induced phototoxic responses.     

Effect of vaccination therapy for acne,using a staphylococci antigenic complex in combination with clindamycin

A group of 46 patients with acne vulgaris were prescribed clindamycin in combination with a vaccination therapy using a staphylococci antigenic complex (Polystafana; Sevapharma, Czechia). Acne papulopustulosa was diagnosed in 36 patients and acne indurata in 10 patients. The clinical effect of clindamycin and Polystafana was determined on the basis of the regression of the inflammatory manifestation of acne: regression by 0-30% was considered unsuccessful, by 30-80% satisfactory, and above 80% excellent; the immunomodulation effect of the treatment was evaluated in parallel. The clinical effect was excellent in 21 patients with acne papulopustulosa and in 6 with acne indurata; it was accompanied by pronounced immunomodulation effect as both cellular and humoral immunity was also tended to return to normal values. A satisfactory clinical effect was observed in 15 patients with acne papulopustulosa, whose cellular immunity component was also stimulated. Only 4 patients with acne indurata failed to respond successfully. These were the patients who showed a pronounced deficit of the cellular immunity component persisting even after the treatment. The administration of clindamycin in combination with Polystafana vaccination can be recommended as an effective means for the treatment of acne vulgaris.     

Hepatoprotective effect of Tibetan remedy "Dig-Da-Shi-Tan"]

In experiments on albino rats with toxic hepatitis due to their exposure to tetracycline hydrochloride it was shown that a course of therapeutic and preventive administration of Dig-da-shi-tan decoction had a strong hepatoprotective effect. Antioxidative, membrane integrative, cholagogic and antiinflammatory activities of the remedy were revealed.     

Differentiation of the degree of bioavailability of peroral drug forms of tetracycline hydrochloride in experiments on laboratory animals]

Difference in the levels of bioavailability of 4 types of tetracycline hydrochloride tablets was shown on rabbits and guinea pigs. The rates of the antibiotic absorption into the blood of the laboratory animals and volunteers were the same. Relation between the rate of disintegration of various types of tablets of tetracycline hydrochloride and the antibiotic blood levels in the rabbits after administration of the same tablets was found.     

The release dynamics of salicylic acid and tetracycline hydrochloride from the psyllium and polyacrylamide based hydrogels (II)

Psyllium, a medicinally active natural polysaccharide, has been modified with polyacrylamide to develop the hydrogels; those can act as the potential candidate for novel drug delivery systems. In the present studies, the release dynamics of model drugs (salicylic acid and tetracycline hydrochloride) from the drug-loaded hydrogels have been discussed, for the evaluation of the drug release mechanism and diffusion coefficients. It has been observed that diffusion exponent ‘n’ have 0.68 and 0.74 values and gel characteristic constant ‘k’ have 1.625 × 10⁻² and 1.272 × 10⁻² values, respectively, for the release of salicylic acid and tetracycline hydrochloride in distilled water from the drug loaded hydrogels. Therefore, drug release from the drug loaded hydrogels through Non-Fickian or Anomalous diffusion mechanism where the rate of drug diffusion and rate of polymer relaxation were comparable. The effect of pH on the release pattern of tetracycline has been studied by varying the pH of the release medium. However, in each release medium, the Initial diffusion coefficient was observed to be more than the late time diffusion coefficient.     

Synthesis, characterization and swelling studies of pH responsive psyllium and methacrylamide based hydrogels for the use in colon specific drug delivery

In order to utilize the psyllium husk a medicinally important natural polysaccharide and to develop the novel hydrogels meant for the colon specific drug delivery, we have prepared psyllium and methacrylamide based polymeric networks by using N,N′-methylenebisacrylamide (NN-MBAAm) as crosslinker and ammonium persulfate (APS) as initiator. To study various structural aspects of the polymeric networks thus formed psy-cl-poly(MAAm), these were characterized with SEMs, FTIR, TGA and swelling studies. The swelling studies of networks were carried out as a function of time, temperature, pH and [NaCl]. Equilibrium swelling has been observed to depend on both composition of the polymer and nature of swelling medium. Maximum percent swelling 1262 was observed for the polymeric network prepared with 19.45 × 10⁻³ mol/L of [NN-MBAAm] at 40 °C in 0.5 M NaOH solution. This article also discusses the release dynamics of tetracycline hydrochloride from the hydrogels, for the evaluation of the drug release mechanism and diffusion coefficients of drug from the polymer matrix. The effect of pH on the release pattern of tetracycline hydrochloride has been studied by varying the pH of the release medium. It has been observed from the release dynamics of drug from the hydrogels that the diffusion exponent ‘n’ have 0.477, 0.423 and 0.427 values and gel characteristic constant ‘k’ have 5.07 × 10⁻², 6.34 × 10⁻² and 6.38 × 10⁻² values, respectively, in distilled water, pH 2.2 buffer and pH 7.4 buffer solution. The values the ‘n’ indicated that the Fickian type diffusion mechanism occurred for the release of tetracycline hydrochloride from drug loaded psy-cl-poly(MAAm) polymers in different release mediums. In Fickian type diffusion mechanism, the rate of polymer chain relaxation is more as compare to the rate of drug diffusion from these hydrogels and release behavior follows Fick’s law of diffusion. In each release medium, the values of the initial diffusion coefficient ‘D_i’ for the release of tetracycline hydrochloride was higher than the values of late time diffusion coefficient ‘D_L’ indicating that in the start, the diffusion of drug from the polymeric matrix was faster as compare to the latter stages.     

Action of Lincomycin on Staphylococci

On a solid medium, 0.1 to 1 μg/ml of lincomycin hydrochloride had a bacteriostatic effect upon 95 of 100 strains of staphylococci. Using cellophane transfers, we observed a bactericidal effect upon 54 of these strains after 3 to 14 hr of contact with 1 μg/ml. Five staphylococcal strains resistant to 100 μg/ml of lincomycin were also resistant to penicillin G, streptomycin, erythromycin, tetracycline, chloramphenicol (three strains), and rovamycin (three strains). Other staphylococcal strains resistant to methicillin, ampicillin, tetracycline, streptomycin, chloramphenicol, and erythromycin were sensitive to lincomycin.     

Antibiotic-resistant Propionibacterium acnes on the skin of patients with moderate to severe acne in Stockholm

The objective was to study the prevalence and antibiotic susceptibility patterns of Propionibacterium acnes strains isolated from patients with moderate to severe acne in Stockholm, Sweden and to determine the diversity of pulsed-field gel electrophoresis types among resistant P. acnes strains. One hundred antibiotic-treated patients and 30 non-antibiotic-treated patients with moderate to severe acne participated in the investigation. Facial, neck and trunk skin samples were taken with the agar gel technique. The susceptibility of P. acnes strains to tetracycline, erythromycin, clindamycin and trimethoprim-sulfamethoxazole was determined by the agar dilution method. The genomic profiles of the resistant strains were determined by pulsed-field gel electrophoresis. In the group of patients treated with antibiotics, resistant P. acnes strains were recovered in 37%, while in the non-antibiotic group of patients the incidence of resistant strains was 13%. Thus antibiotic-resistant P. acnes strains were significantly more often isolated from antibiotic-treated patients with moderate to severe acne than from non-antibiotic-treated patients (odds ratio, 3.8; P=0.01). There was a genetic diversity among the P. acnes strains. Forty-four different patterns of SpeI DNA digests were detected and two predominant clones were found. P. acnes strains exhibited different antibiotic susceptibility patterns and identical genotypes or vice versa. A person can be colonized with different strains with varying degrees of antibiotic resistance. The risk of increased resistance of P. acnes must be considered when treating acne patients with antibiotics, and especially long-term therapy should be avoided.     

A comparative study of raw garlic extract and tetracycline on caecal microflora and serum proteins of albino rats

Studies conducted on the comparative action of raw garlic extract and tetracycline hydrochloride on equal concentrations showed the raw garlic extract to be a more potent antimicrobial agent than tetracycline. The reversion to normalcy of caecal microflora and serum proteins after the withdrawal of test materials indicated an inverse relation between intestinal microflora and serum globulins.