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PubMed2003

CPH 82.

CPH 82 [Reumacon] is a purified semi-synthetic lignan glycoside derivative of the medicinal herb Podophyllum emodi which inhibits microtubules. It has been jointly developed by the Swedish company Conpharm and the Swiss company Analytecon SA. It has potential for the treatment of rheumatoid arthritis. The Swedish company Meda is licencing the drug and has taken over responsibility from Conpharm for development and documentation. Meda has obtained exclusive marketing rights for Reumacon worldwide, except in China and some other Asian countries. Meda plans to form partnerships with other companies in the marketing of Reumacon.

Administration, Oral↗
PubMed2001

Aryltetralin lignans: chemistry, pharmacology and biotransformations.

Podophyllotoxin derivatives like etoposide 7a, etophos 7b, and teniposide 7c are used clinically as potent chemotherapeutic agents for a variety of tumors including small cell lung carcinoma, testicular cancer, and malignant lymphoma. These compounds derived from a series of modifications which converted podophyllotoxin 1a from an entity that interacted with tubulin and blocks mitosis to one that induced a block in late S or early G2 by interacting with topoisomerase II. Synthetic studies on podophyllotoxin derivatives can be divided in four general approaches (the oxo-ester route, the digydroxy acid route, the tandem conjugate addition route and the Diels-Alder route). Albeit a number of synthetic sequences afforded products with excellent enantiopurities, the low overall yields still disqualify synthesis as an alternative for naturally produced materials. An alternative route based on the enzyme-catalyzed cyclization of synthetic intermediates to analogues of the podophyllotoxin family is being explored. Synthetic dibenzylbutanolides, which were revealed by biosynthetic studies to be the precursors of aryltetralin lignans, have been treated with enzymes derived from cell cultures of Podophyllum peltatum, Catharanthus roseus, Nicotiana sylvestris and Cassia didymobotrya. The ciclyzation process afforded however compounds with a different stereochemistry in the C ring. The obtainment of a novel compound with a bynzylidenebenzylbutirolactone structure still leaves considerable scope for exploring biotransformations in order to obtain podophyllotoxin analogues via a combination of synthetic chemistry and biotechnological methods.

Animals↗
PubMed2000

Therapeutic applications of medicinal plants in the treatment of breast cancer: a review of their pharmacology, efficacy and tolerability.

Various active compounds (or their semi-synthetic derivatives) derived from medicinal plants have been assessed for their efficacy and tolerability in the treatment of breast cancer. Some of these plant species, including Taxus baccata (paclitaxel, docetaxel), Podophyllum peltatum (etoposide), Camptotheca acuminata (camptothecin) and Vinca rosea (vinblastine, vinorelbine) have well recognized antitumour activity in breast cancer, and have been evaluated in clinical trials. For example, results from recent Phase II/III trials have established docetaxel as the most active single agent in the treatment (first or second-line) of advanced metastatic breast cancer. For other plant species such as Panax ginseng and Allium sativum, antitumour activity has been evaluated in experimental studies using cultured cells and animal models, but the therapeutic potential in patients remains to be determined. Antitumour activity derived from medicinal plants may produce results via a number of mechanisms, including effects on cytoskeletal proteins which play a key role in mitosis (paclitaxel), inhibition of activity of topoisomerase enzymes I (camptothecin) or II (etoposide), stimulation of the immune system (Viscum album), or antiprotease-antioxidant activity. Medicinal plant-derived antineoplastic agents may be used in single agent or in combinational therapies, and have been used in first-line or second-line (including anthracycline-refractory patients) treatment of localized or metastatic breast cancer. Adverse effects resulting from the use of these agents include neutropenia and peripheral neuropathies.

Animals↗
PubMed2001

Direct medical costs for surgical and medical treatment of condylomata acuminata.

OBJECTIVE: To determine which treatment modalities for condylomata acuminata are associated with the lowest direct medical costs. DESIGN: Cost-effectiveness analysis. SETTING: Ambulatory private practice, primary or specialty care. PATIENTS OR OTHER PARTICIPANTS: Adults with no presenting complaints other than condylomata acuminata. INTERVENTIONS: Construction of a cost-effectiveness model. From a literature review, extraction of commonly accepted guidelines regarding duration and frequency as well as reports of efficacies of typical treatment regimens; from Medicare physician fee schedules, costs of physician visits and physician-administered treatments; from published data, average wholesale prices of medications. MAIN OUTCOME MEASURE: Estimated direct medical costs per complete clearance associated with different treatment options for condylomata acuminata. RESULTS: Mean direct medical costs per complete clearance are lowest for surgical excision ($285). Other low-cost modalities are loop electrosurgical excision procedure ($316), electrodesiccation ($347), carbon dioxide laser ($416), podofilox ($424), and pulsed-dye laser ($479). Higher-cost modalities are cryotherapy ($951), trichloroacetic acid ($986), imiquimod ($1255), podophyllum resin ($1632), and interferon alfa-2b ($6665). CONCLUSION: Surgical modalities, including excision, electrodesiccation, loop electrosurgical excision procedure, and laser, as well as podofilox are low-cost options for the treatment of condylomata acuminata.

Condylomata Acuminata↗
PubMedDate not supplied

[Neurological syndromes linked with the intake of plants and fungi containing a toxic component (I). Neurotoxic syndromes caused by the ingestion of plants, seeds and fruits].

INTRODUCTION: A wide range of plants, seeds and fruits used for nutritional and medicinal purposes can give rise to neurotoxic symptoms. DEVELOPMENT: We review the neurological pathology associated with the acute or chronic consumption of plants, seeds and fruits in human beings and in animals. Of the plants that can trigger acute neurotoxic syndromes in humans, some of the most notable include Mandragora officinalis, Datura stramonium, Conium maculatum (hemlock), Coriaria myrtifolia (redoul), Ricinus communis, Gloriosa superba, Catharanthus roseus, Karwinskia humboldtiana and Podophyllum pelatum. We also survey different neurological syndromes linked with the ingestion of vegetable foodstuffs that are rich in cyanogenic glycosides, Jamaican vomiting sickness caused by Blighia sapida, Parkinson dementia ALS of Guam island and exposition to Cycas circinalis, Guadeloupean parkinsonism and exposition to Annonaceae, konzo caused by ingestion of wild manioc and neurolathyrism from ingestion of Lathyrus sativus, the last two being models of motor neurone disease. Locoism is a chronic disease that develops in livestock feeding on plants belonging to Astragalus and Oxytropis sp., Sida carpinifolia and Ipomea carnea, which are rich in swainsonine, a toxin that inhibits the enzyme alpha mannosidase and induces a cerebellar syndrome. CONCLUSIONS: The ingestion of neurotoxic seeds, fruits and plants included in the diet and acute poisoning by certain plants can give rise to different neurological syndromes, some of which are irreversible.

Administration, Oral↗
PubMed2003

Er:YAG laser followed by topical podophyllotoxin for hard-to-treat palmoplantar warts.

BACKGROUND AND OBJECTIVES: Palmoplantar warts are often hard to treat. They tend to relapse and the course of therapy is frustrating in many cases. The erbium:YAG laser(Er:YAG) with a wavelength of 2.94 rm is capable of achieving a rapid and precise ablation of warts, but about 14% of patients are non-responders as shown in a previous study. Podophyllotoxin is an established antimitotic agent derived from podophyllum plant resin, approved for human papilloma virus (HPV)-induced genital warts. The combination of both ablative Er:YAG laser and topical 0.5% podophyllotoxin solution in hard-to-treat palmoplantar HPV warts was investigated. PATIENTS AND METHODS: Thirty-five patients with hard-to-treat warts(palmar or plantar) with a mean age of (32.2+12.1) years, range 17-50 years, with various pretreatments that had failed, were treated once by Er:YAG laser ablation with a spot size of 3 mm, a frequency between 8 Hz and 10 Hz, and a fluence of 5.7-11.3 J/cm2. After wound healing, topical podophyllotoxin 0.5% solution was applied for 3 days followed by a break of 4 days. Four to six treatment cycles with podophyllotoxin were performed. RESULTS: After laser treatment followed by topical podophyllotoxin cream a complete response was observed in 31 patients (88.6%). Two patients with plantar warts and a complete response showed a relapse within 3 months after treatment (5.7%). None of the patients developed pigmentary changes,wound infections or scarring. CONCLUSION: The therapy of hard-to-treat warts with a combination of Er:YAG laser and topical podophyllotoxin is safe and effective. Compared with laser alone, the CR percentage seems to be higher and the percentage of relapses reduced.

Administration, Topical↗
PubMed1992

[Studies on the TLC scanning determination of lignans in Diphylleia sinensis Li].

A simple, sensitive and accurate method for the separation and determination of the lignans: podophylltoxone (I), isopicropodophyllone (II), picropodophyllone (III), dehydropodophyllotoxin (IV), picropodophyllin (V), podophyllotoxin (VI), 4'-demethylpodophyllotoxin (VII) and diphyllin (VIII) is described. The sample solution was applied at a point 1 cm from the bottom edge of the HPTLC silica gel plate (10 cm x 10 cm), dichloromethane-diethyl ether (4:1) was used as the developing solvent. The plate was saturated for 30 min and then developed twice for 9.5 cm using ascending technique. The plate was sprayed with 2.5% ammonium ceric sulphate--20% nitric acid and toasted for 15 min at 120 degrees C, then fumigated with ammonia solution for 20 min at room temperature to intensify the spot color. The spots were scanned with a Shimadzu CS-930 TLC scanner. The contents of eight lignans in Diphylleia sinensis was calculated by comparison with standards spotted on the same plate. The standard curves were linear in the range of 0.48-2.52 micrograms for the eight lignans. The method has been applied to the analysis of various samples and can be used for the quality control of Diphylleia sinensis, podophyllum and dysosma preparations used in clinic.

Chromatography, Thin Layer↗
PubMed1992

Experimental podophyllotoxin (bajiaolian) poisoning: II. Effects on the liver, intestine, kidney, pancreas and testis.

Young male rats were orally intubated with podophyllotoxin: Group I, control animals, orally fed with vehicle only; Group II, fed with an initial dose of 5 mg.kg-1 b.w., followed by a daily dose of 1.67 mg.kg-1 b.w. for 7d. Group III, fed with an initial dose of 15 mg.kg-1 b.w., followed by a daily dose of 5 mg.kg-1 b.w. for 7d. All animals were sacrificed 72 h after the last dosing. Histopathological examination revealed dose-related fatty change of the liver, atrophy and degenerative changes of the intestinal epithelial linings and testicular seminiferous tubules. Depletion of the pancreatic acinar cell granules was also apparent in the Group III animals. No pathology, however, was observed in the kidneys. The present study demonstrated for the first time degenerative changes in the liver, intestine, testis, and pancreas of animals ingested podophyllotoxin. These pathological changes correlate well with the clinical signs/symptoms of abnormal liver function, abdominal pain and diarrhea, and reduced serum amylase in humans poisoned by podophyllum. Inhibition of protein synthesis and mitosis (disruption of microtubules) are believed to be the underlying mechanisms of these changes observed in the animals intoxicated by podophyllotoxin.

Animals↗
PubMed1990

Current status of podophyllotoxin for the treatment of genital warts.

An evolutionary process that began 50 years ago with a crude plant resin (podophyllum) has currently developed to the point where a fine chemical podophyllotoxin can be safely and effectively applied by patients for the treatment of external genital warts. In this brief review, the fundamental chemistry, pharmacology, and toxicology of podophyllotoxin will be reviewed, along with the sequence of clinical studies that resulted in the development of patient applied podophyllotoxin.

Condylomata Acuminata↗
PubMedDate not supplied

Inhibition of ConA-induced proliferative response in human lymphocytes by podophyllotoxin and a detergent, Tween80.

Podophyllotoxin (CPH86), at concentrations of 5 ng/ml or more, inhibited [3H]-thymidine uptake of ConA-induced proliferation of human peripheral mononuclear blood cells. Tween80, the detergent included in the anti-inflammatory drug Proresid, containing podophyllum lignan derivatives, also inhibited lymphocyte proliferation in a dose-dependent manner. Combination of the two drugs did not, or did only weakly, potentiate the inhibitory effect of each drug.

Concanavalin A↗
PubMed1980

Perianal apocrine gland adenoma.

A 59-year-old man had a pedunculate perianal tumor initially thought to be a condyloma acuminatum. Since it failed to respond to topical podophyllum resin, the growth was excised and found to be an apocrine gland tumor. Histological features included a duct extending from the surface epidermis to multiple tubules, which led to cystic spaces with papillary projections of columnar epithelium. Decapitation secretion and fibrous stromal proliferation were prominent. The clinical and histological similarities to other apocrine gland adenomas are briefly presented.

Adenoma↗
PubMed1995

Synthesis of podophyllotoxin congeners as potential DNA topoisomerase II inhibitors.

We have synthesized a number of new podophyllotoxin congeners in which the A-ring is opened and the C-ring is aromatic. These are based on the chemically modified structures of the naturally occurring podophyllum lignan, diphyllin. These have been synthesized by employing the Michael Initiated Ring Closure methodology. These lignans exhibited considerable DNA topoisomerase II inhibition and were devoid of topoisomerase I inhibition; they did not exhibit very significant activities in the in vitro human tumour cell lines assay. The results obtained provide insights into the structure-activity relationships and the design of chemically modified podophyllotoxin congeners useful in cancer chemotherapy.

Animals↗
PubMed1995

Noncervical human papillomavirus genital infections.

The incidence of human papillomavirus infection is increasing. More than 60 types of human papillomavirus have been isolated; some types are known to have malignant potential. Differential diagnosis of the lesions includes condyloma latum, seborrheic keratoses, nevi, pearly penile papules and neoplasms. The goal in treating noncervical human papillomavirus infection is the elimination of lesions; eradication of the virus is not yet possible. Current forms of treatment include cryotherapy, podophyllum resin, podophilox, trichloroacetic acid, laser ablation, loop electrosurgical excision procedure (LEEP), fluorouracil and alpha interferon. Success in treating condyloma may be increased if the area is first soaked with 5 percent acetic acid to more clearly show the extent of the local infection. Recurrence is a problem no matter what form of therapy is used.

Condylomata Acuminata↗
PubMed1994

Herbal poisoning caused by adulterants or erroneous substitutes.

Six cases of herbal poisoning involving six patients in Hong Kong, Taipei and Kuala Lumpur are reported. The sources of poisoning were identified as adulterants (Podophyllum emodi) or erroneous substitutes (Datura metel). In cases of suspected herbal poisoning, it is recommended that the prescriptions, herbal residues and herb samples should be collected for pharmacognostical and chemical analysis to substantiate the cause of poisoning. Insofar as it is possible, an estimate of the amount of herbs consumed should also be obtained, to establish whether the amount of toxin present is sufficient to account for the symptoms.

Drug Contamination↗
PubMed1994

[Herbalogical study of Chinese drug guijiu and xiaoyelian].

Through a critical study of ancient Chinese herbals, it is concluded that the botanical origin of Guijiu should be Dysosma versipellis or D. pleiantha instead of Sinopodophyllum emodi, and that Xiaoyelian was originated from the latter. In Chinese Pharmacopoeia and many other books, the botanical origin of Xiaoyelian was erroneously referred to as Podophyllum emodi.

China↗
PubMedDate not supplied

Antiproliferative effects on human peripheral blood mononuclear cells and inhibition of in vitro immunoglobulin synthesis by Podophyllotoxin (CPH86) and by semisynthetic lignan glycosides (CPH82).

A mixture of natural and semisynthetic (modified) glycosides from Podophyllum emodi (Proresid) has been used for many years in the treatment of rheumatoid arthritis, but its use is hampered by gastrointestinal side effects. Highly purified podophyllotoxin (CPH86) and a preparation containing two semisynthetic podophyllotoxin glycosides (CPH82) are currently being tested in clinical trials. In this study these drugs were shown to inhibit in vitro [3H]-thymidine uptake of human peripheral blood mononuclear cells stimulated by the mitogens concanavalin A, phytohemagglutinin and pokeweed mitogen. Complete inhibition was observed with CPH86 in concentrations > or = 20 ng/ml and with CPH82 in concentrations > or = 1 microgram/ml. In vitro production of IgG, IgM and IgA by PWM-stimulated cells cultured for 7 days was unaffected by 10 ng/ml CPH86 and 100 ng/ml CPH82, but was strongly inhibited by concentrations of CPH86 at > or = 20 ng/ml and CPH82 at > or = 1 microgram/ml. In conclusion, both CPH86 and CPH82 inhibit mitogen induced lymphocyte proliferation and immunoglobulin synthesis and the results may be of help in determining optimal dose levels if related to treatment effects.

Cell Division↗
PubMed1996

Human papillomavirus infection: treatment options for warts.

Human papillomavirus can produce verrucae, or warts, on cutaneous and mucosal surfaces. Although the diagnosis is usually straightforward, issues regarding the need for treatment and the choice of treatment are complex. The rationale for the treatment of viral warts is based on the prevention of spread to other areas of the body or to other people; the prevention of irritation, bleeding and other unwanted local effects of the wart; cosmetic and psychosocial considerations, and the possible association with neoplasia. A significant proportion of warts resolve spontaneously within two years. Many treatment options appropriate to primary care are available, including local application of salicylic acid, cantharidin, liquid nitrogen and podophyllum. Direct injection of interferon is a choice in selected cases. The decision to treat and the choice of modality must be individualized.

Humans↗
PubMed1996

Etoposide phosphate: what, why, where, and how?

The podophyllotoxin derivatives etoposide and teniposide are active in the treatment of a variety of malignant conditions. Both represent chemical modifications of podophyllin, an extract of Podophyllum peltatum (May apple, mandrake, Indian apple, wild lemon, or duck's foot), a plant long used as a folk remedy and recognized in the 19th century to be effective in the treatment of cancer. While etoposide is active in the treatment of many cancers and is widely used, it has a number of limitations due to its lack of water solubility. Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble prodrug of etoposide that is rapidly and completely converted to the parent compound after intravenous dosing. The pharmacokinetic profile of etoposide after treatment with either etoposide or etoposide phosphate is identical. Toxicity and clinical activity also are the same. Because etoposide phosphate is water soluble and can be made up to a concentration of 20 mg/mL, however, it can be given as a 5-minute bolus, in high doses in small volumes, and as a continuous infusion. Furthermore, it is not formulated with polyethylene glycol, polysorbate 80 (Tween; ICI Americas, Wilmington, DE), and ethanol, and does not cause acidosis when given at high doses. The easier-to-use etoposide phosphate represents an improved formulation of etoposide.

Antineoplastic Agents↗