With the development of natural products, the research activities on the solubilization methods of water-insoluble natural products have been carried out worldwide. Big molecular weight and poor solubility of most natural active ingredients lead to a very poor oral absorption and low bioavailability, which has extremely limited their development in pharmaceutical fields and clinical application. As a result, it is necessary to find out a suitable technique to improve the solubility and enhance the oral bioavailability of insoluble natural drugs. Based on the related references published in these years, this review introduced some new techniques to improve the solubility and bioavailability of natural drugs, including prodrugs, inclusion complex, solid dispersion, cocrystals, osmotic pump, liquisolid compacts, micronization, self-microemulsifying, nanosuspensions, lipsomes, polymeric micelles and so on, and summarized the theory, characteristics, application range, application examples, problems and development direction of each technique.
Administration, Oral ; Biological Availability ; Biological Products ; administration & dosage ; chemistry ; pharmacokinetics ; Chemistry, Pharmaceutical ; methods ; trends ; Solubility ; Technology, Pharmaceutical ; methods ; trends ; Water

MicroRNAs (miRNAs) are a set of non-coding small RNA molecules that play a critical role in regulation of protein coding genes in cells. MiRNAs have been extensively studied as novel biomarkers, therapeutic targets, and new drugs in various human diseases. Breast cancer is a one of the leading tumor types significantly affecting women health worldwide. Over the past decade, a number of natural agents, such as paclitaxel and curcumin, have been applied for treatment and prevention of breast cancer due to their relatively low toxicity. However, the mechanisms of action have not been completely understood. Investigation on miRNAs is able to potentially provide a novel insight into better understanding the anticancer activities of these natural products. Given that a single miRNA can target multiple genes, theoretically, those genes involved in a certain phenotype can be clustered with one or a few miRNAs. Therefore, pleiotropic activities of natural agents should be interpreted by interactions between selected miRNAs and their targets. In this review, we summarize the latest publications related to the alterations of miRNAs by two natural agents (paclitaxel and curcumin) that are currently used in intervention of breast cancer, and conclude that the mechanism involving the regulation of miRNA expression is one of the keys to understand pleiotropic activities of natural agents.
Animals ; Antineoplastic Agents ; administration & dosage ; Biological Products ; administration & dosage ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; prevention & control ; Curcumin ; administration & dosage ; Female ; Humans ; MicroRNAs ; genetics ; metabolism ; Paclitaxel ; administration & dosage

With related global patent data as analysis samples, worldwide patent overview of Ginkgo biloba preparation is analyzed in application, applicant, technical distribution and so on. This research shows that the most important areas of G. biloba preparation are Europe and China. The European applicants start earliest along with developing smoothly, moreover, their patents have best quality. The Chinese applicants start late along with the fastest growing, and have already certain research capabilities, moreover, their patents' quality needs to be improved. This research result provides reference for development of G. biloba preparation. The author suggest that Chinese applicants learn techniques and layout experiences of other's patents fully to enhance the level of new drug development and patent protection.
Biological Products ; Chemistry, Pharmaceutical ; legislation & jurisprudence ; manpower ; methods ; organization & administration ; China ; Europe ; Ginkgo biloba ; chemistry ; Humans ; Patents as Topic ; legislation & jurisprudence

Multidrug resistance (MDR) in human cancer is one of greatest challenges in cancer therapy. Natural products, especially the alkaloids, exert reversed effects on MDR with low toxicity, by interacting with various targets. In this review article, we summarize the recent progress made in the research of the main alkaloids, including classification, function, mechanism, research status, and application in reversing MDR.
Alkaloids ; administration & dosage ; chemistry ; Animals ; Biological Products ; administration & dosage ; chemistry ; Drug Antagonism ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Neoplasms ; drug therapy

Gastrodia elata Blume is a well-known kind of natural products used as a folk medicine for thousands of years. However, anti-atopic dermatitis-like effects of G. elata Blume had not been evaluated until now. The aim of the present study is to investigate the protective effects of water extract from the roots of G. elata Blume (GE) on 2, 4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions using balb/c mice. Combination treatment of GE (at a dose of 12.5 mg/kg body weight by administrated per os + 0.5 mg/cm2 as ointment to apply on ear and dorsal skin) was significantly inhibited spleen weight, ear thickness, levels of serum immunoglobulin E and number of mast cells, compared with that of 2, 4-dinitrochlorobenzene-included groups without GE. Furthermore, combination application by oral administration plus by ointment of GE significantly inhibited the histamine release from rat peritoneal mast cells. These results suggest that combination treatment of oral administration plus ointment form of GE could be helpful as a potentially natural pharmaceutical treatment on atopic-like dermatitis.
Administration, Oral ; Animals ; Biological Products ; Body Weight ; Dermatitis ; Dermatitis, Atopic ; Ear ; Gastrodia* ; Histamine Release ; Immunoglobulin E ; Immunoglobulins ; Mast Cells ; Medicine, Traditional ; Mice* ; Rats* ; Skin* ; Spleen ; Water

OBJECTIVE: To evaluate the clinical efficacy on the treatment of the low-middle frequency sudden hearing loss with postaurical injection of methylprednisolone. METHOD: The 80 cases of the low-middle frequency sudden hearing loss were randomly divided into postaurical injection and oral hormone groups. The postaurical injection group (42 cases) received the postaurical injection of methylprednisolone, 40 mg/2 d, combined with the treatment of Ginkgo dipyidamolum and Alprostadil for 14 d; The oral hormone group (38 cases) received the oral prednisone, 1 mg/kg/d, administrated once on the morning for 3 d, if effective, prolonging for another 2 d, as mentioned above for Ginkgo dipyidamolum and Alprostadil. RESULT: The total effective rate was 88.10% in postaurical injection group and 86. 4o%in oral hormone group. There was no significant difference between the twbogroups( P> 0. 5). CONCLUSION Postaurical injection of methylprednisolone for the low-middle frequency sudden hearing loss is effective, safe and simple, which may be an alternative for systemic administration of gulcocorticoid.
Alprostadil ; therapeutic use ; Biological Products ; therapeutic use ; Glucocorticoids ; administration & dosage ; therapeutic use ; Hearing Loss, Sensorineural ; Hearing Loss, Sudden ; drug therapy ; Humans ; Injections ; Methylprednisolone ; administration & dosage ; therapeutic use ; Prednisone ; administration & dosage ; therapeutic use ; Treatment Outcome

OBJECTIVETo observe the clinical efficacy and safety of Corydalis composite (CDC) combined with methotrexate (MTX) in treating rheumatoid arthritis (RA).

METHODSSeventy-six RA patients were randomly assigned to 2 groups, 37 in the treated group received the combined therapy, and the 39 received MTX treatment alone, all were treated for 12 weeks. Efficacy of treatment was evaluated adopting the standard of American College of Rheumatology (ACR), taking ACR20 as the chief criterion; ACR50, ACR70 as well as the clinical indexes and items in Health Account Questionnaire (HAQ) as the auxiliary criteria, including joint swelling index, joint tenderness index, holding power, morning stiffness time, resting pain, erythrocyte sedimentation rate (ESR), C-reactive protein. And the adverse reaction was recorded at the same time.

RESULTSAfter being treated for 4, 8 and 12 weeks, the ACR20 response rate reached 35.14%, 59.46% and 70.27% respectively in patients of the treated group, while that in the control group was 17.95%, 35.90% and 46.15% respectively, significant difference between groups was shown in the outcome of week 8 and 12 (P < 0.05). ACR50 and ACR70 improving rate at all the time points of observation were increased in the treated group, with the ACR50 improving rate at week 12 higher than that in the control group (43.24% vs. 20.51%, P < 0.05). As compared with the control group, the improvements in all the auxiliary criteria were more significant in the treated group (P < 0.05). The incidence of adverse reaction was less in the treated group than in the control group (32.43% vs. 56.41%, P < 0.05), particularly in term of the damage on liver (0 vs. 10.26%, P < 0.05).

CONCLUSIONCDC combined with MTX is more effective than MTX alone in treating active RA with less adverse reaction.

Adult ; Antirheumatic Agents ; administration & dosage ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Biological Products ; therapeutic use ; Corydalis ; Drug Therapy, Combination ; Female ; Humans ; Male ; Methotrexate ; administration & dosage ; therapeutic use ; Middle Aged ; Treatment Outcome

OBJECTIVEThe aim of this review is to objectively access the trial evidence on the role of omega-3, red yeast rice and garlic in preventing clinical cardiovascular events. Given the large number of clinical trials favoring statin use in cardiovascular disease, it is important to see if evidence is available for these supplements and whether they could replace statin therapy.

DATA SOURCEA PubMed search was conducted using the keywords 'trial, omega-3, red yeast rice, xuezhikang, garlic, cholesterol, cardiovascular, outcomes'; the resulting trials were reviewed together with the references quoted in the papers obtained.

STUDY SELECTIONThe studies selected are prospective, randomized, placebo-controlled studies with predefined clinical cardiovascular end-points recruiting at least 2000 patients, with a follow-up over 2 years.

RESULTSModest dose omega-3 fatty acid has been shown in GISSI-P (11 324 patients, follow-up 3.5 years) to produce a reduction in sudden death of 45%, and in cardiac death of 35%, acting probably via an anti-arrhythmic effect. In JELIS (18 645 patients, follow-up 4.6 years), high dose omega-3 given to Japanese patients on a high fish diet and already on statin treatment produced further benefit with a 19% reduction of nonfatal cardiovascular outcomes; fatal cardiac events are not affected. CCSPS (4870 patients, follow-up 4 years), a secondary prevention trial using xuezhikang, a commercial red yeast rice preparation, produced a 46% reduction in nonfatal myocardial infarction and coronary death. There has been no trial to show that garlic reduces clinical cardiovascular outcomes. A rigorous trial with constant assessment of chemicals in the study material in 192 patients found that over a 6-month follow-up, raw garlic and 2 commercial preparations do not significantly affect lipid levels.

CONCLUSIONSOmega-3 in modest doses reduces cardiac deaths, and in high doses reduces nonfatal cardiovascular events. Red yeast rice reduces adverse cardiac events to a similar degree as the statins. It is unlikely that garlic is useful in preventing cardiovascular disease.

Biological Products ; administration & dosage ; Cardiovascular Diseases ; prevention & control ; Fatty Acids, Omega-3 ; administration & dosage ; Garlic ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Phytotherapy ; Prospective Studies ; Randomized Controlled Trials as Topic

OBJECTIVETo observe the effects of compound red yeast rice extract (CRYRE) on blood lipids, hemorheology and blood coagulant system in rats with hyperlipidemia.

METHODSD rats were randomly divided into six groups: normal control group, model group, Xuezhikang group (0. 24 g x kg(-1)), CRYRE high dose group (2.4 g x kg(-1)), middle dose group (1.2 g x kg(-1)) and low dose group (0.6 g x kg(-1)). The normal control rats were given pure water, and rats of other five groups were given 10 mL kg lipid emulsion and subjected to daily intragastric administration simultaneously in two days, continuously for 3 weeks. After the last medication, all the rats were sacrificed for measurement of blood lipids, hemorheology and coagulation factors.

RESULTCRYRE 2.4 g x kg(-1) could significantly reduce the serum TG, TC levels and increase the HDL-C level (P < 0.01, P < 0.05). CRYRE 0.6-2.4 g x kg(-1) could significantly increase the ratios of HDL-C/TG,HDL-C/TC and HDL-C/LDL-C (P < 0.01). CRYRE 2.4 g x kg(-1) also reduced whole blood viscosity and plasma viscosity (P < 0.01, P < 0.05), prolonged active partial thromboplastin time, and lowered fibrinogen content (P < 0.01, P < 0.05).

CONCLUSIONCRYRE 2.4 g x kg(-1) could reduce blood lipids, blood viscosity and fibrinogen content, improve blood circulation, and depress the alteration of blood coagulant system resulted from lipid metabolic disorder in rats with hyperlipidemia.

Animals ; Biological Products ; administration & dosage ; chemistry ; Blood Circulation ; drug effects ; Disease Models, Animal ; Humans ; Hyperlipidemias ; blood ; drug therapy ; physiopathology ; Hypolipidemic Agents ; administration & dosage ; chemistry ; Lipids ; blood ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the effect of Group A streptococcus preparation (sapylin) combined with cisplatin on the malignant peritoneal effusion in patients with advanced cancer.

METHODSSixty advanced cancer patients with large amount of peritoneal effusion were divided into two groups: sapylin + cisplatin (DDP) group (30 patients) and control group (DDP alone, 30 cases). All the chemotherapeutic agents were injected intraperitoneally through a catheter.

RESULTSIn sapylin + cisplatin(DDP) group, 11 (36.7%) patients showed CR and 16 (53.3%) PR. The overall response rate (CR + PR) was 90.0%. Those of DDP alone group were 16.7% and 46.7%, the overall response rate was 63.3%. The main adverse effects were fever, nausea, and vomiting.

CONCLUSIONCombined Group A streptococcus preparation (sapylin) and cisplatin is more effective than cisplatin alone for the malignant peritoneal effusion in patients with advanced cancer, and the adverse effects are tolerable.

Adjuvants, Immunologic ; administration & dosage ; Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Ascitic Fluid ; pathology ; Bacterial Proteins ; administration & dosage ; Biological Products ; administration & dosage ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Female ; Humans ; Immunologic Factors ; administration & dosage ; Injections, Intraperitoneal ; Male ; Middle Aged ; Ovarian Neoplasms ; pathology ; therapy ; Peritoneal Neoplasms ; secondary ; therapy ; Stomach Neoplasms ; pathology ; therapy ; Streptococcus pyogenes ; chemistry