Preliminary Studies On The Preparation And Pharmacokinetics Of The Supplemented Lindera Cataplasm

ObjectiveTo investigate the extraction process of volatile oil and alkaloids of the supplemented Lindera, provide the basis for the development and utilization of compound. Through prescription screening and process optimization, preparation of the supplemented Lindera cataplasm and established the quality standard to lay a solid foundation for the actual production;Preliminary studies on pharmacokinetics of the Supplemented Lindera cataplasm, provide guidance for the clinical application of its products.Methods and results1. Study on extraction process of medicinal herbs in the supplemented Lindera(1) Extraction of volatile oilBased on the pre-test and reference basis, with the total volatile oil as the index, design of single factor carries on the inspection to the solvent dosage, extraction time, soaking time and other factors, then to optimize the best extraction process by orthogonal design. The results show that, Rhizoma Cyperi, Radix Linderae, costus and Amomum villosum crushed into coarse grain, by steam distillation with water eight times after half hour immersion then extraction of four hours.(2) Study on extraction process of alcoholResidue of Rhizoma Cyperi, Radix Linderae, Costus and Amomum villosum after extracting volatile oil, Rhizoma Corydalis and Radix Glycyrrhizae with ethanol extraction, the extraction of tetrahydropalmatine content as index, design of single factor carries on the inspection to the solvent dosage, extraction time, ethanol concentration and other factors, then to optimize the best extraction process by orthogonal design. The results showed that Rhizoma Corydalis, Radix Glycyrrhizae were crushed into coarse powder, Residue of Rhizoma Cyperi, Radix Linderae, Costus and Amomum villosum after extracting volatile oil and Rhizoma Corydalis, Radix Glycyrrhizae with four times amount of60%alcohol and extracting for three times, each extraction forty-five minutes.2. Study on forming process of the supplemented Lindera cataplasm(1) Optimization of preparation and forming process of the blank matrixAccording to the appearance, adhesion, residual film, uniformity, spread, follow the impact as index,design of single factor carries on the inspection to adhesion agent, cataplasm preparation, cataplasm pH value, temperature and mixing process;the water loss rate as index to optimize the moisturizing agent and its amount;the recovery rate and deformation rate as the index selection of crosslinking agent;then with adhesive, moisturizing agent, amount of crosslinking agent to arrange the uniform experimental design factors, to optimum the best ratio of matrix.Results show that, The best prescription is the extraction liquid:adhesive (carbomer:NP700=1:5):moisturizing agent(propylene glycol):crosslinking agent(dihydroxyaluminum aminoacetate):cross-linking agent (tartaric acid)=3:30:0.3:0.3. The best preparation process is NP700and volatile oil dissolved in propylene glycol;the carbomer swelling in liquid over night after joining dihydroxyaluminum aminoacetate and tartaric acid, mixing, finally, the gel system with moisturizing system, and stir until a uniform cataplasm, paste, coated on the backing material(6cm*8cm), placed at room temperature two hours, cool, with lining, cutting, quality inspection, and packaging.(2) Transdermal research of the supplemented Lindera cataplasm in vitroBy using modified Franz diffusion cell, isolated female mice abdominal skin for transdermal test, tetrahydropalmatine cumulative penetration amount of twenty-four hours as index, selecting enhancers dosage and receiving solution. The results show that, when the dosage of borneol was2%, receiving fluid was15%ethanol saline, transdermal effect is best.3. Study on the quality standard of the supplemented Lindera cataplasmThe quality standard of the supplemented Lindera cataplasm was developed aeeording to the common requirement of patch described in the appendix of Chinese pharmacopoeia (Part One)(Edition2010) and specific charaeter of cataplasm. TLC was used to identify the Lindera, Radices saussureae, Cyperus rotundus, Corydalis rhizome, etc the qualitative in the supplemented Lindera cataplasm. Results of experiments show that the identification methods that can be identifiable, reliable, specific, negative control without interference;it should contain the amount of ointment not less then lOg per100cm2, Adhesion test according to adhesion assay (Appendix ⅩⅡE1st law) to take on the7th ball, shall comply with provisions;according to adhesion test assay (Appendix ⅩⅡE Seeond Law), cataplasm slipped to the time off should be more than40seconds;and study on shaping, weigh ivariation, microbial limit qualifieation;HPLC were used to determine the content of the tetrahydropalmatine in the supplemented Lindera cataplasm. According to the efxperimental results, the total amount of tetrahydropalmatine (C21H25NO4) should not be less than30μg. this provided a reliable basis for the quality control of the supplemented Lindera cataplasm.4. Preliminary pharmacodynamics study on the supplemented Lindera cataplasmSelect healthy Kunming female mice, according to the animal’s weight were randomly divided into normal control group, dysmenorrhea pathologic model group, positive control group, supplemented Lindera decoction group, supplemented Lindera cataplasm in high, medium, low group, a total of7groups, ten rats in each group. mice were given the same dose drug according to the group corresponding from the seventh day after making model. The positive control group and the supplemented Lindera decoction group orally administered, the supplemented Lindera cstaplasm in high, medium, low group, sticking abdominal delivery. Dysmenorrhea pain index was the writhing animal number and average writhing. Observe and record the average torsion body number and latency of mice. Preliminary study on effect of the supplemented Lindera cataplasm. The results show that, the supplemented Lindera cataplasm on dysmenorrhea model mice writhing response has obvious inhibiting effect.Conclusions:After extraction of the supplemented Lindera decotion and preparation process studies,we successfully made the supplemented Lindera cataplasm. The new formulation transdermal absorption in vitro, quality standard and preliminary pharmacodynamics study shows that the supplemented Lindera cataplasm forming good uniform, stable quality, achieve the expected objective.