| Fufangjizhi Capsule is pure Chinese herbal oral drug, derived from traditional Chinese medicine prescription and by its appropriate combination of addition and subtraction of according to Chinese medicine theory and clinical practices. The drug is prepared by extracting from six kinds of TCM including Radix et Rhizoma Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Angelica Dahuricae, Radix et Rhizoma Asari, Fructus Tribuli, and Scorpio all indexed in the Chinese Pharmacopoeia (Edition 2005). The prescription is reasonable and innovative, mainly for the treatment of migraine, dizzy and recurrent headache.Fufangjizhi Capsule belongs to the sixth type of new traditional Chinese medicine. The pharmaceutical research contents including preparation process and quality control standards were established in accordance with the procedures for examination and approval of new drugs. The capsule form was selected as the agents. Furthermore, further study of preparation process, quality standards, stability, etc were developed. The results are as follows:1,Research of the preparation processThe preparation process of Fufangjizhi Capsule:By prescriptions, Radix et Rhizoma Salviae Miltiorrhizae of 250 g were powered. Radix et Rhizoma Asari, Rhizoma Chuanxiong and Radix Angelica Dahuricae were altogether immersed with 5 times water in the distill tank for 12 h, then distilled for 6 h to give volatile oil.β-cyclodextrin was ground uniformly in 2 times water on the bath kept at 45℃, then mixed with the ethanol solution of volatile oil [the ratio of volatile oil (ml) andβ-cyclodextrin (g) was 1: 8] in mortar by manual grinding for 3 h to batter and dried at 40℃. The residue of Radix et Rhizoma Salviae Miltiorrhizae was extracted with 7 times 90% ethanol under reflux for 1h. The extraction solution was concentrated in vacuum to dry extract which was then ground into fine powder. Fructus Tribuli, Scorpio and the residues after removing the volatile oil and the ethanol extract were immersed with 8 times water in the distill tank for 1 h, then distilled 3 times each for 2 h. The decoction and that after extracting the volatile oil were combined, concentrated to the relative density of 1.10-1.15 (25℃), precipitated by adding 95% alcohol to a concentration of 75% still for 12 h, filtrate, and concentrated to dry extract. The extract was ground into fine powder, added appropriate starch, mixed uniformly with the fine powder obtained before andβ-cyclodextrin inclusion complex, dried (<60℃) and mounted 1000 capsules.2,Research of quality standardIn accordance with the requirements for capsule in Chinese Pharmacopoeia (Edition 2005) of, the water content, the gross deviation, disintegration, heavy metals, arsenic salt and the microorganism limit were determinated. The results are in accordance with those in Chinese Pharmacopoeia.Under identification item, by the TLC experiments of Radix et Rhizoma Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Angelica Dahuricae, Radix et Rhizoma Asari and Fructus Tribuli, the ones of Radix et Rhizoma Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Angelica Dahuricae and Radix et Rhizoma Asari were ultimately selected as the qualitative identification for the preparation. The experimental results suggested that the spots on TLC are clear, characteristic, reproducible, and no negative interference. The methods are suitable for the qualitative identification of Fufangjizhi Capsule.Under content determination item, the assay of salvianolic acid B and its methodological study in Fufangjizhi Capsule were carried out by HPLC experiments performed on column VP-ODS (4.60×250 mm, 5μm). The column temperature was kept at 35℃; the mobile phase was methanol-acetonitrile-formic acid-water (30: 9: 1: 60); the rate was 1.0 ml/min; the detection wavelength was set at 286 nm。The result showed that salvianolic acid B had good linear relationship between the injection volume (X,μg) and peak area (Y) during the range of 0.6048~1.4112μg. The linear equation was Y = -433591.3+1396426.091X (r = 0.9999); The average recovery rate of the method was 97.02%; RSD = 1.03% (n = 5)。The content limit of salvianolic acid B in Fufangjizhi Capsule was defined as no less than 10.0 mg per capsule. The method is simple, accurate, reproducible and can be used as quality control of the preparation.In addition, the content determination methods and methodological study of the toxic ingredient, aristolochic acid in Fufangjizhi Capsule were also investigeted. HPLC experiment was performed on column VP-ODS (4.60×250 mm, 5μm). The mobile phase was acetonitrile-1% glacial acetic acid-water (39: 61); the rate was 1.0 ml/min; the detection wavelength was set at 317 nm; the column temperature was at 35℃. Theoretical plate number calculated by aristolochic acid is no less than 2000. The detection limit was 8 ng. Aristolochic acid should not be detected at the sample amout of 4.6 g.3,Research of the stabilityIn accordance with the procedures for examination and approval of new drugs, the stability of three batches of Fufangjizhi Capsules was investigated by the normal temperature test and the acceleration test. The items of the preparation characters, appearance, the gross deviation, disintegration, the microorganism limit, the qualitative identification, the content determination, etc were also studied in accordance with the draft requirements. By the normal temperature test and the acceleration test each for 6 months, all indications are in line with requirements. It showed that the preparation was stable and the stability was good in the storage life.The results showed that the preparation procedure of Fufangjizhi Capsule is reasonable in technics, controllable in quality and good in stability. The research provided a whole pharmaceutical data for the submission of Fufangjizhi Capsule. |
