| Rheumatic disease,which is with slow recovery,recurrent attacks and the possibility of mutilation because of malpractice or long disease-process, has caused great damage and burden to the sufferers and their families.Most of the articular disease is with a chronic and advanced process,and he incidences increased while mankind duration of life extended.Western medicine still doesn't have especially effective radical cure method clinically.Some of the drugs such as nonsteroidal antiinflammatory drugs,glucocorticoid, amethopterin,and cyclophosphamide can only be used to alleviate the symptoms, but the long-term effect is not ideal and the harm and side effect is hard to be accepted.Therefore,it' s prospective to exploit traditional Chinese compound preparation to treat Rheumatic disease.LiaoJin plastic is developed from clinical empirical formula and improved from traditional praeparatum LiaoJin mastic in our hospital.It has effectiveness of promoting blood circulation and removing blood stasis and detumescence and acesodyne,It is used to treat rheumatic disease and trauma disease.The dosages of hospital preparations are great,and the clinical curative effect is satisfactory,but there exists some disadvantages like deficiency of basic research,outdated of praeparatum artwork,incomplete quality standard,big dosage and inconvenient to take along and use.The objective in our study is to develop the hospital traditional preparation into a new Chinese medicine per-cutem administration preparation with modern science methods.In this way,the bioavailability is improved,and the evaporation of skin-surface moisture is reduced.In addiction,the hydration and the effect of dissolving the horniness is promoted in order to release the medicine through the corneal layer and improve the curative effect,and the schlepping and usage have become convenient.The new drug has been developed according to the new drug development principal of national accreditation center.And the results are as follows:1.The study of LiaoJin plastic extraction and decontamination methodology.With the considerations of component and pharmacological effects of every decoction pieces,and practical production,environment protection demands, the extraction methodology of angelica-root naphtha was investigated first. The angelica-root was broken into coarse powder,and dipped in decuple water for a night,and extracted by vapour distillation method until the naphtha did not increase any more,but the naphtha content was only 0.04%.So the experimental extraction effect was not ideal,needless to say the production. So the way of extracting the naphtha first and coumarin secondly is unfeasible. So literature proved that as for the active ingredient extraction effect,the ethanol extraction is better than water extraction,and active ingredient has positive correlation with the soothing effect.At the angle of industrialization and pharmacology,angelica-root should be mixed with other medicinal powders before ethanol extraction.Ethanol extraction is used for the extraction of Rhubarb,shinyleaf pricklyash root,and angelica-root. Emodin and ethanol extract were chosen as index,and orthogonal design L9(34) was used for extraction-parameters screening.70%ethanol with added to medicinal materials was finally chosen to be done the extraction twice.At the first time sextuple 70%ethanol wasadded and the extraction time was 1.5 hours,and at the second time the extraction time was changed into 1 hour. Water extraction is used for the extraction of radices paeoniae rubra,radices scutellariae and brazilwood(radices scutellariae was added when the water was boiling).Peoniflorin and ethanol extract yield were chosen as indexs, and orthogonal design L9(34) was used for extraction-parameters screening. It was proved that,under the conditions of tenfold water added with medicinal materials and 1.5-hour marinating time,Peoniflorin content and ethanol extract yield were the highest.So the condition was the best water extraction methodology.Impurity subtraction research was carried on in water extraction methodology,with a series of rationality verification and a comparison among water extraction with ethanol precipitation,natural precipitation, centrifugation and so on.Ultimately,the methodology of extraction with 70% ethanol precipitation was chosen,and according to the peoniflorin in water extraction liquid,concentrate and ethanol precipitation liquid,the feasibility of methodology was verificated.2.The preparation methodology study of LiaoJin plasticWith plastic formation time and appearance quality as index,by monothetic investigation and orthogonal test,the preparation methodology of LiaoJin plastic was optimized.Firstly,by monothetic investigation,the composition of plastic formation material was chosen from PVA-1788,PVA-0588,PVA-124, rhizoma bletillae glue,glycerin,ethanol,acetone,azone,and distilled water and other base materials.Then orthogonal test was used to optimize the main base materials dosages which influenced the plastic.The best base materials proportion was PVA-124:ethanol:acetone:distilled water=1:4:2:10.3.The screening of LiaoJin plastic per-cutem accelerant and the investigation of in-vitro per-cutem infiltration behavior.In-vitro per-cutem absorption test was used to study the per-cutem infiltration behavior of the preparation.Infiltration medium,in-vitro cutis cryopreservation time,and in-vitro per-cutem infiltration behavior influence which single and composite per-cutem accelerant exerted to the peoniflorin in LiaoJin plastic were respectively investigated.With fitting degree (correlation coefficient) as index,zero-degree,Higuchi and other different fitting equation in the application of the preparation was investigated. According to the experiment,propanediol:borneol:azone(5%:8%:3%) was temporarily decided to be the chemical infiltration accelerant.With correlation coefficient as index,Higuchi equation had the best fitting effect, and its correlation coefficients were all above 0.95.Under the influence of different infiltration accelerants,peoniflorin per-cutem infiltration behaviors all fitted to Higuchi drug-release equation.4.The quality standard study of LiaoJin plastic.In the study of quality standard,preparation apparence quality, comparatively consistency,PH value,plastis formulation time,95%ethanol extracta,ablazing leavings,acid-insoluble ash,total solid quantity and so on were measured.Traditional TLC and micro emulsion TLC were used for determine-the-nature identification.Traditional TLC methods were established for the identification of rhubarb,radices paeoniae rubra, angelica root,brazilwood,micro emulsion TLC methods were established for the identification of radices scutellariae,brazilwood,Zanthoxylum nitidum DC.After repetitive experiments,HPLC methods were established for the assayings of aloe-emodin,rhein,chrysophanic acid,emodin,rheochrysidin (contained in the monarch drug in a prescription),and peoniflorin(contained in radices paeoniae rubra),GC methods were established for the assayings of the volatile matters including borneol,isoborneol,and menthol in camphor and mint,and methodology investigation was carried out.The result proves that,the methods used for the assayings are simple,reliable,and their repeatabilities are high,and they provide theory evidence for product quality control and medicine curative effect assurance.5.The stability study of LiaoJin plastic.By the method of the stability acceleration test recommended by FDA,three batches samples were conserved under the condition of 35～40℃and RH75%±5%,and sampling inspection was done in the 0th,1th,2th,3th,6th month,and every index conformed to specification.It indicated that,the initiative stability of sample plastic bottle which was placed under that condition for six month was high.In the study of application of Chinese traditional medicine UV spectra group method in this preparation influencing factor test,the result indicated that this preparation was unstable at high temperature(80℃),and stable at high humidity or under the highlight irradiation.This result provides reference for new-drug conservation condition and wrapper.6.The safety evaluation of LiaoJin plastic cutaneous covering administration.Acute toxicity test of cutaneous covering administration indicated that the rats'skin,pelage,eyes,mucosa,breathing and behaviors were all normal during and seven days after the administration.No matter in the integrity and breakage cutis administration,the situs of applichation of medicine slightly turned red,the rest part and system shown non apparent abnormality, and no death,there was no significant difference from control group.The result showed that the precutaneous administration of the preparation had no acute toxicity,and the safety was high.The skinirritation tests of single or multiple administration to the integrity or breakage cutis indicated that there was no phenomenons of distinct erythema,edema,pigmentation,bleeding spot,pachulosis or over-thin cutis.Histological examination showed no pathological change,and skin irritation was mild.The cutis sensitivity test indicated that the guinea pigs given LiaoJin plastic had no erythema,edema or other curis allergic reactions,asthma,astasia,shock or other whole-body allergic reactions.The results indicate that,basically,LiaoJin plastic has no curls allergic reaction. |
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