| Muscle sour, joint pain is often faced in modern urban life one of the problems, in recent years, the incidence of neck, shoulder, waist increased year by year, the treatment of muscle and joint pain has become a public health problem. Western medicine effective in the treatment of pain at the same time, bring many adverse reactions, to bring new pain patients, treatment of social cost and the economic cost is higher. Chinese medicine treatment of muscle and joint pain with flexible methods, obvious curative effect and adverse reaction is relatively small, and the characteristics of the relatively low price. Ding Gui loose paste is the orthopaedic hospital in sichuan province of zheng & experience drugs used in one of the most common agents, clinical application of more than 30 years, the treatment of neck and shoulder, waist pain, as well as the middle and later periods of the injuries, trauma, soft tissue injuries of all kinds of pain curative effect is remarkable. This study combined with long-term clinical application foundation, in view of the neck, shoulder, waist the clinical characteristics, under the guidance of TCM theory, the theory of traditional Chinese medicine and modern percutaneous drug combination, it developed into a unique curative effect, convenient use, less adverse reaction, low cost, no trauma to the new Chinese medicine compound transdermal drug delivery preparation-Ding Gui gel preparation. This thesis mainly from the extraction process, prescription, promote through the optimization of the screening matrix, forming process, quality standard, stability studies, skin safety investigation, preliminary pharmacodynamics study, etc.1 Ding Gui gel paste matrix prescription and preparation technology research1.1 Ding Gui gel paste matrix skeleton of choiceIn appearance evaluation, the early adhesion force, adhesion force, peel strength as the evaluation index, combined with gel time, compares the several common skeleton composition study, select NP-700 as the skeleton of the prescription composition.1.2 The matrix prescription and preparation technology researchIn appearance evaluation, the early adhesion force, adhesion force, peel strength as the evaluation index, the single factor investigation method is used for paste Ding Gui gel matrix of preliminary screening, to determine the NP-700, carbomer, tartaric acid, glycerol, the suitable dosage range, by orthogonal experimental design, optimized the Ding Gui gel paste matrix prescription for:NP-700:gump aminoacetate:EDTA:kaolin:PVPP:glycerol:carbomer:PVP:tartaric acid:distilled water:extract= 6:0.24:0.1:5:2:2:30:0.1:0.1:49.36:5. Proved that the formula preparation Ding Gui gel paste appearance beautiful, the viscosity is better.1.3 Study of PreparationTo evaluation index and viscosity evaluation for appearance, Ding Gui gel preparation in the process of preparation of stirring speed, stirring time, it is concluded that:at room temperature and stir at a speed of 150 r/min 3 min, then stir 27 at a speed of 100 r/min min, total mixing time for 30 min, gel paste made of delicate appearance and viscosity.2 Ding Gui gel preparation and promote through screening study2.1 Qiang work alcohol in vitro percutaneous penetration test method is establishedBy investigating different animal skin and artificial skin Strat-m film, receive different medium, different experimental temperature on Ding Gui gel preparation of notopterygium alcohol in vitro percutaneous penetration behavior and the effect of establishing Ding Gui gel preparation of notopterygium alcohol in vitro percutaneous penetration experiment method:the Strat-M membrane for transdermal barrier,30% ethanol physiological saline for receiving medium, the experimental temperature of 37℃, magnetic stirring rotor speed 600 r/min.2.2 Promote transparent agent on Ding Gui gel preparation of notopterygium alcohol in vitro percutaneous penetration effectMethod is investigated using single factor investigation were 0.5%,1%,2%,3%, 4%,5% azone,2%,4%,6%,8%,6% propylene glycol,0.25%,0.5%,1%,1.5%,1% menthol to Ding Gui gel preparation and the effect of in vitro transdermal absorption results show that the azone (0.5%-2%), propylene glycol (4%～8%), menthol (0.5%-1.5%) within the scope of a certain proportion of Ding Gui gel preparation of notopterygium alcohol with different degree of its effect on promoting through, and the appearance, viscosity Ding Gui gel cream do not cause serious influence, oleic acid, NMP is not suitable for used as Ding Gui gel preparation of thoroughly.2.3 The orthogonal experiment design optimization Ding Gui gel preparation of composite and promote throughBasis of azone, propylene glycol, the single factor investigation result of menthol, with appearance grade, viscosity, notopterygium alcohol cumulative transdermal rate is a weighted average of the comprehensive index, the orthogonal experiment design method optimization and promote the resurrection through agent, according to the results by azone (0.5%)-propylene glycol (8%)-menthol (1.5%) of compound promote transparent agent on Ding Gui appearance and viscosity of the gel paste is affected, and promote the transdermal absorption performance is superior to the single and promote the use of transparent agent. With Ding Gui adjustable rubber paste paste comparative study on the in vitro transdermal test, according to gel preparation of transdermal absorption performance is superior to the rubber paste.3 Experimental study Ding Gui gel preparation process of amplificationIn combination with the practical situation of the mass production, the preparation process of laboratory to determine the amplification test, determine Ding Gui preparation technology of gel preparation are as follows:NP-700-6 g, f aminoacetate, EDTA of 0.1 g and 0.24 g 5 g,2 g PVPP kaolin glycerin 30 g, stir evenly, add extract as A phase,5 g to 0.1 g,2 g PVP, carbomer dissolved in distilled water 49.36 g for the night to make fully swelling, again to add tartaric acid 0.2 g as B phase, will add A phase B, at room temperature and stir at A speed of 150 r/min 3 min, then stir 27 at A speed of 100 r/min min, total mixing time for 30 min, coating on the non-woven fabric, covered embossing PE film, cutting, save.4 Research Ding Gui gel preparation of quality standardsAccording to the "Chinese pharmacopoeia" 2010 version a appendix emplastrum gel paste preparation under general rules and requirements, formulated the Ding Gui gel preparation of quality standards. TLC method of notopterygium, yanhusuo, live alone, combination, clove, cinnamon, angelica sinensis and rhizoma chuanxiong, radix angelicae has carried on the qualitative identification, the results show that the identification method is simple, reliable, strong specificity, negative without interference. To paste content, informs, adhesion, microbial limit inspection projects are studied, rules every 100 cm2 Ding Gui gel paste paste content should be not less than 10.0 g, adhesion test according to the China pharmacopoeia (2010 edition) assist the appendix E item first, second, the third method, the early adhesion force test Ding Gui gel preparation should be able to stick to 4 steel ball, the adhesion force test Ding Gui gel preparation within 1 h displacement distance should not be more than 4.0 cm, peel strength test Ding Gui gel paste 180 DHS peel strength should be not less than 0.04 kN/m. By high performance liquid chromatography (HPLC) method for Ding Gui gel preparation of notopterygium alcohol, to study the determination of the content of tetrahydropalmatine, according to the results, the rules of this product per piece of notopterygium of notopterygium alcohol (C21H22O5) shall not be less than 0.7 mg, rhizoma corydalis in tetrahydropalmatine (C21H25NO4) shall not be less than 0.18 mg. To control the immanent quality of Ding Gui gel cream provides a reliable basis.5 Ding Gui gel preparation stability studyAccording to the quality of the draft standard of three batch Ding Gui gel paste aluminum composite paper bag packaging, with Ding Gui gel paste appearance, identification, paste content, adhesion, microbiological examination and notopterygium alcohol Ding Gui gel preparation, determination of the content of tetrahydropalmatine as evaluation indexes, such as the six months of accelerated stability test and long term stability test, the stability of the preliminary investigation Ding Gui gel preparation. Results show that the Ding Gui gel paste under the condition of the package of sample is, three groups of samples in the temperature of 40 ℃+/-1℃, relative humidity of 75% plus or minus 5% of conditions, and under the normal temperature conditions,6 months, the appearance no change, identify responded positively and inspection, the paste content, adhesion, determination of content of qualified, microbial inspection check compliance. Sample stability within six months.6 Ointments and Ding Gui loose Ding Gui gel cream comparative study in vitro transdermal absorptionDing Gui gel preparation and Ding Gui loose paste, according to the results of the comparative study on the in vitro transdermal test in 2,4,6,8,12,24 and 48 h, cumulative transdermal rate of gel preparation were Ding Gui loose paste of 1.22, 1.21,1.51,1.57,1.76,2.14,1.76 times, during the period of 2 h-48 h, Ding Gui gel paste the transdermal rate is about Ding Gui loose paste 2 times, Ding Gui gel preparation within 48 h cumulative transdermal rate of about 64%. Ding Gui gel preparation of transdermal absorption effect is Ding Gui loose cream better.7 Ding Gui gel paste the security of the experimental studyThrough the skin irritation experiment study shows that in Japan big-eared white rabbits as the research object, Ding Gui gel paste single or continuous administration, rabbit skin were observed thinning edema, pigmentation, permeability drops of blood, skin, weight is unusual, Ding Gui gel preparation does not cause the rabbit skin stimulus response; Experimental study shows that the skin allergy with white fur guinea pigs as the research object, Ding Gui gel preparation, after repeated dose not cause guinea pig skin allergic reaction, there is no systemic reaction, found no Ding Gui gel paste has obvious sensitization.8 Ding Gui gel preparation of preliminary pharmacodynamics experimentBy investigating Ding Gui gel preparation of acetic acid in mice body torsion reaction and to stimulate mice pain reaction and hot plate pain caused by experiments of formalin in mice and the effect of preliminary think Ding Gui gel preparation had obvious analgesic action. Ding Gui gel preparation high dose group, the equivalent dose group, Ding Gui loose paste can inhibit in different degrees stimulation caused by hot plate pain reaction in mice, and the drug effect after 90 min obviously increased (P< 0.05). Ding Gui gel preparation high dose group, the equivalent dose groups, Ding Gui loose paste could obviously against I phase nerve pain caused by formaldehyde, II phase inflammatory pain reaction (P< 0.05). Dante laurel gel paste each dose group and Ding Gui loose paste changes to the body torsion reaction times there was no significant difference compared with control group.By anti-inflammatory experiments found that Ding Gui gel cream every dose group only against the effect trend of mouse ear swelling induced by xylene, compared with model group had no significant difference. Ding Gui gel cream equivalent dose group and high dose group were to some extent to reduce carageen glue effect on rats foot swelling (P< 0.05).Through the experimental research, a preliminary thought Ding Gui gel paste have certain analgesic and anti-inflammatory effects.9 Preliminary mechanism research of the analgesic and anti-inflammatory effects of Ding Gui gel pasteBy investigating Ding Gui gel preparation on foer Ma Linzhi pain model in mice and TNF in serum IL-1-alpha content, the influence of initial think Ding Gui gel preparation high dose group can significantly reduce the animal model of serum IL-1 content (P< 0.05), Ding Gui gel preparation high dose group, the equivalent dose group and Ding Gui loose paste group can significantly reduce the model animal in the serum TNF alpha levels (P< 0.05, P< 0.01).By investigating Ding Gui gel paste diagonal carageen glue foot swelling model rats serum IL-1 and the influence of TNF alpha content, preliminary think Ding Gui gel paste each dose group and Ding Gui loose paste has a lower animal model is the trend of the content of serum IL-1, Ding Gui gel preparation high dose group and Ding Gui loose paste can significantly reduce the model animal in the serum TNF alpha content (P< 0.05).By investigating Ding Gui gel paste model of adjuvant arthritis rats left and right rear ankle joint circumference, and serum IL-1, TNF alpha, IgG, IgM,5-HT, PGE2, NO content, the influence of initial think Ding Gui gel preparation high dose group, the equivalent dose group, Ding Gui loose paste have certain effects on the above indexes, performance for:Ding Gui equivalent dose group and high dose group, Ding Gui Ding Gui adjustable cream group after the right and left of model rats could improve the abnormality of ankle joint swelling, Ding Gui IgG levels of model rats of high dose group increase improved significantly (P< 0.05), Ding Gui equivalent dose group and high dose group, Ding Gui Ding Gui adjustable cream group increased NO content of model rats only decrease trend and there was NO significant difference.By Ding Gui gel paste analgesic, anti-inflammatory mechanism to carry on the preliminary study, anti-inflammation and analgesic action of drugs may not play to reduce foer Ma Linzhi pain model and carageen glue foot swelling model animal serum IL-1 and the content of TNF alpha, and reduce the model of adjuvant arthritis animal serum IL-1, IgG, IgM, NO and other factors related to the content.
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