CN104814944A - Transdermal patch for preventing and treating lumbar disc herniation and preparation method thereof - Google Patents
Transdermal patch for preventing and treating lumbar disc herniation and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a transdermal patch for preventing and treating lumbar disc herniation and a preparation method thereof. The transdermal patch includes a back lining layer, a drug-containing substrate layer fixed on the back lining layer and an anti-sticking layer covering the drug-containing substrate layer. The drug-containing substrate layer includes 15-45 parts of a hydrogel substrate, 15-45 parts of a volatile oil part, 30-90 parts of an ethanol refined extract and 8-24 parts of a transdermal penetration enhancer. The traditional Chinese medicines of the transdermal patch are matched scientifically and reasonably and the transdermal patch has a large carrying capacity. A test result proves that the hydrogel transdermal patch has significant effects of inflammation resistance, blood activation and pain relieving, has an excellent effect of treating the lumbar disc herniation, has a long-action slow-releasing effect of slowly releasing active drug components durably, is convenient to use, and is free of stimulation and allergy on skin.
Description
Technical field:
The present invention relates to a kind of Chinese medicine composition and exterior-applied liquid medicine gel adhesive thereof, be specifically related to a kind of to there is transdermal patch preventing and treating prolapse of lumbar intervertebral disc and preparation method thereof.
Background technology
Prolapse of lumbar intervertebral disc means because lumbar nucleus pulposus gives prominence to its peripheral nerve tissue of compressing and the series of symptoms that causes.Clinical statistics shows, it is one of the most common illness of Orthopaedics Clinic that lumbar intervertebral disc prominent (taking off) goes out disease, also be the most common reason of lumbago and skelalgia, the most common with persistence lower back dull pain clinically, alleviate with horizontal position, stand, aggravate, can stand in the ordinary course of things, and allow that waist appropriateness is movable and slowly walk, mainly caused by mechanical pressure.2 weeks at least persistent period, elder can reach the several months, even several years.Another kind of pain is waist spasm sample severe pain, not only falls ill suddenly hurried, and is difficult to stand more, and Non-staying in bed is had a rest can not.This is mainly caused by ischemic neuronal root inflammation, i.e. vertebral pulp outstanding pressuring neural root suddenly, causes root blood vessel pressurized and present a series of changes such as ischemia, congestion, weary oxygen and edema simultaneously, and can last for days to several weeks.Also show as lower limb radiating pain clinically in addition, numb limbs and tense tendons, the symptoms such as muscular paralysis, have a strong impact on the life of people.
With advancing age, people's skeleton calcium loss, in addition seating and standing posture is not right, easily there is the diseases such as prolapse of lumbar intervertebral disc in lumbar intervertebral disc, have a strong impact on the live and work of people, for lumbar intervertebral disc protrusion disease, the general Therapeutic Method adopting operation, there is the shortcomings such as ailing and expense height, Chinese medicine is preventing and treating advantage especially unique in prolapse of lumbar intervertebral disc, but the Chinese medicine being used for the treatment of prolapse of lumbar intervertebral disc at present greatly mainly with oral be main, there is first pass effect and gastrointestinal destroys, the problems such as bioavailability is low.
Therapy characteristics and the advantage of percutaneous absorption patch are, transdermal drug delivery system can avoid the first pass effect of liver and medicine in gastrointestinal deactivation, the absorption of medicine, not by the impact of gastrointestinal factor, reduces the individual variation of medication, maintains constant drug effect haemoconcentration or physiological effect.
Summary of the invention
Goal of the invention: the object of the invention is for the deficiencies in the prior art, there is provided a kind of easy to use, curative effect is continual and steady, therapeutic effect has the transdermal patch preventing and treating prolapse of lumbar intervertebral disc significantly, and another object of the present invention is to provide the preparation method of this transdermal patch.
Technical scheme: in order to realize above object, the technical scheme that the present invention takes is:
A kind of have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, it is characterized in that, the adherent layer comprising backing layer, be fixed on the pastille hypothallus on backing layer and cover on pastille hypothallus, described pastille hypothallus comprises hydrogel matrix 15 ~ 45 parts, volatile oil part 15 ~ 45 parts, ethanol refine extract 30-90 part and transdermal penetration enhancer 8 ~ 24 parts;
Described volatile oil part is prepared by following method:
(1) Radix Angelicae Sinensis 20 ~ 40 parts is got, Radix Codonopsis 10 ~ 30 parts, 15 ~ 30 parts, Flos Carthami, Radix Salviae Miltiorrhizae 15 ~ 30 parts, Rhizoma Chuanxiong 15 ~ 30 parts, Rhizoma Drynariae 10 ~ 25 parts, Rhizoma Cibotii 5 ~ 20 parts, Rhizoma Osmundae 4 ~ 24 parts, the Cortex Eucommiae 10 ~ 30 parts, Radix Dipsaci 10 ~ 40 parts, Rhizoma Corydalis 10 ~ 40 parts, Rhizoma Zingiberis 20 ~ 40 parts, Radix Angelicae Pubescentis 10 ~ 30 parts, Radix Dipsaci 10 ~ 20 parts, Radix Achyranthis Bidentatae 10 ~ 40 parts, the Radix Paeoniae Alba 5 ~ 25 parts, Caulis Sinomenii 6 ~ 24 parts, the Radix Astragali 20 ~ 40 parts, Semen Cuscutae 10 ~ 20 parts, Caulis Spatholobi 20 ~ 40 parts, Herba Pyrolae 10 ~ 25 parts, the Chinese medicine composition of Herba Lycopodii 15 ~ 45 parts and Scorpio 5 ~ 10 parts composition, add the soak by water 2 ~ 3 times of Chinese medicine composition gross weight 8 ~ 15 times amount, and collect with volatile oil extractor and obtain volatile oil part, merge decocting liquid and obtain concentrate at 30 ~ 70 DEG C of concentrating under reduced pressure,
(2) get the concentrate that step (1) obtains and add ethanol, reflux, extract, 2 ~ 3 times, each 1 ~ 2 hour, merge ethanol extraction and concentrate, obtain ethanol concentrate;
(3) get macroporous adsorptive resins on ethanol concentrate that step (2) obtains, be the ethanol elution of 50% ~ 70% by volumetric concentration, merge 60% ethanol elution, concentrated, dry that extract be refined by ethanol.
Preferably, above-described have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, described Chinese medicine composition by Radix Angelicae Sinensis 40 parts, Radix Codonopsis 30 parts, 20 parts, Flos Carthami, Radix Salviae Miltiorrhizae 30 parts, Rhizoma Chuanxiong 25 parts, Rhizoma Drynariae 20 parts, Rhizoma Cibotii 10 parts, Rhizoma Osmundae 16 parts, the Cortex Eucommiae 20 parts, Radix Dipsaci 35 parts, Rhizoma Corydalis 20 parts, Rhizoma Zingiberis 40 parts, Radix Angelicae Pubescentis 16 parts, Radix Dipsaci 16 parts, Radix Achyranthis Bidentatae 30 parts, the Radix Paeoniae Alba 25 parts, Caulis Sinomenii 18 parts, the Radix Astragali 40 parts, Semen Cuscutae 20 parts, Caulis Spatholobi 30 parts, Herba Pyrolae 10 parts, Herba Lycopodii 20 parts and Scorpio 6 parts composition.
Preferably, above-described have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, and described hydrogel matrix comprises 5 ~ 20 parts of adhesive, 20 ~ 40 parts of framework materials and 10 ~ 30 parts of wetting agents.
Preferably, above-described have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, and described adhesive is sodium alginate or carboxymethyl cellulose.
Preferably, above-described have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, and described framework material comprises polyvinyl alcohol or PVP K30.
Preferably, above-described have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, and described wetting agent comprises glycerol or PEG400.
Preferably, above-described have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, and described transdermal penetration enhancer is one or more in azone, propylene glycol or menthol.
The preparation method with the transdermal patch preventing and treating prolapse of lumbar intervertebral disc of the present invention, comprises the following steps:
(1) Radix Angelicae Sinensis 20 ~ 40 parts is got, Radix Codonopsis 10 ~ 30 parts, 15 ~ 30 parts, Flos Carthami, Radix Salviae Miltiorrhizae 15 ~ 30 parts, Rhizoma Chuanxiong 15 ~ 30 parts, Rhizoma Drynariae 10 ~ 25 parts, Rhizoma Cibotii 5 ~ 20 parts, Rhizoma Osmundae 4 ~ 24 parts, the Cortex Eucommiae 10 ~ 30 parts, Radix Dipsaci 10 ~ 40 parts, Rhizoma Corydalis 10 ~ 40 parts, Rhizoma Zingiberis 20 ~ 40 parts, Radix Angelicae Pubescentis 10 ~ 30 parts, Radix Dipsaci 10 ~ 20 parts, Radix Achyranthis Bidentatae 10 ~ 40 parts, the Radix Paeoniae Alba 5 ~ 25 parts, Caulis Sinomenii 6 ~ 24 parts, the Radix Astragali 20 ~ 40 parts, Semen Cuscutae 10 ~ 20 parts, Caulis Spatholobi 20 ~ 40 parts, Herba Pyrolae 10 ~ 25 parts, the Chinese medicine composition of Herba Lycopodii 15 ~ 45 parts and Scorpio 5 ~ 10 parts composition, add the soak by water 2 ~ 3 times of Chinese medicine composition gross weight 8 ~ 15 times amount, and collect with volatile oil extractor and obtain volatile oil part, merge decocting liquid and obtain concentrate at 30 ~ 70 DEG C of concentrating under reduced pressure,
(2) get the concentrate that step (1) obtains and add ethanol, reflux, extract, 2 ~ 3 times, each 1 ~ 2 hour, merge ethanol extraction and concentrate, obtain ethanol concentrate;
(3) get macroporous adsorptive resins on ethanol concentrate that step (2) obtains, be the ethanol elution of 50% ~ 70% by volumetric concentration, merge 60% ethanol elution, concentrated, dry that extract be refined by ethanol;
(4) preparation of hydrogel matrix: get adhesive and framework material adds water, place 24 hours fully swelling, water-bath mix and add wetting agent, abundant stirring and evenly mixing, obtaining transparent sticky hydrogel matrix;
(5) get step (1) volatile oil part 15 ~ 45 parts and refine extract 30 ~ 90 parts with step (3) ethanol, be scattered in 15 ~ 45 parts of hydrogel matrixes that step (4) prepares, add transdermal penetration enhancer 8 ~ 24 parts, mix homogeneously, ultrasonic removing bubble, coat while hot on backing layer, after drying, be covered with adherent layer, to obtain final product.
Preferably, the above-described preparation method with the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, the adhesive described in step (4) is sodium alginate or carboxymethyl cellulose; Described framework material is polyvinyl alcohol or PVP K30; Described wetting agent is glycerol or PEG400.
Preferably, the above-described preparation method with the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, the transdermal penetration enhancer described in step (5) is one or more in azone, propylene glycol or menthol.
The present invention adopts the proportioning of orthogonal experiment to adhesive, framework material and wetting agent to screen, position chemical property is refined for benchmark with Chinese medicine composition volatile oil and ethanol extraction, and with the percutaneous permeation of hydrogel matrix, first viscous force and organoleptic indicator for inspection target, filter out above-mentioned optimum substrate proportioning.The present invention adopts hydrogel matrix, and without skin irritation and sensitization in preparation process, for water soluble drug, drug loading can increase greatly, is more conducive to drug transdermal, and bioavailability improves, better efficacy.
Preferably, above-described have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, and described adhesive comprises sodium alginate and carboxymethyl cellulose and sodium salt thereof.The present invention is according to the chemical property of Chinese medicine composition effective ingredient, contrast experiment shows: select sodium carboxymethyl cellulose to have good stability, can thick stable colloidal solutions be formed after dissolving in water, with other water-soluble glue or resin, there is the advantages such as good compatibility; Select sodium alginate to have viscosity low, fine size, attached wall is good, steady performance.
Preferably, above-described have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, and described framework material comprises polyvinyl alcohol and PVP K30.The present invention is based on the chemical property of Chinese medicine composition effective ingredient, and contrast experiment shows, the easy film forming of polyvinyl alcohol, the good mechanical performance of its film, and have good cohesive force with hydrophilic fiber; PVP K30 also has the advantages such as film property, caking property and good hygroscopicity in addition, has excellent solubility property and physiological compatibility to effective ingredient.
Preferably, above-described have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, and described wetting agent comprises glycerol and PEG400.The present invention shows according to contrast and experiment, there is when selecting glycerol and PEG400 the better compatibility of effective ingredient of refining extract with the volatile oil part of Chinese medicine composition of the present invention and ethanol, and there is better hygroscopicity, humectation and the property of softening.
The present invention follows the tracks of according to tcm field and modern isolation and purification method and pharmacological evaluation, and experimental result shows, the volatile oil part of Chinese medicine compound of the present invention has strong detumescence, antiinflammatory, relieves the pain, and the effect such as to invigorate blood circulation, achieves good technique effect.
Preferably, above-described have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, and described transdermal penetration enhancer is one or more in azone, propylene glycol or menthol.The present invention is with percutaneous absorbtion speed during transdermal test in vitro, unit are transit dose and accumulate through percentage rate for index, filters out penetration enhancer effective ingredient to best short saturating effect: azone, propylene glycol and menthol according to lots of comparing experiments.
Beneficial effect: provided by the invention have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc and compared to the prior art have the following advantages:
1, provided by the invention have prevent and treat prolapse of lumbar intervertebral disc Chinese medicine composition, according to the pathogenesis of theory of Chinese medical science and prolapse of lumbar intervertebral disc, by great many of experiments screening Chinese medicine composition, prescription adopts invigorates blood circulation (as Radix Angelicae Sinensis, Flos Carthami, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong), circulation of qi promoting, antiinflammatory (the Radix Paeoniae Alba, Caulis Sinomenii, the Radix Astragali, Caulis Spatholobi, Herba Pyrolae, Scorpio etc.), detumescence relieves the pain, muscle relaxing collaterals activating (Rhizoma Drynariae, Rhizoma Cibotii, Rhizoma Osmundae, the Cortex Eucommiae, Radix Dipsaci, Rhizoma Corydalis, Radix Angelicae Pubescentis, Radix Dipsaci, Radix Achyranthis Bidentatae, Semen Cuscutae, Herba Lycopodii), promote that blood follows bad, the Chinese medicine scientific matching increasing skeleton blood flow forms, experimental result shows that Chinese medicine composition provided by the invention has the effect of well preventing and treating prolapse of lumbar intervertebral disc, and by the preferred preparation capable of permeating skin of the present invention, can absorb by rapid transdermal, play lasting drug effect.
2, the transdermal patch with the effect preventing and treating prolapse of lumbar intervertebral disc provided by the invention, by great many of experiments screens hydrogel matrix, volatile oil active site, ethanol refine extract and transdermal penetration enhancer composition and outfit, experimental result shows, the hydrogel matrix adopted has larger drug loading (refine extract to volatile oil part and ethanol and all have desirable drug loading), without skin irritation and sensitization in preparation process, be not easy pollution clothes, also have well short oozing property for water soluble ingredient; And the sodium carboxymethyl cellulose that the present invention selects, sodium alginate, polyvinyl alcohol, PVP K30, glycerol and PEG400 screen through orthogonal experiment, reasonable mixture ratio, technique is clear and definite, and the substrate outward appearance of formation, adhesion and percutaneous permeation are all excellent;
3, transdermal patch provided by the invention, extract refined by volatile oil part and the ethanol of pastille hypothallus, on the basis of Chinese medical theory and prolapse of lumbar intervertebral disc Mechanism Study, choose rational composition of prescription to extract, carry out removing crudely and store essence gained by modern separation and purification means, and component analysis and pharmacodynamic study are carried out to it, filter out volatile oil active site and ethanol elution active site, active component is clear and definite, there is good pain relieving, antiinflammatory, the effects such as blood circulation promoting and blood stasis dispelling, and analyze for its effective ingredient, according to physicochemical property and the Transdermal absorption feature of effective ingredient, make transdermal delivery system, drug absorption can be impelled, rapid-onset, slow releasing, bioavailability is high, to prolapse of lumbar intervertebral disc shape, there is good improvement result.
Detailed description of the invention
Below in conjunction with specific embodiment, illustrate the present invention further, these embodiments should be understood only be not used in for illustration of the present invention and limit the scope of the invention, after having read the present invention, the amendment of those skilled in the art to the various equivalent form of value of the present invention has all fallen within the application's claims limited range.
Embodiment 1
The preparation method with the transdermal patch preventing and treating prolapse of lumbar intervertebral disc of the present invention, comprises the following steps:
(1) Radix Angelicae Sinensis 40 parts, Radix Codonopsis 30 parts is got, 20 parts, Flos Carthami, Radix Salviae Miltiorrhizae 30 parts, Rhizoma Chuanxiong 25 parts, Rhizoma Drynariae 20 parts, Rhizoma Cibotii 10 parts, Rhizoma Osmundae 16 parts, the Cortex Eucommiae 20 parts, Radix Dipsaci 35 parts, Rhizoma Corydalis 20 parts, Rhizoma Zingiberis 40 parts, Radix Angelicae Pubescentis 16 parts, Radix Dipsaci 16 parts, Radix Achyranthis Bidentatae 30 parts, the Radix Paeoniae Alba 25 parts, Caulis Sinomenii 18 parts, the Radix Astragali 40 parts, Semen Cuscutae 20 parts, Caulis Spatholobi 30 parts, Herba Pyrolae 10 parts, the Chinese medicine composition of Herba Lycopodii 20 parts and Scorpio 6 parts composition; Add the soak by water 3 times of Chinese medicine composition gross weight 12 times amount, and collect with volatile oil extractor and obtain volatile oil part, merge decocting liquid and obtain concentrate at 60 DEG C of concentrating under reduced pressure;
(2) get the concentrate that step (1) obtains and add ethanol, reflux, extract, 3 times, each 2 hours, merge ethanol extraction and concentrate, obtain ethanol concentrate;
(3) get macroporous adsorptive resins on ethanol concentrate that step (2) obtains, be the ethanol elution of 50% ~ 70% by volumetric concentration, merge 60% ethanol elution, concentrated, dry that extract be refined by ethanol;
(4) preparation of hydrogel matrix: get sodium alginate 5 parts, PVP K30 10 parts, adds 20 parts of water after mixing, leave standstill 24 hours, fully swelling, obtains gel A; Get polyvinyl alcohol 5 parts, add 15 parts of water, leave standstill 24 hours, dissolve in 95 DEG C of water-baths after fully swelling, obtain gel B.Mixed gel A and gel B in 70 DEG C of water-baths, be stirred to gel mix homogeneously, add 5 parts of PEG400s, abundant stirring, add the ethanol that in step (1), gained volatile oil part and step (3) obtain afterwards and refine extract, be stirred to abundant mixing, finally add 1 part of azone, 3 parts of propylene glycol, after abundant stirring and evenly mixing, namely obtain pastille hypothallus.
(5) the pastille hypothallus getting step (4) gained is coated on backing layer while hot, is covered with adherent layer after drying, cuts into suitable size, packs and get final product.
Embodiment 2
Have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, comprise backing layer, pastille hypothallus and adherent layer, its preparation method comprises the following steps:
(1) get (1) and get Radix Angelicae Sinensis 40 parts, Radix Codonopsis 30 parts, 30 parts, Flos Carthami, Radix Salviae Miltiorrhizae 30 parts, Rhizoma Chuanxiong 30 parts, Rhizoma Drynariae 25 parts, Rhizoma Cibotii 20 parts, Rhizoma Osmundae 24 parts, the Cortex Eucommiae 30 parts, Radix Dipsaci 40 parts, Rhizoma Corydalis 40 parts, Rhizoma Zingiberis 40 parts, Radix Angelicae Pubescentis 30 parts, Radix Dipsaci 20 parts, Radix Achyranthis Bidentatae 40 parts, the Radix Paeoniae Alba 25 parts, Caulis Sinomenii 24 parts, the Radix Astragali 40 parts, Semen Cuscutae 20 parts, Caulis Spatholobi 40 parts, Herba Pyrolae 25 parts, the Chinese medicine composition of Herba Lycopodii 45 parts and Scorpio 10 parts composition; Add the soak by water 2 times of Chinese medicine composition gross weight 10 times amount, and collect with volatile oil extractor and obtain volatile oil part, merge decocting liquid and obtain concentrate at 70 DEG C of concentrating under reduced pressure;
(2) get the concentrate that step (1) obtains and add ethanol, reflux, extract, 2 times, each 1 hour, merge ethanol extraction and concentrate, obtain ethanol concentrate;
(3) get macroporous adsorptive resins on ethanol concentrate that step (2) obtains, be the ethanol elution of 50% ~ 70% by volumetric concentration, merge 60% ethanol elution, concentrated, dry that extract be refined by ethanol;
(4) preparation of pastille hypothallus: get carboxymethyl cellulose 10 parts, polyvinyl alcohol 10 parts, adds 20 parts of water after mixing, leave standstill 24 hours, fully swelling, obtains gel A; Get polyvinyl alcohol 5 parts, add 15 parts of water, leave standstill 24 hours, dissolve in 95 DEG C of water-baths after fully swelling, obtain gel B.Mixed gel A and gel B in 70 DEG C of water-baths, be stirred to gel mix homogeneously, add 5 parts of polyglycereol, abundant stirring, add the ethanol that in step (1), gained volatile oil part and step (3) obtain afterwards and refine extract, be stirred to abundant mixing, finally add 2 parts of azones, 2 parts of propylene glycol, after abundant stirring and evenly mixing, namely obtain pastille hypothallus.
(3) the pastille hypothallus getting step (2) gained is coated on backing layer while hot, is covered with adherent layer after drying, cuts into suitable size, packs and get final product.
Embodiment 3
Have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, comprise backing layer, pastille hypothallus and adherent layer, its preparation method comprises the following steps:
(1) Radix Angelicae Sinensis 20 parts, Radix Codonopsis 15 parts is got, 15 parts, Flos Carthami, Radix Salviae Miltiorrhizae 15 parts, Rhizoma Chuanxiong 15 parts, Rhizoma Drynariae 10 parts, Rhizoma Cibotii 10 parts, Rhizoma Osmundae 6 parts, the Cortex Eucommiae 10 parts, Radix Dipsaci 10 parts, Rhizoma Corydalis 10 parts, Rhizoma Zingiberis 20 parts, Radix Angelicae Pubescentis 10 parts, Radix Dipsaci 10 parts, Radix Achyranthis Bidentatae 10 parts, the Radix Paeoniae Alba 5 parts, Caulis Sinomenii 6 parts, the Radix Astragali 20 parts, Semen Cuscutae 10 parts, Caulis Spatholobi 20 parts, Herba Pyrolae 10 parts, the Chinese medicine composition of Herba Lycopodii 15 parts and Scorpio 5 parts composition; Add the soak by water 3 times of Chinese medicine composition gross weight 8 times amount, and collect with volatile oil extractor and obtain volatile oil part, merge decocting liquid and obtain concentrate at 65 DEG C of concentrating under reduced pressure;
(2) get the concentrate that step (1) obtains and add ethanol, reflux, extract, 2 times, each 2 hours, merge ethanol extraction and concentrate, obtain ethanol concentrate;
(3) get macroporous adsorptive resins on ethanol concentrate that step (2) obtains, be the ethanol elution of 50% ~ 70% by volumetric concentration, merge 60% ethanol elution, concentrated, dry that extract be refined by ethanol;
(4) preparation of pastille hypothallus: get carboxymethyl cellulose 10 parts, polyvinyl alcohol 10 parts, adds 20 parts of water after mixing, leave standstill 24 hours, fully swelling, obtains gel A; Get polyvinyl alcohol 5 parts, add 15 parts of water, leave standstill 24 hours, dissolve in 95 DEG C of water-baths after fully swelling, obtain gel B.Mixed gel A and gel B in 70 DEG C of water-baths, be stirred to gel mix homogeneously, add 5 parts of polyglycereol, abundant stirring, add the ethanol that in step (1), gained volatile oil part and step (3) obtain afterwards and refine extract, be stirred to abundant mixing, finally add 2 parts of azones, 2 parts of menthols, after abundant stirring and evenly mixing, namely obtain pastille hypothallus.
(3) the pastille hypothallus getting step (2) gained is coated on backing layer while hot, is covered with adherent layer after drying, cuts into suitable size, packs and get final product.
Embodiment 4 blood circulation promoting and blood stasis dispelling is tested
1 experiment material
1.1 laboratory animal experiments use SD female rats, body weight 200g ± 10g, are provided by Heilongjiang University of Chinese Medicine's Experimental Animal Center (SPF level).
1.2 reagent hydrochloric acid epinephrine liquid, Tianjin Pharmaceutical Group Xinzheng Co., Ltd.; Sodium citrate, Tianjin Biochemical Pharmaceutical Factory produces.
1.3 instrument L G-R-80 computer Blood rheology measurements, Beijing Steellex Scientific Instrument Company's product.
2 experimental techniques
2.1 models are prepared normal group routine and are raised, and model group, treatment group (attaching the patch that the embodiment of the present invention 1 prepares) rat are placed in 0 DEG C ~ 1 DEG C frozen water 5min, every day 1 time, continuous seven days.Treatment group was in the 1st day of modeling, and the patch that patch inventive embodiments 1 prepares, is used in conjunction 7 days, and normal group, model group give the process of normal saline same method.In the 8th day subcutaneous injection 0.1% epinephrine 0.1ml/100g, totally 2 times, twice interval time 4h.Stop eating afterwards, Yu Cichen adopts full-automatic stream to accelerate and surveys instrument mensuration Hemorheology index; The method of radioimmunity is adopted to measure hormonal readiness in serum.
2.2 animals groupings select healthy cleaning grade SD female rats 50,3 months ages of Mus, body weight 200g ± 11g.After adaptability raises 1 week, 5 groups are divided into by random digits table, often organize 10, i.e. dosage group (1.0g/kg) and the heavy dose of group (3.0g/kg) of the embodiment of the present invention 1 patch in Normal group (normal group), model control group (model group), the embodiment of the present invention 1 patch low dose group (0.5g/kg), the embodiment of the present invention 1 patch.Normal group gives normal saline, and the large, medium and small dosage group of patch is applied to abdominal part unhairing place, continuous use 7 days.Copy cold blood stasis rat model as stated above.60min after last medication, carotid artery gets blood, measures hemorheology index.
3 experimental results and analysis
From table 1, compared with matched group, the whole blood viscosity of model group obviously raises (P<0.05), shows to adopt ice-water bath and Injection of Adrenaline to cause rat acute blood stasis model.Compared with model group, the height of the external use plaster that the embodiment of the present invention 1 prepares, middle dosage group all obviously reduce whole blood viscosity (P<0.01 or P<0.05) in high, medium and low rate of cutting.Patch low amounts group only suppresses whole blood viscosity to raise (P<0.05) in low rate of cutting, and shows effect of well invigorating blood circulation.
Table 1 Chinese medicine composition transdermal patch is on the impact of body blood reducing stasis model hemorheology of rat
Compared with model group, * P < 0.05; * P < 0.01
Shown by the experimental result shown above, Chinese medicine composition transdermal patch provided by the invention has good blood circulation promoting and blood stasis dispelling, increases skeleton blood volume amount, plays good promoting blood circulation to relieve pain effect.
Embodiment 5 mouse hot-plate induced pain is tested
1. experimental technique
ICR mice, 50, body weight 22 ~ 26 grams, is divided into blank group, transdermal patch low dose group (0.5g/kg) that the embodiment of the present invention 1 prepares, middle dosage group (1.0g/kg) and heavy dose of group (2.0g/kg) at random, often organizes 10.The analgesic effect of Chinese medicine composition transdermal patch is evaluated with hot plate stimulus method.Test front depilatory to lose hair or feathers at mouse web portion.Stick blank transdermal patch and Chinese medicine composition transdermal patch respectively at mouse web portion after 24 hours, blend compounds band paper is fixed, and prevents from coming off.Administration every day 1 time, continuous 2 days, after last administration 30 minutes, 1 hour, 2 hours, 4 hours, measures the threshold of pain time, compares group difference for 10 hours.
2. experimental result
Transdermal patch group stimulates the induced mice threshold of pain time to hot plate upon administration, and comparatively there is prolongation effect the administration front threshold of pain time, and still has obvious analgesic activity after 10 hours, compared with blank group, can significantly improve the mice threshold of pain time.Specific experiment result is as table 2.
The analgesic activity (n=10) that table 2 Chinese medicine composition transdermal patch is tested mouse hot-plate
Compare with before administration, * * P<0.01, * P<0.05; Compare with normal saline group, △ △ P<0.01, △ P<0.05.
Shown by the experimental result of above table 2, Chinese medicine composition transdermal patch provided by the invention has good analgesic activity, can significantly improve pain threshold, and the persistent period is longer, can play effect of continuous analgesia.
Embodiment 6 anti-inflammation test
1. experiment material
Instrument Drict-Q5 ultrapure water machine (Millipore); Rotary evaporator (instruments used for education company limited of Nanjing Nintaus); Electronic balance (Sartoris BP211D); Microscope (model OLMPUS CKX31); Microplate reader (model 680, BIO-RAD); Microplate reader (DENLEYDRAGONWellscan MK3, Thermo); Wash trigger (Wellwash4MK2, Thermo); Electronic balance (model JA2003N, Shanghai Precision Scientific Apparatus Co., Ltd); Centrifuge (Anke LXJ-IIB); Constant water bath box (Medical Instruments factory of HH-S Jintan City); Eddy mixer (XW-80A, Qingpu Shanghai Hu Xi instrument plant).
Reagent and sample F reund ' s Freund's complete adjuvant (100M8717CAS9007-81-2, sigma); Polyoxyethylene sorbitan monoleate (Shanghai Shen Yu medication chemistry company limited); Dehydrated alcohol (Wuxi City Ya Sheng Chemical Co., Ltd.); Rat IL-2ELISA test kit, P of Rats GE
2eLISA kit, rat TNF α ELISA kit (all purchased from Xi Tang bio tech ltd, Shanghai); Indomethacin (Shanghai Xin Pasi pharmaceutical Co. Ltd, lot number: H31020148); Pentobarbital sodium (German subpackage, lot number: WS20080810); Sodium citrate; Ultra-pure water is self-control; Sample is self-control.
Animal: cleaning grade SD rat.Rearing conditions: cleaning grade Animal Lab., room temperature 23-25 DEG C, relative humidity 40%-70%, suitable ventilation 15 times every day.
2. experimental technique
The foundation of 2.1 rat adjuvant type arthritis models
SD rat 72, male and female half and half, body weight, at 180-220g, is surveyed each Mus left and right metapedes sole of the foot volume, is separated 8 at random as blank group by weight, and all the other 64 are carried out modeling by literature method.Conventional method carries out disinfection to skin bottom the SD Rat Right metapedes sole of the foot, only carries out causing inflammation with microsyringe intradermal injection Freund ' s Freund's complete adjuvant 0.1mL/.After modeling the 13rd day, sufficient sole of the foot volume about measuring every rat, model group foot sole of the foot volume compared with blank group that there were significant differences, and observes and find that the sufficient sole of the foot red and swollen obviously prompting modeling is successful.
2.2 experiment groupings
Test be divided into blank group, model group, positive controls (Indomethacin, IMT), the embodiment of the present invention 2 to prepare at random by rat weight and foot swelling degree transdermal patch low dose group (0.5g/kg), middle dosage group (1.0g/kg) and heavy dose of group (2.0g/kg).
The observation of 2.3 rat general states and the evaluation of Articular swelling
Before modeling and administration fore-and-aft observing rat chaeta color and luster and activity situation, the increase change of appetite and redness and swelling of joints situation, and before modeling, after modeling after 13d, modeling after 20d, modeling after 24d, modeling after 27d, modeling 30d measure the body weight (g) of rat and the volume (mL) of the left and right sole of the foot.
Body weight: use electronic scale weighing rat body weight; Foot sole of the foot volume: the volume surveying the sole of the foot after about each group of rat with the sufficient sole of the foot measuring device of self-control, the change of each group rat paw edema degree after comparing administration.
The sampling and processing of 2.4 rat plasmas
With 10% chloral hydrate intraperitoneal injection of anesthesia rat, dorsal position is fixed, carotid artery gets blood, whole blood is collected in the centrifuge tube of 10mL with 3.8% sodium citrate (blood and anticoagulant volume ratio are 9:1) anticoagulant, with low speed centrifuge with the centrifugal 10min of 3000r/min rotating speed, Aspirate supernatant, stored frozen at-20 DEG C, detects MDA, PGE in blood plasma
2, IL-2.
The assay method of malonaldehyde (MDA)
Experiment measures the operational approach of test kit description according to malonaldehyde (MDA), measure the burst size of MDA.MDA test kit test philosophy: the malonaldehyde (MDA) in lipid peroxide catabolite can with thiobarbituricacidα-(TBA) condensation, form red product, have maximum absorption band at 532nm place.
By test kit, configuration reagent is described, gets above-mentioned gained serum, tissue supernatant, eight pipes got by each test sample, often pipe 50 μ L, eight pipes respectively got by blank tube and standard pipe, often pipe 50 μ L, often pipe adds mix reagent 1000 μ L respectively, with the mixing of vortex vortex mixer, test tube mouth preservative film is tightened, and stings an aperture with syringe needle, 95 DEG C of water-baths (or uncap with pot boil) 40 minutes, flowing water cooling after taking out, then 3500-4000r/min, centrifugal 10 minutes.Get supernatant 200 μ L in 96 orifice plates, 532nm place surveys the absorbance of each pipe, by following formulae discovery:
(1) computing formula of MDA content in serum:
(2) computing formula of NO content in tissue:
The assay method of interleukin-2 (IL-2), PGE2, TNF α
Experiment adopts double antibodies sandwich ABC-ELISA method, be coated in ELISA Plate with Chinese People's Anti-Japanese Military and Political College's Mus IL-2 monoclonal antibody, IL-2 in standard substance and sample is combined with monoclonal antibody, adds biotinylation and obtains Chinese People's Anti-Japanese Military and Political College Mus IL-2, forms immune complex and connects onboard, the streptavidin of horseradish peroxidase-labeled is combined with biotin, add substrate working solution aobvious blue, finally add stop buffer sulphuric acid, survey OD value at 450nm place, IL-2 concentration is directly proportional to OD value, is obtained the concentration of IL-2 in specimen by drawing standard curve.PGE
2, TNF
αthe Cleaning Principle of content is similar to the Cleaning Principle of IL-2.
By requirement configuration standard product, 10 × sample diluent, the cleaning mixture of test kit.Take out 96 hole ELISA Plate, every hole adds standard substance and testing sample 100 μ L successively, Sptting plate is fully mixed rearmounted 37 DEG C and hatches 120 minutes.With cleaning mixture, Sptting plate is fully washed 4-6 time, after print is done on filter paper, in every hole, add first antibody working solution 100 μ L, Sptting plate is fully mixed latter 37 DEG C and hatch 60 minutes, wash plate, after print is dry, every hole adds substrate working solution 100 μ L, Sptting plate is put dark place and reacts 15 minutes.Every hole adds the stop buffer mixing of 100 μ L again, surveys light absorption value in 30 minutes by microplate reader at 450nm place.
All OD values are gone after all should reducing blank value again and are calculated.With standard substance 2000,1000,500,250,125,62.5,31.2,0pg/mL for abscissa, OD value is vertical coordinate, and graph paper is mapped, and draws standard curve.OD value finds corresponding IL-2, PGE on the graph per sample
2, TNF
αcontent.
3 experimental results
3.1 cause scorching rear each change organizing rat different time body weight
Before administration, each group rat body weight and model group weight ratio are comparatively, normal group body weight and model group body weight have significant difference (P≤0.05), and all the other are group and the equal not statistically significant of model group comparing difference (P > 0.05) respectively.
3.2 cause scorching rear each impact organizing the right pedal swelling degree of rat different time
Cause scorching after the impact of the right pedal swelling degree of each group rat different time, table 3 is known, before modeling, normal group, administration group Rat Right foot sole of the foot volume all with model group there was no significant difference (P > 0.05); 13d after modeling, normal group compares with model group pole significant difference (P < 0.001), and all the other respectively organize the difference (P > 0.05) that to compare with model group that there are no significant; 20d after modeling, normal group, IMT group, medicine group compare with model group pole significant difference (P < 0.001), high, the middle dosage group of the transdermal patch that the embodiment of the present invention 2 prepares compares with model group significant differences (P < 0.01), and low dose group compares with model group significant difference (P < 0.05); 24d after modeling, high, the middle dosage group of the transdermal patch that the embodiment of the present invention 2 prepares compares with model group significant differences (P < 0.01), and all the other are respectively organized more all has significant difference (P < 0.01) with model group; After modeling, 27d, 30d respectively organize Rat Right foot sole of the foot volume and model group more even pole significant difference (P < 0.01), and transdermal patch provided by the invention shows effect of well subsiding a swelling.
The change of table 3 Rat Right pedal swelling degree
Note: compare with model group, * P < 0.05 indicates significant difference, and * * P < 0.01 indicates significant differences, and * * * P < 0.001 indicates pole significant difference.
3.3 on each impact organizing MDA, IL-2, PGE2 in rat plasma
As shown in Table 4, in normal rats blood plasma, MDA content compares with model group highly significant difference (P < 0.01), and the high, medium and low dosage group of the transdermal patch that the present invention prepares compares with model group highly significant difference (P < 0.01); IL-2, PGE in transdermal patch high, medium and low dosage group rat plasma
2level, more all has pole significant difference (P < 0.001) with model group.Result shows that the transdermal patch that the present invention prepares has MAD, IL-2, PGE in significant suppression adjuvant arthritis rats blood plasma
2level, has good antiphlogistic effects.
Table 4 is on the impact of MDA, IL-2, PGE2 content in rat plasma
Note: compare with model group, * P < 0.05 indicates significant difference, and * * P < 0.01 indicates significant differences, and * * * P < 0.001 indicates pole significant difference.
Embodiment 7 skin irritation test
1 material
1.1 animal health white rabbit, female, body weight (2.0 scholar 0.5) kg, is provided by Heilongjiang University of Chinese Medicine's Experimental Animal Center.
The Chinese medicine composition transdermal patch that 1.2 Medications Example 1 and embodiment 2 prepare
2 test methods
2.1 single administration Skin Irritation Test
Get healthy rabbits 8, be divided into 2 groups at random, often organize 4.24h before administration, be in 4, rabbit back both sides district's depilation 3cm × 3cm.Wherein before administration, on 4 depilation district skins, draw groined type with No. 9 syringe needles of sterilize for 1 group, all to damage horny layer, epidermis is hemorrhage is spend, as injured skin group.Another 1 group is intact skin group.Every rabbit skin of back divides 4th district: dosage district and transdermal patch high dose area in solvent control district, transdermal patch cold spot area, transdermal patch.Medicine is applied to respective regions respectively.Remove residual tested material with warm water after single administration 24h, to observe after removing tested material 1h, 24h, 48h and smear position 72h to week with or without the situation such as erythema and edema.
2.2 multiple dosing Skin Irritation Test test methods
With single administration Skin Irritation Test, after difference is 1 administration 24h, successive administration, continues 1 week.After 1 week, remove left drug, lh, 24h, 48h, 72h to 1 week observe with or without the situation such as erythema and edema, and the recovery situation of above-mentioned change and time.
3 results and analysis
3.1 single administration Skin Irritation Test
By observing, without edema phenomenon intact skin and each time point of damaged skin.After removing medicine 1h, there is slight erythema in the middle and high dosage group damaged skin of transdermal patch, integration is respectively 1.25 and 0.75, produces minimal irritation, non-stimulated to intact skin; Low dose group stimulates integration all lower than 0.5 to intact skin and damaged skin, nonirritant.Remove medicine after 1 day, each dosage group stimulates integration all lower than 0.5 to intact skin and damaged skin, nonirritant.After 7 days, 8 rabbit recover completely.
3.2 multiple dosing Skin Irritation Test
Through administration in continuous 7 days, transdermal patch high dose group had minimal irritation to damaged skin, and without edema, administration recovers normal on the 7th day afterwards.Middle dosage group has minimal irritation in 3 days before administration to damaged skin, and within 7 days, recover normal, other experimental group integrations are all less than 0.5, non-stimulated.
Shown by above experimental result, transdermal patch provided by the invention has good preventive and therapeutic action to constitutional prolapse of lumbar intervertebral disc, and in Clinical practice process, bioavailability is high, little to organ injury such as livers, little to skin irritation in use procedure, patient easily accepts, and can be developed into the external novel formulation into new anti-prolapse of lumbar intervertebral disc.
Above embodiment is only for illustrating technical conceive of the present invention and feature; its object is to allow person skilled in the art understand content of the present invention and to be implemented; can not limit the scope of the invention with this; all equivalences done according to spirit of the present invention change or modify, and all should be encompassed in protection scope of the present invention.
Claims (10)
1. one kind has the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, it is characterized in that, the adherent layer that it comprises backing layer, is fixed on the pastille hypothallus on backing layer and covers on pastille hypothallus, described pastille hypothallus comprises hydrogel matrix 15 ~ 45 parts, volatile oil part 15 ~ 45 parts, ethanol refine extract 30-90 part and transdermal penetration enhancer 8 ~ 24 parts;
Described volatile oil part is prepared by following method:
(1) Radix Angelicae Sinensis 20 ~ 40 parts is got, Radix Codonopsis 10 ~ 30 parts, 15 ~ 30 parts, Flos Carthami, Radix Salviae Miltiorrhizae 15 ~ 30 parts, Rhizoma Chuanxiong 15 ~ 30 parts, Rhizoma Drynariae 10 ~ 25 parts, Rhizoma Cibotii 5 ~ 20 parts, Rhizoma Osmundae 4 ~ 24 parts, the Cortex Eucommiae 10 ~ 30 parts, Radix Dipsaci 10 ~ 40 parts, Rhizoma Corydalis 10 ~ 40 parts, Rhizoma Zingiberis 20 ~ 40 parts, Radix Angelicae Pubescentis 10 ~ 30 parts, Radix Dipsaci 10 ~ 20 parts, Radix Achyranthis Bidentatae 10 ~ 40 parts, the Radix Paeoniae Alba 5 ~ 25 parts, Caulis Sinomenii 6 ~ 24 parts, the Radix Astragali 20 ~ 40 parts, Semen Cuscutae 10 ~ 20 parts, Caulis Spatholobi 20 ~ 40 parts, Herba Pyrolae 10 ~ 25 parts, the Chinese medicine composition of Herba Lycopodii 15 ~ 45 parts and Scorpio 5 ~ 10 parts composition, add the soak by water 2 ~ 3 times of Chinese medicine composition gross weight 8 ~ 15 times amount volume, and collect with volatile oil extractor and obtain volatile oil part, merge decocting liquid and obtain concentrate at 30 ~ 70 DEG C of concentrating under reduced pressure,
(2) get the concentrate that step (1) obtains and add ethanol, reflux, extract, 2 ~ 3 times, each 1 ~ 2 hour, merge ethanol extraction and concentrate, obtain ethanol concentrate;
(3) get macroporous adsorptive resins on ethanol concentrate that step (2) obtains, be the ethanol elution of 50% ~ 70% by volumetric concentration, merge 60% ethanol elution, concentrated, dry that extract be refined by ethanol.
2. according to claim 1 have the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, it is characterized in that, described Chinese medicine composition by Radix Angelicae Sinensis 40 parts, Radix Codonopsis 30 parts, 20 parts, Flos Carthami, Radix Salviae Miltiorrhizae 30 parts, Rhizoma Chuanxiong 25 parts, Rhizoma Drynariae 20 parts, Rhizoma Cibotii 10 parts, Rhizoma Osmundae 16 parts, the Cortex Eucommiae 20 parts, Radix Dipsaci 35 parts, Rhizoma Corydalis 20 parts, Rhizoma Zingiberis 40 parts, Radix Angelicae Pubescentis 16 parts, Radix Dipsaci 16 parts, Radix Achyranthis Bidentatae 30 parts, the Radix Paeoniae Alba 25 parts, Caulis Sinomenii 18 parts, the Radix Astragali 40 parts, Semen Cuscutae 20 parts, Caulis Spatholobi 30 parts, Herba Pyrolae 10 parts, Herba Lycopodii 20 parts and Scorpio 6 parts composition.
3. the transdermal patch with treatment prolapse of lumbar intervertebral disc according to claim 1 and 2, it is characterized in that, described hydrogel matrix comprises 5 ~ 20 parts of adhesive, 20 ~ 40 parts of framework materials and 10 ~ 30 parts of wetting agents.
4. the transdermal patch with treatment prolapse of lumbar intervertebral disc according to claim 3, it is characterized in that, described adhesive is sodium alginate or carboxymethyl cellulose.
5. the transdermal patch with treatment prolapse of lumbar intervertebral disc according to claim 4, it is characterized in that, described framework material comprises polyvinyl alcohol or PVP K30.
6. the transdermal patch with treatment prolapse of lumbar intervertebral disc according to claim 5, it is characterized in that, described wetting agent comprises glycerol or PEG400.
7. the transdermal patch with treatment prolapse of lumbar intervertebral disc according to claim 6, it is characterized in that, described transdermal penetration enhancer is one or more in azone, propylene glycol or menthol.
8. the preparation method with the transdermal patch preventing and treating prolapse of lumbar intervertebral disc according to claim 1, is characterized in that, comprise the following steps:
(1) Radix Angelicae Sinensis 20 ~ 40 parts is got, Radix Codonopsis 10 ~ 30 parts, 15 ~ 30 parts, Flos Carthami, Radix Salviae Miltiorrhizae 15 ~ 30 parts, Rhizoma Chuanxiong 15 ~ 30 parts, Rhizoma Drynariae 10 ~ 25 parts, Rhizoma Cibotii 5 ~ 20 parts, Rhizoma Osmundae 4 ~ 24 parts, the Cortex Eucommiae 10 ~ 30 parts, Radix Dipsaci 10 ~ 40 parts, Rhizoma Corydalis 10 ~ 40 parts, Rhizoma Zingiberis 20 ~ 40 parts, Radix Angelicae Pubescentis 10 ~ 30 parts, Radix Dipsaci 10 ~ 20 parts, Radix Achyranthis Bidentatae 10 ~ 40 parts, the Radix Paeoniae Alba 5 ~ 25 parts, Caulis Sinomenii 6 ~ 24 parts, the Radix Astragali 20 ~ 40 parts, Semen Cuscutae 10 ~ 20 parts, Caulis Spatholobi 20 ~ 40 parts, Herba Pyrolae 10 ~ 25 parts, the Chinese medicine composition of Herba Lycopodii 15 ~ 45 parts and Scorpio 5 ~ 10 parts composition, add the soak by water 2 ~ 3 times of Chinese medicine composition gross weight 8 ~ 15 times amount, and collect with volatile oil extractor and obtain volatile oil part, merge decocting liquid and obtain concentrate at 30 ~ 70 DEG C of concentrating under reduced pressure,
(2) get the concentrate that step (1) obtains and add ethanol, reflux, extract, 2 ~ 3 times, each 1 ~ 2 hour, merge ethanol extraction and concentrate, obtain ethanol concentrate;
(3) get macroporous adsorptive resins on ethanol concentrate that step (2) obtains, be the ethanol elution of 50% ~ 70% by volumetric concentration, merge 60% ethanol elution, concentrated, dry that extract be refined by ethanol;
(4) preparation of hydrogel matrix: get adhesive and framework material adds water, place 24 hours fully swelling, water-bath mix and add wetting agent, abundant stirring and evenly mixing, obtaining transparent sticky hydrogel matrix;
(5) step (1) volatile oil part 15 ~ 45 parts of parts are got and extract 30 ~ 90 parts refined by step (3) ethanol, be scattered in 15 ~ 45 parts of hydrogel matrixes that step (4) prepares, add transdermal penetration enhancer 8 ~ 24 parts, mix homogeneously, ultrasonic removing bubble, coat while hot on backing layer, after drying, be covered with adherent layer, to obtain final product.
9. preparation according to claim 8 has the method for the transdermal patch preventing and treating prolapse of lumbar intervertebral disc, it is characterized in that, the adhesive described in step (4) is sodium alginate or carboxymethyl cellulose; Described framework material is polyvinyl alcohol or PVP K30; Described wetting agent is glycerol or PEG400.
10. the preparation method with the transdermal patch preventing and treating prolapse of lumbar intervertebral disc according to claim 8, is characterized in that, the transdermal penetration enhancer described in step (5) is one or more in azone, propylene glycol or menthol.
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| CN107951981A (en) * | 2017-12-30 | 2018-04-24 | 黄旭东 | One analgesic bone hinders paint and preparation method thereof |
| CN108524556A (en) * | 2018-06-22 | 2018-09-14 | 何洁庄 | A kind of Chinese medicine composition and the preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101219197A (en) * | 2007-01-11 | 2008-07-16 | 李国盛 | Proprietary Chinese medicine for treating orthopedic disorders |
| CN102940754A (en) * | 2012-12-11 | 2013-02-27 | 南京中医药大学 | Rhizoma cyperi four-drug decoction transdermal patch and preparation method thereof |
| CN103736067A (en) * | 2014-01-20 | 2014-04-23 | 刘中元 | Traditional Chinese medicinal composition for treating protrusion of lumbar intervertebral disc |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101219197A (en) * | 2007-01-11 | 2008-07-16 | 李国盛 | Proprietary Chinese medicine for treating orthopedic disorders |
| CN102940754A (en) * | 2012-12-11 | 2013-02-27 | 南京中医药大学 | Rhizoma cyperi four-drug decoction transdermal patch and preparation method thereof |
| CN103736067A (en) * | 2014-01-20 | 2014-04-23 | 刘中元 | Traditional Chinese medicinal composition for treating protrusion of lumbar intervertebral disc |
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|---|---|---|---|---|
| CN107951981A (en) * | 2017-12-30 | 2018-04-24 | 黄旭东 | One analgesic bone hinders paint and preparation method thereof |
| CN108524556A (en) * | 2018-06-22 | 2018-09-14 | 何洁庄 | A kind of Chinese medicine composition and the preparation method and application thereof |
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