CN100482210C - External applied Chinese medicinal paste for treating arthralgia - Google Patents
External applied Chinese medicinal paste for treating arthralgia Download PDFInfo
- Publication number
- CN100482210C CN100482210C CNB2003101035476A CN200310103547A CN100482210C CN 100482210 C CN100482210 C CN 100482210C CN B2003101035476 A CNB2003101035476 A CN B2003101035476A CN 200310103547 A CN200310103547 A CN 200310103547A CN 100482210 C CN100482210 C CN 100482210C
- Authority
- CN
- China
- Prior art keywords
- chinese medicine
- plaster
- medicine composition
- methyl salicylate
- activity component
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 1
- 229960004555 rutoside Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- FWYIBGHGBOVPNL-UHFFFAOYSA-N scopoletin Natural products COC=1C=C2C=CC(OC2=C(C1)O)=O FWYIBGHGBOVPNL-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- ATKYNAZQGVYHIB-UHFFFAOYSA-N tropaic acid nortropanyl ester Natural products C1C(N2)CCC2CC1OC(=O)C(CO)C1=CC=CC=C1 ATKYNAZQGVYHIB-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Abstract
An exterior-applied Chinese medicine in the form of plaster for treating arthrodynia is prepared from fluid extract of hot pepper, fluid extract of belladonna, methyl salicylate, camphor, water-soluble matrix and carrier. Its advantage is high and durable curative effect.
Description
Technical field the present invention relates to a kind of Chinese medicine composition plaster of external curing arthralgia, more particularly, the present invention relates to a kind of Chinese medicine composition water solublity plaster of external curing arthralgia.Wherein, this medicine activity component is meant Fructus Capsici fluidextract, Semen daturae fluid extract, Oleum menthae, methyl salicylate, Camphora, iodine and potassium iodide, diphhydramine hydrochloride; Water-soluble base comprises binding agent, cross-linking agent, wetting agent, filler, surfactant etc., and this plaster is enhanced by water-soluble base to the transdermal penetration and the adhesion of health, belongs to the field of Chinese medicines.
Background technology is stated from Drug Standard of Ministry of Public Health of the Peoples Republic of China " the 3rd in Chinese traditional patent formulation preparation " as classical medicament one pain-relieving plaster for arthritis of treatment arthralgia at present, and its main component is Fructus Capsici fluidextract, Semen daturae fluid extract, Oleum menthae, methyl salicylate, Camphora, iodine and potassium iodide, diphhydramine hydrochloride.Wherein, the contained capsaicin of Fructus Capsici (Capsaicin) or claim the mainly release by influence the neuropeptide substance p on the C type sensory neuron of capsaicin, synthesize and preserved analgesia, itching-relieving action is widely used in the treatment of various superficial pain syndromes, intractable neuralgia, arthralgia and inflammation etc.; Semen daturae (herbabelladonnae) main component is the 1-hyoscyamine, account for 75～90% of total alkaloid content, other has a small amount of scopolamine, atropamine, atropina, norhyoscyamine, and contain what globulariacitrin of scopoletin etc., can ease pain, remove smooth muscle spasm, suppress glandular secretion etc. as anticholinergic agent; Mainly contain the 1-menthol in the Oleum menthae, account for 77～87%, the 1-menthone accounts for 10%, and the Herba Menthae esters accounts for 3～6%, is the fragrance medicine that dispels the wind, and that external has is antipruritic, the effect of pain relieving, refrigerant sense and counterirritation; Methyl salicylate is antiinflammatory, analgesic, and the part is used for joint or myalgia, has antiinflammatory, pain relieving, repercussive effect; Camphora (camphora) is the dextrorotation ketone compounds, and refrigerant sense is arranged, and can have one's ideas straightened out and ward off turbid, warming and odynolysis, is used for skin pruritus and inflammation outward; Iodine and potassium iodide are cosolvent; Diphhydramine hydrochloride is the derivant of ethanolamine, and antihistamine effect is arranged, can with the H on the histamine competitive effect cell that discharges in the tissue
1Receptor is prevented anaphylaxis thereby can resist or weaken histamine to the effect of blood vessel, gastrointestinal and bronchial smooth muscle, and external can be treated insect bite, neurodermatitis, pruritus etc.Pain-relieving plaster for arthritis is as the agent of a kind of external rubber patch, absorbs by transdermal penetration, can invigorate blood circulation, antiinflammatory, analgesia, and local vascular is had dilating effect, is used for the arthralgia that articular sprain and cold-damp cause.
Yet rubber-emplastrum need add Colophonium in process of production and make viscosifier, owing to himself easy oxidation, so the aged shortcoming of expedite product is arranged.Simultaneously, use big petrol aborning, not only environment is caused certain pollution, and rosin acid or residual gasoline easily causes stimulation to human body skin, cause red swelling of the skin and scratchy, skin allergy occurs; In addition,, tear-off pain and epilation phenomenon are arranged, easily cause physical property to pull and manifest many deficiencies human body skin because rubber-emplastrum viscosity is stronger.
In order to improve environment, reduce stimulation to skin, overcome many deficiencies of rubber-emplastrum, the water-soluble base plaster is early used in Japan.The Pharmacopoeia of the People's Republic of China one one of version in 2000 is defined as cataplasma with it, be meant medicinal substances extract, medicine and suitable hydrophilic matrix mixing after, be coated with and be laid on the external preparation of making on the cloth, English name is cataplasm, means plaster.At present, more and more many to the basic research of water-soluble base plaster both at home and abroad, for example 02112475.2,99103062.1,98102336.3 mainly is research to new type water-solubility substrate, does not relate to the application of concrete medicine, remains further exploitation.US6485740 (methotrexate), US6355266 (indomethacin) appear in the newspapers as the water soluble plaster treatment rheumatism of Western medicine, arthritic patent.Now, water soluble plaster is used more in Japanese Korea S, main carrying chemical drugs, nonsteroidal antiinflammatory drug for example, but this preparation is also rare in the application of the field of Chinese medicines, and for now, this type of tcm product of domestic industry production is also very rare, and is also fewer for the systematic study of this type of preparation.
By the test and document as can be known, be not that any one hydrophilic matrix all is fit to all medicines, in other words, in order to improve curative effect, make drug effect quick-acting, efficient, medicine must with specific water-soluble base compatibility, the i.e. different water-soluble base of different pharmaceutical coupling.
01127462.x in the domestic patent documentation, 00110089.0,94118339.4 02131281.8,02112476.0 Deng what introduce is the water soluble plaster of various concrete Chinese and western drugses, different with this patent principal agent composition, and aspects such as substrate composition and transdermal effect, clinical practice are not seen further investigation.The aqueous high molecular medicament layer of introductions such as ZL99251292.1 is made an issue of on the water-retaining property of water-soluble base mostly, the advantage of introduction many from low irritant, do not pull off the feather of etc. and to start with and not mentioned short saturating effect.The described band medicine of the external use plaster high-molecular gel layer that ZL99245346.1 introduces, thickness requires to be generally 0.2～4 millimeter according to the performance of medicine and treatment, does not state but see Table for the effect of hydrophilic in drug transdermal absorbs of the thickness of gel layer and high-molecular gel layer.
In transdermal research, prior art discloses a national natural science fund subsidy project (39970880): Zhu Quangang, the Hu Jinhong of Changhai hospital pharmacy portion of The 2nd Army Medical College is based upon body pig ear vein perfusion percutaneous absorbing model, the employing method is to choose one section in the young pig of firm wean ear edge vein, intubate, set up by artificial gas, sample room, constant flow pump, constant temperature system, politef connection tube, pig ear vein, pig ear skin and special laminar flow equipment etc. form in body pig ear vein perfusion percutaneous absorbing model.Detect the biologic activity of evaluation model with glucose utilization test and lactic acid dehydrogenase activity, with the methyl salicylate is model drug, 6.6% methyl salicylate gel, 2 grams are spread upon on the area 2cm*3cm, with high effective liquid chromatography for measuring methyl salicylate and the salicylic content of metabolite thereof.The result shows: part is metabolised to salicylic acid in the methyl salicylate transdermal penetration process, and methyl salicylate accumulation infiltration capacity Q and the regressive equation of time t are Q=-3.8090+6.1290t during stable state, and steady-state permeation speed is 6.1290 μ gcm
-2H
-1, plaster of the present invention by comparison, infiltration rate is its 2～5 times, the accumulation transdermal penetration amount of methyl salicylate〉300g/cm
2. day, the accumulation transit dose significantly improves, and is far superior to the drug delivery system of prior art.
Summary of the invention Chinese medicine composition plaster of the present invention is made up of medicine activity component, water-soluble base and carrier.Carrier is meant backing and isolating membrane.
As the water soluble plaster of external preparation for skin, the speed of drug release and absorption has speed with the different of substrate, and the affine degree of medicine in hypothallus is very big to the drug effect influence.One: must possess good preparation stability, this needs medicine and substrate that stronger affinity is arranged; Its two, the affinity of medicine and substrate size directly influences the Transdermal absorption effect of medicine.Usually substrate is low more to the affinity of medicine, helps the release and the absorption of medicine more.The present invention uses Fructus Capsici fluidextract, Semen daturae fluid extract, Oleum menthae, methyl salicylate, Camphora, iodine and potassium iodide, diphhydramine hydrochloride as medicine activity component, because the existence of a large amount of oiliness medicines, how to make itself and water-soluble base stablize coexistence, and medicine can comparatively fast be discharged from substrate, giving full play to drug effect, is a great problem that the present invention faces.
The present invention has screened a large amount of matrix formulations by a series of tests, has finally solved this difficult problem, and obtains beyond thought effect.
The present invention's employing has chance easy swelling of water and remollescent polyacrylate and bivalence and makes the water soluble polymer skeleton to the network structure that the tetravalent metal compound crosslink forms, add propylene glycol, glycerol, sorbitol, polyvinyl alcohol and polyvinylpyrrolidone (PVP) as wetting agent, the compositions of polyacrylate and Resina persicae and/or arabic gum is a binding agent, montorillonite clay, Kaolin, titanium dioxide and compositions thereof are the water-soluble base that filler constitutes, and have given full play to the pharmacological action of medicine activity component.Both solved the galenic pharmacy stable problem of medicine activity component in substrate, make the suitable partition coefficient of medicine tool between substrate/skin layer again, make medicine activity component from substrate, to discharge very soon, see through skin, thereby arrive focus rapidly, performance curative effect, so that the accumulation transdermal penetration amount of the active component of percutaneous dosing (with methyl salicylate as the transdermal identification of medications)〉300 μ g/cm
2. day, compared with prior art produced significant difference, make the percutaneous dosing of this Chinese medicine composition reach the marked improvement of ahead of estimate, be far superior to the drug delivery system of prior art.
This paper is described below in more detail to the present invention: plaster of the present invention is made up of three-decker
(i) backing layer: backing can be the blended cloth or the non-woven fabrics of all cotton fabric, chemical fiber cloth, cotton and chemical fibre
(ii) medicated layer: the water-soluble base layer that promptly contains the medicine active component
(iii) isolating membrane: i.e. the peel ply material that should throw off before being attached on the skin of one deck can be nontoxic polyethylene or polypropylene film, silicone oil paper
This Chinese medicine composition plaster is characterized in that: this plaster Chinese medicine active component is enhanced by water-soluble base to the transdermal penetration and the adhesion of health.
Water-soluble base in the medicated layer mainly is to be made of binding agent, wetting agent, filler, cross-linking agent, pH regulator agent, surfactant and water, each amounts of components is: adhesive ingredients comprises polyacrylic acid and salt, Resina persicae, arabic gum, sodium alginate, hydroxypropyl methylcellulose (HPMC) and compositions thereof, the compositions of optimization polypropylene hydrochlorate and Resina persicae and/or arabic gum, it accounts for 1～20 part in whole substrate.Gained plaster tack of the present invention is checked according to bead laboratory method under 2000 editions cataplasma items of the Pharmacopoeia of the People's Republic of China, 12～No. 26 better, if be lower than bead No. 12, just there is not suitable epidermis adhesiveness, firm inadequately to the stickup of joint part, easily come off, be higher than No. 26, the skin pain of can slightly pulling off the feather of preferred 16～No. 22, can reach 5～7 days to the attaching at body joints position; 0.5～20 part of filler can be selected from Kaolin, montorillonite clay, titanium dioxide (TiO
2), calcium carbonate, zinc oxide, kieselguhr, bentonite etc., preferred Kaolin, montorillonite clay and titanium dioxide (TiO
2) and combination.Be lower than 0.5 part of no obvious reinforcing effect, be higher than 20 parts, product loses viscoelasticity; 10～45 parts of wetting agents are made up of glycerol, propylene glycol, sorbitol, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), are higher than 45 parts, can cause the skin surface greasy feeling or be pasted with coolness, are lower than 10 parts, and product can't keep enough moisture; 0.1～5 part of cross-linking agent comprises that bivalence arrives the tetravalent metal chemical compound, as: aluminum sulfate, aluminium hydroxide AL (OH)
3, U-Ramin MC, tri-chlorination lead, four zinc chloride etc.; 0.05～2 part of pH regulator agent comprises tartaric acid; 0.1～5 part in surfactant is as tween 80 (Tween-80), hydrogenated castor wet goods; The scope of moisture is 25～85 parts, and when water content during greater than 85 parts, the gained mastic easily oozes cloth, leaks cream, and is when water content less than 20 parts time the, gained mastic viscosity height, mobile poor.
Medicine activity component content range in the medicated layer is Fructus Capsici fluidextract 0.5～85%, Semen daturae fluid extract 0.5～85%, Oleum menthae 0.25～10%, methyl salicylate 0.25～30%, Camphora 0.25～35%, iodine (I
2) 0.25～5%, potassium iodide (KI) 0.25～5%, diphhydramine hydrochloride 0.01～5%; Be preferably Fructus Capsici fluidextract 10～45%, Semen daturae fluid extract 10～45%, Oleum menthae 0.5～8%, methyl salicylate 5～20%, Camphora 10～45%, iodine 0.5～5%, potassium iodide 0.5～5%, diphhydramine hydrochloride 0.01～3%.
The present invention adopts the three therapeutic methods of traditional Chinese medicine in an appendix XD of Pharmacopoeia of the People's Republic of China version in 2000 the drug release determination method, release medium is 30% ethanol normal saline solution, investigated each active component release conditions of medicine with method, the result shows that the release of each active component is proportionate, therefore select for use wherein play main pharmacodynamics and detect accurately, methyl salicylate is as the identification of medications of transdermal experiment of the present invention easily.
Illustrate the present invention in more detail by following embodiment, but the invention is not restricted to these embodiment.
Produced the Chinese medicine composition plaster by following method.
Preparation technology:
1, oil phase A: medicine activity component and surfactant are at 70 ℃ mixture;
2, aqueous phase B: polyvinyl alcohol, polyvinylpyrrolidone, Resina persicae, sorbitol heat mixture soluble in water together;
3, solid phase is disperseed C: filler such as Kaolin and pH regulator agent, cross-linking agent, polyacrylic acid or its salt and glycerol, propylene glycol are uniformly dispersed.
In 80 ℃ aqueous phase B is added among the oil phase A gradually, stir fast and carry out emulsifying, then emulsive mixture is added solid phase and disperse C, stir 2 hours promptly.
Even mastic is applied on the non-woven fabrics, drying, overlay film promptly gets water solublity Chinese medicine composition plaster.
Table 1
Annotate 1: tack adopts Pharmacopoeia of the People's Republic of China version appendix in 2000 II[adhesion test] the bead method
Annotate 2: surface smoothness standards of grading: (preparation stability investigation index)
Excellent: any surface finish is indefectible
Very: bubble is arranged, flaw or particulate matter but every 50cm
2Total quantity is no more than one
In: bubble is arranged, the every 50cm of flaw or particulate matter
2Total quantity is above one
Difference: bubble is arranged, the every 50cm of flaw or particulate matter
2Total quantity is above five
Annotate 3: cohesive strength standards of grading: (preparation stability investigation index)
Excellent: as to stick to surpass 24 hours and do not produce and take off cream or distortion and residual phenomena
Very: pasting not produce in 24 hours and taking off cream or distortion and residual phenomena
In: pasting back little residual phenomena that has in 24 hours
Difference: pasting back a large amount of residual phenomena in 24 hours
Annotate 4: hold the viscosity standards of grading: after 10 healthy man's ancons were pasting in 12 hours, check.
Excellent: nothing comes off or peels off phenomenon
Very: have part edge phenomenon to occur peeling off, but none comes off
In: the part plaster occurs coming off but is no more than 2
Difference: come off above two
Annotate 5: the power of casting anchor standards of grading: after 10 healthy man's ancons were pasting in 12 hours, check.
(preparation stability investigation index)
Excellent: as not have mastic and backing segregation phenomenon when peeling off
Very: occur a routine mastic and ground edge separation phenomenon when peeling off
In: many cases mastic and ground edge separation phenomenon appear when peeling off
Difference: occur the complete segregation phenomenon of mastic and backing when peeling off
By table 1 as can be known, not all water-soluble base can both play potentiation to the drug effect of medicine activity component, and different water-soluble base prescriptions is different to the transdermal influence of medicine.Simultaneously, " pharmacological experimental methodology " (the 3rd edition) (Beijing: People's Health Publisher with reference to chief editors such as Xu Shuyun, 2002:234-235,237.) and Sheng Guorong etc. about the antipruritic emulsifiable paste animal experiment study of antiallergic (Strait Pharmaceutical Journal 2000, (1) 12:30-31.) carries out the drug safety experiment, by animal skin zest and anaphylaxis experiment, we have investigated the medicine activity component weight range that unit are substrate can be carried.Embodiment 9-13 (seeing Table 2)
Table 2
Annotate: each active component content of medicine is a Fructus Capsici fluidextract 28.7%, Semen daturae fluid extract 17.2%, Oleum menthae 5.74%, methyl salicylate 11.47%, Camphora 28.7%, iodine 4.02%, potassium iodide 2.3%, diphhydramine hydrochloride 1.87%.
Above-mentioned experiment: mix five kinds of plaster of the different drug loading of gained unit are with containing the not commensurability medicine activity component of 0.5g, 1.5g, 2.5g, 3.5g, 5.0g respectively successively with equivalent substrate.Experimental results show that through animal skin zest and anaphylaxis, the weight percentage ranges that this plaster contains the medicine active component is 0.8～7.0% o'clock, have the advantages of good skin safety,, will cause certain skin irritation if continue to improve the content of medicine activity component in substrate.
Hence one can see that, it is medicine activity component that Chinese medicine composition plaster of the present invention is used Fructus Capsici fluidextract, Semen daturae fluid extract, Oleum menthae, methyl salicylate, Camphora, iodine and potassium iodide, diphhydramine hydrochloride, water-soluble base combination with tool good comfort, drug compatibility, the gained plaster has that cohesiveness is good, moisture retention is good, attaching is comfortable, the unit are drug loading is big, in the effective range after no sensitization, zest, the use tear-off do not have pain, show good pharmaceutical preparation advantage.
Chinese medicine composition plaster of the present invention shows tangible medicine reinforced effects in in-vitro percutaneous permeability experiment, even do not add under the situation of any penetration enhancer, still obtained good transdermal effect, improved the infiltration capacity of medicine activity component more significantly than prior art, and, after adding penetration enhancer, transit dose is multiplied.See embodiment 14-17.
The medicated layer prescription:
2.5 parts of 1.5 parts of Resina persicaes of 3 parts of PVP0.5 parts of PVA sorbitol
2 parts of 5 parts of propylene glycol of 0.5 part of glycerol of 1.5 parts of Kaolin of sodium polyacrylate
2 parts of 0.2 part of medicines of 0.5 part of tartaric acid of 1.5 parts of tween 80s of aluminium hydroxide
40.5 parts of penetration enhancer of water
Embodiment 14: medicated layer prescription+2.5% azone
Embodiment 15: medicated layer prescription+4% ethanol
Embodiment 16: medicated layer prescription+3%N-methyl pyrrolidone
Embodiment 17: medicated layer prescription+4% ethyl acetate
The in-vitro percutaneous permeability experiment of being carried out among the present invention is as follows:
Franz diffusion cell method: the little Corium Mus of the processing of learning from else's experience is fixed in sample cell and accepts between the pond, is affixed on mice cornu cutaneum matter aspect with not containing penetration enhancer respectively with the plaster that contains different penetration enhancer, and acceptable solution is 30% ethanol normal saline solution, the fixed sample pond.Constant temperature (32 ± 0.5) ℃, respectively at sampling in 2,4,6,8,10,12,16,24 hours, each sampling amount is 0.5ml, and the fresh reception liquid of additional equal-volume, adopt the HPLC method to measure the drug level that receives methyl salicylate in the liquid, thereby the accumulation transmitance of the Chinese medicine of respectively writing out a prescription, (GUANJIE ZHITONG XIANGJIAO GAO and methyl salicylate gel experimental technique are the same) result shows as table:
Table 3
Annotate: methyl salicylate gel adopts the preparation method of methyl salicylate gel in body pig ear vein perfusion percutaneous absorbing model:
Carbomer-9401.0g is added in an amount of distilled water, treat to add after its complete swelling triethanolamine and make gel-type vehicle in right amount; In addition methyl salicylate 6.6g is dissolved in an amount of dehydrated alcohol, the continuous stirring adds down in the gel-type vehicle, continues adding distil water to 100g, stirs well and spares promptly.
This experiment conclusion shows: compare with GUANJIE ZHITONG XIANGJIAO GAO, the onset of Chinese medicine composition plaster is more rapid, local drug concentration is higher, its curative effect superior articular pain relieving rubber cream; Compare with methyl salicylate gel, though the gel onset is fast slightly, infiltration rate is lower, and drug effect is not remarkable, and uses inconvenience, easily pollution clothes.Hence one can see that, and Chinese medicine composition plaster of the present invention adopts described specific water soluble substrate, not only promotes drug transdermal to absorb, and existing preparations such as the remarkable superior articular pain relieving of transdermal effect rubber cream and gel.
Embodiment 18: clinical drug effect evaluation
For evaluating Chinese medicine composition plaster of the present invention and rubber cream, gel in the difference aspect the curative effect, we have carried out clinical observation to 36 routine arthralgia volunteers, now the result is reported as follows: selected volunteer's age is 18 years old～65 years old, do not have the other factors that influences drug evaluation and (comprise blood, liver, cardiovascular disease or other pathological changes, do not accept other drug such as analgesic, NSAID (non-steroidal anti-inflammatory drug) and muscle relaxant treatment and naturopathy simultaneously), clear and definite arthralgia is arranged, the patient that should understand to some extent clinical verification.Adopt at random, comparative study, the treatment group is the Chinese medicine composition plaster, the treatment medicine press embodiment 4 and is prepared; Matched group 1 is GUANJIE ZHITONG XIANGJIAO GAO (a commercial commercially available product); Matched group 2 is methyl salicylate gel (self-control, method is the same).Usage is and sticks in the articular surface of getting involved, and is for 1 week the course of treatment.By patient oneself write down first onset time (minute) and arthralgic diary every day (before sleeping every night, carry out on VAS100mm method, that night after medication, write down altogether 7 days).
Different time sections onset crowd percent after table 4 first administration
| Onset time (minute) | 30 | 60 | 120 | 180 | 240 |
| Chinese medicine composition plaster group (%) | 43.28 | 62.69 | 73.13 | 76.12 | 80.60 |
| Rubber cream group (%) | 35.38 | 50.77 | 56.92 | 63.08 | 64.62 |
| Methyl salicylate gel (%) | 56.81 | 64.25 | 66.27 | 68.09 | 71.22 |
After treatment, two groups of patients all have clear improvement to patient's articular pain and activity evaluation bitterly to arthralgic assessment and doctor, utmost point significant difference (P＜0.001) is more all arranged, Chinese medicine composition plaster group superior articular pain relieving as a result rubber cream group, methyl salicylate gel group before treating with after treating.Three groups the total effective rate toatl proportion of produce effects (effectively and) is respectively 89.10%, 71.6%, 76.92%, and the general curative effect superior articular pain relieving rubber cream and the methyl salicylate gel of Chinese medicine composition plaster is described.
Observe proof by above animal transdermal experiment and volunteer's medication: the described Chinese medicine composition plaster of patent of the present invention obviously is better than existing preparation on onset time, curative effect of medication, has greatly improved the transdermal efficient of external transdermal drug-supplying system, strengthens drug effect.
Claims (9)
1. the Chinese medicine composition plaster of an external curing arthralgia, this plaster is made up of medicine activity component and water-soluble base and carrier, it is characterized in that, account for 0.8～7.0% by weight medicine activity component, specific water-soluble base accounts for 93.0～99.2%, and is the pH regulator agent with tartaric acid; This medicine activity component is Fructus Capsici fluidextract 0.5～85%, Semen daturae fluid extract 0.5～85%, Oleum menthae 0.25～10%, methyl salicylate 0.25～30%, Camphora 0.25～35%, iodine 0.25～5%, potassium iodide 0.25～5%, diphhydramine hydrochloride 0.01～5% by weight; In the specific water-soluble base, it consists of 1～20 part of binding agent, 10～45 parts of wetting agents, 0.5～20 part of filler, 0.1～5 part in surfactant, 0.1～5 part of cross-linking agent, 0.05～2 part of pH regulator agent, 25～85 parts in water.
2. the Chinese medicine composition plaster of the described external curing arthralgia of claim 1, its carrier is meant backing and isolating membrane, this backing is the blended cloth or the non-woven fabrics of all cotton fabric, chemical fiber cloth, cotton and chemical fibre, and isolating membrane is silicone oil paper, nontoxic polyethylene or polypropylene film.
3. the Chinese medicine composition plaster of the described external curing arthralgia of claim 1, its each medicine activity component by weight, content range is as follows:
Fructus Capsici fluidextract 10～45% Semen daturae fluid extracts 10～45% Oleum menthae 0.5～8%
Methyl salicylate 5～20% Camphoras 10～45% iodine 0.5～5%
Potassium iodide 0.5～5% diphhydramine hydrochloride 0.01～3%
4. the Chinese medicine composition plaster of the described external curing arthralgia of claim 3, its each medicine activity component by weight, content range is as follows:
Fructus Capsici fluidextract 28.7% Semen daturae fluid extract 17.2% Oleum menthae 5.74%
Methyl salicylate 11.47% Camphora 28.7% iodine 4.02%
Potassium iodide 2.3% diphhydramine hydrochloride 1.87%
5. the described Chinese medicine composition plaster of claim 1, its binding agent are selected from one or more the combination in polyacrylate, Resina persicae, the arabic gum.
6. the described Chinese medicine composition plaster of claim 1, its wetting agent is made up of glycerol, propylene glycol, sorbitol, polyvinyl alcohol and polyvinylpyrrolidone.
7. the described Chinese medicine composition plaster of claim 1, its filler is selected from Kaolin, montorillonite clay, titanium dioxide (TiO
2), the combination of a kind of or Kaolin and titanium dioxide in the calcium carbonate, zinc oxide, kieselguhr, bentonite.
8. the described Chinese medicine composition plaster of claim 1, the cross-linking agent in its specific water soluble substrate is an aluminium hydroxide.
9. the described Chinese medicine composition plaster of claim 1, its specific water soluble substrate also can include penetration enhancer, and this penetration enhancer comprises azone, N-Methyl pyrrolidone, ethanol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2003101035476A CN100482210C (en) | 2003-11-07 | 2003-11-07 | External applied Chinese medicinal paste for treating arthralgia |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2003101035476A CN100482210C (en) | 2003-11-07 | 2003-11-07 | External applied Chinese medicinal paste for treating arthralgia |
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| Publication Number | Publication Date |
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| CN1613463A CN1613463A (en) | 2005-05-11 |
| CN100482210C true CN100482210C (en) | 2009-04-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB2003101035476A Expired - Fee Related CN100482210C (en) | 2003-11-07 | 2003-11-07 | External applied Chinese medicinal paste for treating arthralgia |
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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101879250B (en) * | 2010-06-25 | 2012-10-31 | 安舒贴(天津)外用制剂科技有限公司 | Arthralgia relief gel paste and preparation method |
| CN103893727B (en) * | 2014-03-30 | 2016-08-10 | 禹骏 | A kind of relieving pain and activating blood circulation relaxing muscles and tendons plaster and preparation method thereof |
| CA3057129C (en) * | 2014-06-16 | 2021-07-20 | Unigen, Inc. | Compositions and methods for managing or improving bone disorders, cartilage disorders, or both |
| CN105030900A (en) * | 2015-07-08 | 2015-11-11 | 吴秉民 | Externally used paste for treating rheumatic and rheumatoid arthritis and its preparation method and use |
| CN107296951A (en) * | 2017-07-28 | 2017-10-27 | 四川利佰生物科技有限公司 | Rheumatism cold compress patch and preparation method thereof |
| CN107375528A (en) * | 2017-08-10 | 2017-11-24 | 杭州仁德医药有限公司 | A kind of analgesic rheumatoid plaster and preparation method thereof |
| CN107432895B (en) * | 2017-08-17 | 2021-05-25 | 杭州仁德医药有限公司 | External plaster for eliminating dampness and relieving pain |
| CN114652708B (en) * | 2022-03-07 | 2024-04-26 | 宁波奇致年华医疗科技有限公司 | Composition for treating deep tissue pain |
-
2003
- 2003-11-07 CN CNB2003101035476A patent/CN100482210C/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| 中药成方制剂 第三册. 79. 1991 |
| 中药成方制剂 第三册. 79. 1991 * |
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| CN1613463A (en) | 2005-05-11 |
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Address after: Room 101, unit 2, building MoMA 5, yard 1, anningzhuang West Road, Haidian District, Beijing 100085 Patentee after: BEIJING ORIENTKING PHARMACEUTICAL SCIENCE & TECHNOLOGY Co.,Ltd. Address before: Room 2116, 2 floors, 3 Zhongke Industrial Park, 103 Beiqing Road, Haidian District, Beijing, 100094 Patentee before: BEIJING ORIENTKING PHARMACEUTICAL SCIENCE & TECHNOLOGY Co.,Ltd. |
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