CN101879147B - Lornoxicam hydrogel patch and preparation method thereof - Google Patents
Lornoxicam hydrogel patch and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a lornoxicam hydrogel patch and a preparation method thereof. In the hydrogel patch, lornoxicam is used as a medicinal active ingredient, and the hydrogel patch consists of a medicament-containing matrix, an adhesive layer, a lining layer and a protective layer, wherein the medicament-containing matrix consists of the lornoxicam, a hydrogel matrix and a penetrating agent. The patch makes the medicament release stably to prolong half-life period, is remarkably superior to other conventional preparations of the lornoxicam, and has the 48-hour accumulated permeation quantity of over 300ug.cm<-2> through percutaneous experiments in vitro. Pharmacodynamic tests prove that the lornoxicam hydrogel patch has excellent effect of relieving pain and diminishing inflammation.
Description
Technical field
The present invention relates to a kind of Lornoxicam hydrogel patch and preparation method thereof.
Background technology
Lornoxicam (commodity are by name can fill in wind) is a kind of NSAID (non-steroidal anti-inflammatory drug) of Nycomed company research and development, belongs to the thiazide derivant, has stronger analgesia and antiinflammatory action.This medicine has been widely used in the rear acute pain of operation clinically, also can be used for the treatment of chronic back pain, osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.Now by the first ladder medicine recommendation of WHO as the control cancer pain.Yet the use of ability of most NSAIDs is subject to the restriction of the restriction of associated side effect, particularly gastrointestinal side effect.Studies show that, the rate of adverse reactions of using due to the lornoxicam injection is about 10%, clinical manifestation mainly be feel sick, the gastrointestinal reactions such as vomiting, stomachache, diarrhoea.
Percutaneous drug administration preparation is compared to oral and the intramuscular injection dosage form, and it can avoid the contingent liver first-pass effect of oral administration and the intestines and stomach deactivation, has improved therapeutic effect, reduces toxicity.Controlled pharmacy enters human circulation near constant release, gives full play to the therapeutical effect of medicine, absorbs relatively steadily, has avoided the repeatedly blood medicine peak valley undulatory property that occurs of medication of other preparation.Prolong action time, reduce administration number of times.The patient can free medication, and is convenient.Publication number is that the Chinese patent of CN1927191A discloses a kind of lornoxicam transdermal administration plaster.But it is substrate that this patent adopts fat-soluble pressure sensitive adhesive, and drug releasing rate is slower, can not fully meet clinical needs.
Hydrogel patch is a kind of novel transdermal administration dosage form, compares with traditional patch, has distinctive advantage: (1) it and water solublity, fat-soluble medicine intermiscibility are good, and the substrate drug loading is large, are fit to very much Chinese medicine multicomponent, heavy dose of medication characteristics; (2) the hydrophilic hydrogel patch usually contains and surpasses 50% moisture, easily makes keratodermatitis softening, is conducive to the Transdermal absorption of medicine; (3) hydrophilic hydrogel patch breathability, skin adherence, heat insulating ability all are better than traditional patch, thereby have use comfortable, little to skin irritation, can repeatedly take off and paste and stick, do not take off after pollution clothes, noresidue, the use and paste without advantages such as pains.
Summary of the invention
The purpose of this invention is to provide a kind of Lornoxicam hydrogel transdermal patch and preparation method thereof.It has changed the route of administration of lornoxicam, in conjunction with the advantage of hydrogel, has both remedied and has had the deficiency that dosage form exists now, overcomes again the shortcomings such as the traditional patch release is slow, chance water loses viscosity, the easy allergy of life-time service.
Lornoxicam hydrogel patch provided by the present invention, take lornoxicam as active constituents of medicine, it is comprised of pastille substrate, adhered layer, backing layer and protective layer; Wherein, described pastille substrate comprises lornoxicam, hydrogel matrix and penetrating agent.
The mass ratio of lornoxicam and hydrogel matrix can be 1 in the described pastille substrate: 80-500, preferred 1: 100-320; The quality of described penetrating agent can be the 10-20% of hydrogel matrix quality.
Every square centimeter of lornoxicam 0.1～10mg of described Lornoxicam hydrogel patch, preferred 0.1-1mg.
Wherein, described hydrogel matrix can be by following 1)-3) material of arbitrary described quality percentage composition forms:
1) 5-20% hydrophilic polymer framework material, 10-30% wetting agent and 50-70% deionized water;
2) 5-20% hydrophilic polymer framework material, 10-30% wetting agent, 0-0.3% cross-linking agent and 50-70% deionized water; Wherein, the content of cross-linking agent is not 0;
3) 5-20% hydrophilic polymer framework material, 10-30% wetting agent, 0-0.3% cross-linking agent, 0-0.3% cross-linking regulator and 50-70% deionized water; Wherein, the content of cross-linking agent and cross-linking regulator all is not 0.
According to selected hydrophilic polymer framework material, select the different hydrogel matrixes that form.
Described hydrogel matrix is preferably by following 4)-6) in the material of arbitrary described quality percentage composition form:
4) 10-20% hydrophilic polymer framework material, 10-20% wetting agent and 60-70% deionized water;
5) 10-20% hydrophilic polymer framework material, 10-20% wetting agent, 0.08-0.3% cross-linking agent and 60-70% deionized water;
6) 10-20% hydrophilic polymer framework material, 10-20% wetting agent, 0.08-0.3% cross-linking agent, 0.12-0.3% cross-linking regulator and 60-70% deionized water.
Described penetrating agent is selected from one or more the combination in the penetrating agents such as sulfoxide type, pyrrolones, azone and analog thereof, fatty acid and ester thereof, surfactant, alcohols, polyalcohols, terpenes, amine, amide-type, cyclodextrin, aminoacid and ester thereof, macrocyclic compound, organic solvent class, phospholipid; Such as ethanol, propylene glycol, azone, oleic acid, lauryl alcohol, menthol, myristic acid isopropyl ester, hydroxypropyl cyclodextrin, Polyethylene Glycol (PEG400) etc.
Described hydrophilic polymer framework material specifically can be selected from following at least a: be polyvinylpyrrolidone, polyvinyl alcohol, sodium polyacrylate, polyacrylamide, carbomer, hydroxyethyl-cellulose, hydroxypropyl cellulose, hypromellose, carboxymethyl cellulose, sodium carboxymethyl cellulose and sodium alginate.
Described wetting agent can be selected from following at least a: glycerol, Polyethylene Glycol, sorbitol, propylene glycol and butanediol;
Described cross-linking agent can be selected from following at least a: aluminium hydroxide, calcium hydroxide, hydroxy Al, aluminum chloride and calcium chloride.
Described cross-linking regulator can be selected from following at least a: tartaric acid, citric acid, lactic acid and hydroxyl succinic acid.
Described pastille substrate also can comprise a certain amount of organic solvent (such as dimethyl formamide).
Certain described pastille substrate can only be comprised of lornoxicam, hydrogel matrix and penetrating agent; Or formed by lornoxicam, hydrogel matrix, penetrating agent and organic solvent.
Described adhered layer is that pressure sensitive adhesive forms, and does not contain medicine or contains some drugs as loading dose.The selection of material be Polyisobutylene PSA, silicone pressure-sensitive adhesive, acrylate pressure sensitive adhesive polyacrylate pressure-sensitive or natural rubber.
Described backing layer is made by following any one material: clad aluminum foil, polyethylene, polrvinyl chloride, polypropylene, polystyrene, polyester, poly-to this dioctyl phthalate second diester and non-woven fabrics.
Described protective layer is polyethylene, polystyrene, polypropylene, Merlon, separate paper or the fluorine material of processing through paraffin or Organosilicon Release Agent.
The method for preparing Lornoxicam hydrogel patch provided by the present invention comprises the steps:
(1) preparation pastille substrate: hydrophilic polymer framework material, wetting agent, cross-linking agent, the cross-linking regulator that will form in the described hydrogel matrix add in the deionized water, and mix homogeneously obtains the I phase; With the lornoxicam organic solvent dissolution, and add penetrating agent, obtain the II phase; The I phase is mixed mutually with II, and rotary evaporation is removed organic solvent under 20-80 ℃ of condition, obtains the pastille hydrogel matrix;
(2) adhered layer preparation: the solution that will form the pressure sensitive adhesive of adhered layer evenly is coated with exhibition on backing layer, in 60-80 ℃ of oven dry, cools off for subsequent use;
(3) pastille substrate is added on the adhered layer, covers protective layer, namely get described Lornoxicam hydrogel patch.
The present invention accumulates transit dose as evaluation index with lornoxicam, and carries out pharmacodynamic study with the screening technique of isolated rat skin permeation test in vitro as patch penetrating agent and substrate.The result confirms that Lornoxicam hydrogel patch can be at the continual and steady release medicine of in setting time, and the release amount is large, and safe ready, side effect are little.
Description of drawings
Fig. 1 is the in-vitro percutaneous accumulation penetration curve of Lornoxicam hydrogel patch among the embodiment 8 (content of dispersion is every square centimeter of lornoxicam 0.5mg).
Fig. 2 is the in-vitro percutaneous accumulation penetration curve of Lornoxicam hydrogel patch among the embodiment 8 (content of dispersion is every square centimeter of lornoxicam 1mg).
Fig. 3 is Lornoxicam hydrogel patch mice ear experimental result picture among the embodiment 9.
Fig. 4 is Lornoxicam hydrogel patch mouse writhing experimental result picture among the embodiment 9.
The specific embodiment
Below by specific embodiment foregoing of the present invention is described in further detail, embodiment only is indicative, means that never it limits the scope of the invention by any way.But do not breaking away from the above-mentioned technical thought of the present invention basis, the various replacements of making according to ordinary skill knowledge and customary means or the modification of change include within the scope of the invention.
Experimental technique described in the following embodiment if no special instructions, is conventional method; Described reagent and material if no special instructions, all can obtain from commercial channels.
Embodiment 1, preparation Lornoxicam hydrogel patch
Pastille matrix components (every 100cm
2)
Lornoxicam (principal agent) 0.05g
PVP K90 (framework material) 1.05g
PVP K30 (framework material) 0.78g
Polyvinyl alcohol-124 (framework material) 0.26g
Aluminum chloride (cross-linking agent) 0.015g
Glycerol (wetting agent) 1.57g
Azone (penetrating agent) 1g
Propylene glycol (penetrating agent) 1g
Deionized water 8.35g
Preparation method:
(1) pastille substrate: will add deionized water in the PVP K90 of recipe quantity, PVP K30, polyvinyl alcohol-124, aluminum chloride, the glycerol, 90 ℃ of heated and stirred mix homogeneously, approximately 2 hours, progressively cooling was until gel formed at room temperature obtains the I phase; Lornoxicam is dissolved fully with an amount of DMF, add again azone and propylene glycol, obtain the II phase; The I phase is mixed mutually with II, remove DMF at 30-50 ℃ of rotary evaporation, namely obtain the pastille hydrogel matrix.(2) adhered layer preparation: acrylate solution evenly is coated with exhibition on backing layer, in 60～80 ℃ of oven dry, cools off for subsequent use.(3) the pastille hydrogel matrix is added on the backing layer, covers protective layer, shear packing, and get final product.
Embodiment 2, preparation Lornoxicam hydrogel patch
Pastille matrix components (every 100cm
2)
Lornoxicam (principal agent) 0.1g
PVP K90 (framework material) 1.05g
PVP K30 (framework material) 0.78g
Polyvinyl alcohol-124 (framework material) 0.26g
Aluminum chloride (cross-linking agent) 0.015g
Glycerol (wetting agent) 1.57g
Azone (penetrating agent) 1g
Propylene glycol (penetrating agent) 1g
Deionized water 8.35g
Preparation method is with embodiment 1.
Embodiment 3, preparation Lornoxicam hydrogel patch
Pastille matrix components (every 100cm
2)
Lornoxicam (principal agent) 0.05g
PVP K90 (framework material) 1.31g
PVP K30 (framework material) 0.98g
Polyvinyl alcohol-124 (framework material) 0.325g
Aluminum chloride (cross-linking agent) 0.018g
PEG400 (wetting agent) 2.12g
Azone (penetrating agent) 1g
Propylene glycol (penetrating agent) 1g
Deionized water 10.44g
Preparation method is with embodiment 1.
Pastille matrix components (every 100cm
2)
Lornoxicam (principal agent) 0.05g
PVP K90 (framework material) 2.3g
Polyvinyl alcohol-124 (framework material) 0.325g
Aluminum chloride (cross-linking agent) 0.018g
Glycerol (wetting agent) 2.12g
Azone (penetrating agent) 1g
Propylene glycol (penetrating agent) 1g
Deionized water 9.56g
Preparation method is with embodiment 1.
Pastille matrix components (every 100cm
2)
Lornoxicam (principal agent) 0.05g
PVP K90 (framework material) 1.31g
PVP K30 (framework material) 0.98g
Polyvinyl alcohol-124 (framework material) 0.325g
Glycerol (wetting agent) 2.12g
Azone (penetrating agent) 1g
Propylene glycol (penetrating agent) 1g
Deionized water 9.56g
Preparation method is with embodiment 1.
Embodiment 6, preparation Lornoxicam hydrogel patch
Pastille matrix components (every 100cm
2)
Lornoxicam (principal agent) 0.05g
PVP K90 (framework material) 1.31g
PVP K30 (framework material) 0.98g
Polyvinyl alcohol-124 (framework material) 0.325g
Glycerol (wetting agent) 2.12g
Lauryl alcohol (penetrating agent) 1g
Propylene glycol (penetrating agent) 1g
Deionized water 9.56g
Preparation method is with embodiment 1.
Embodiment 7, preparation Lornoxicam hydrogel patch
Pastille matrix components (every 100cm
2)
Lornoxicam (principal agent) 0.05g
PVP K90 (framework material) 1.31g
PVP K30 (framework material) 0.98g
Polyvinyl alcohol-124 (framework material) 0.325g
Glycerol (wetting agent) 2.12g
Lauryl alcohol (penetrating agent) 0.5g
Azone (penetrating agent) 0.5g
Propylene glycol (penetrating agent) 1g
Deionized water 9.56g
Preparation method is with embodiment 1.
Embodiment 8, preparation Lornoxicam hydrogel patch
Pastille matrix components (every 100cm
2)
Lornoxicam (principal agent) 0.05g
Sodium polyacrylate (framework material) 0.77g
Aluminum chloride (cross-linking agent) 0.015g
Glycerol (wetting agent) 4.62g
Tartaric acid (cross-linking regulator) 0.03g
Azone (penetrating agent) 1g
Propylene glycol (penetrating agent) 1g
Deionized water 10.45g
Preparation method:
(1) pastille substrate: will add deionized water in the sodium polyacrylate of recipe quantity, aluminum chloride, glycerol, the tartaric acid, mix homogeneously obtains the I phase; Lornoxicam is dissolved fully with an amount of DMF, add again azone and propylene glycol, obtain the II phase; The I phase is mixed mutually with II, and DMF is removed in the low-temperature rotary evaporation, namely obtains the pastille hydrogel matrix.(2) adhered layer preparation: acrylate solution evenly is coated with exhibition on backing layer, in 60～80 ℃ of oven dry, cools off for subsequent use.(3) the pastille hydrogel matrix quantitatively is added on the backing layer, covers protective layer, shear packing, and get final product.
The transdermal permeation in vitro of embodiment 9, Lornoxicam hydrogel patch
Get the lornoxicam patch (2.8cm of embodiment 1 and 2 preparations
2) stick on the horny layer of the rat skin of peeling off, then be fixed in the Franz diffusion cell of improvement, so that the skin corium of rat skin is towards receiving chamber.In accepting the pond, add the 6mL receiver media, constant temperature (37 ± 0.5 ℃), respectively at predetermined point of time 1,2,4,6,8,10,12,24,36, the 48h 5mL that takes a sample, fill into simultaneously isopyknic blank medium, sample is behind the 0.45um filtering with microporous membrane, discard just filtrate, get subsequent filtrate and measure at wavelength 377nm place by ultraviolet method.Calculate cumulative in vitro infiltration capacity Q and the steady-state permeation speed Js of lornoxicam.Consider the diversity between Corium Mus different parts and the individuality, each prescription repeats 6 times in the experiment.In-vitro percutaneous accumulation penetration curve as shown in Figure 1 and Figure 2.
Experimental result shows, 48 hours transdermal test in vitro cumulants of Lornoxicam hydrogel patch (content of dispersion is every square centimeter of lornoxicam 0.5mg) of embodiment 1 preparation are (319.1 ± 40.5) ug.cm
-2, cumulative percentage reaches 63.8%, and steady-state permeation speed is 8.43ug.cm
-2.h
-148 hours transdermal test in vitro cumulants of Lornoxicam hydrogel patch (content of dispersion is every square centimeter of lornoxicam 1mg) of embodiment 2 preparations are (330.3 ± 21.56) ug.cm
-2, cumulative percentage reaches 33.1%, and steady-state permeation speed is 6.80cm
-2.h
-1Relatively the two discovery improves merely dose and percutaneous rate and not exclusively proportional.It is that the patch of every square centimeter of lornoxicam 0.5mg can satisfy the application needs that plan is made content of dispersion.
Pharmacodynamic experiment in embodiment 10, the Lornoxicam hydrogel patch body
(1) the Lornoxicam hydrogel patch Dichlorodiphenyl Acetate causes the mouse writhing experiment.
Get 50 of mices, male and female half and half about body weight 20g, are divided into 5 groups at random: 3 dosage groups of patch (increasing dosage by the area that increases patch) and the suspension group of blank matrix group, embodiment 1 preparation.Successive administration 3 days, afterwards, each organizes mouse peritoneal injection acetum, the writhing number of times appears in each Mus in the record 15min, and (t checks to carry out statistical analysis, compare between group), medicine analgesic rate (%)=(negative control group writhing number of times-treatment group writhing number of times)/negative control group writhing number of times * 100%.Experimental result sees Table 1.
Table 1 mouse writhing method experimental result
(n=10)
Annotate: with the blank group comparison same period,
*P＜0.05,
*P＜0.01; The t check.
By above experimental result as can be known, lornoxicam 0.20-0.60mg/kg dosage group mouse writhing number of times reduces along with the increase of dosage, and the analgesia rate that Dichlorodiphenyl Acetate causes mice pain is respectively 34.8%, 60.3%, 79.0%; Compare with the blank group, have significant difference (p＜0.05, p＜0.01).The analgesia rate that the positive controls Dichlorodiphenyl Acetate causes mice pain is 62.9%, has significant difference (p＜0.01).Thus prompting, Lornoxicam hydrogel patch has the effect of very strong antagonism peripheral neuralgia.
(2) Lornoxicam hydrogel patch causes little mice pain experiment to hot plate method
Get 50 of female mices, about body weight 20g, be divided at random 5 groups: 3 dosage groups of patch and the suspension group of blank matrix group, embodiment 1 preparation.Successive administration 3 days afterwards, is tested by the standard hot plate method.Percentage rate %=(the front average pain threshold of average pain threshold-medication after the medication)/front average pain threshold * 100% of medication is improved in the threshold of pain.Experimental result sees Table 2.
Table 2 hot plate method experimental result
(n=10)
Annotate: with the blank group comparison same period
*P＜0.05; The t check.
By above experimental result as can be known, each administration group mice is compared there was no significant difference (p＞0.05) before the induced pain with the blank group to the threshold value of heat; After the administration during 60-120min, the time that the middle and high dosage group of lornoxicam mice licks metapedes presents in various degree and prolongs, and pain threshold improves, with the same period blank group compare, have significant difference (p＜0.05).But pain threshold falls after rise behind the middle dosage group 120min.The positive controls mice after administration during 60-90min, with the same period blank group compare, significant difference (p＜0.05) is arranged, pain threshold also falls after rise behind the 120min.Thus prompting, the analgesic effect of the lornoxicam patch group of high dose is better, and presents prolongation trend action time.
(3) the lornoxicam xylol causes the mice ear experiment
Get 50 of male mices, about body weight 22g, be divided at random 5 groups: 3 dosage groups of patch and the suspension group of blank matrix group, embodiment 1 preparation.The auris dextra administration is 3 days continuously, afterwards, is coated with dimethylbenzene 30uL in every mouse right ear tow sides, and the ear same area is laid auricle with the 6mm card punch in the left and right sides.Weigh, calculate ear swelling degree (mg) and suppression ratio (%).Swelling (mg)=auris dextra auricle heavy (mg)-left ear auricle heavy (mg), ear swelling suppression ratio %=(negative control group ear swelling degree one treatment group ear swelling degree)/negative control group ear swelling degree * 100% and with negative control group relatively.Experimental result sees Table 3.
Table 3 mice caused by dimethylbenzene xylene ear swelling test result
(n=10)
Annotate: with the blank group comparison same period
*P＜0.05,
*P＜0.01; The t check.
By above experimental result as can be known, cause scorching front each administration group mice and the threshold value of heat is compared there was no significant difference (p＞0.05) with the blank group; After causing inflammation, the ear swelling degree of lornoxicam 0.2-0.6mg/kg dosage group mice with the same period blank group compare, have significant difference (p＜0.05, p＜0.01).Positive controls mice ear degree with the same period blank group compare, significant difference (p＜0.05) is arranged.Thus prompting, lornoxicam patch group has certain antiinflammatory action.
Claims (2)
1. Lornoxicam hydrogel patch, take lornoxicam as active constituents of medicine, it is comprised of pastille substrate, adhered layer, backing layer and protective layer; Wherein, described pastille substrate comprises lornoxicam, hydrogel matrix, penetrating agent and organic solvent, and described organic solvent is dimethyl formamide;
Every square centimeter of lornoxicam 0.1-10mg of described Lornoxicam hydrogel patch;
The mass ratio of lornoxicam and hydrogel matrix is 1 in the described pastille substrate: 80-500; The quality of described penetrating agent accounts for the 10-20% of hydrogel matrix quality;
Described penetrating agent is selected from following at least one class: sulfoxide type, pyrrolones, azone, fatty acid, terpenes, amine, amide-type, cyclodextrin, aminoacid and phospholipid;
Described hydrogel matrix is comprised of following substances:
5-20% hydrophilic polymer framework material, 10-30% wetting agent, 0-0.3% cross-linking agent, 0-0.3% cross-linking regulator and 50-70% deionized water; Wherein, the content of cross-linking agent and cross-linking regulator all is not 0;
" % " equal representation quality percentage composition wherein;
Described hydrophilic polymer framework material is selected from following at least a: polyvinylpyrrolidone, polyvinyl alcohol, sodium polyacrylate, polyacrylamide, carbomer, hydroxyethyl-cellulose, hydroxypropyl cellulose, hypromellose, carboxymethyl cellulose, sodium carboxymethyl cellulose and sodium alginate;
Described wetting agent is selected from following at least a: glycerol, Polyethylene Glycol, sorbitol, propylene glycol and butanediol;
Described cross-linking agent is selected from following at least a: aluminium hydroxide, calcium hydroxide, hydroxy Al, aluminum chloride and calcium chloride;
Described cross-linking regulator is selected from following at least a: tartaric acid, citric acid, lactic acid and hydroxyl succinic acid;
Described adhered layer is comprised of pressure sensitive adhesive, described pressure sensitive adhesive be selected from following any one: Polyisobutylene PSA, silicone pressure-sensitive adhesive, acrylate pressure sensitive adhesive, polyacrylate pressure-sensitive and natural rubber;
Described backing layer is made by following any one material: clad aluminum foil, polyethylene, polrvinyl chloride, polypropylene, polystyrene, polyester, polyethylene terephthalate and non-woven fabrics;
Described protective layer is polyethylene, polystyrene, polypropylene, Merlon, separate paper or the fluorine material of processing through paraffin or Organosilicon Release Agent.
2. prepare the method for the described Lornoxicam hydrogel patch of claim 1, comprise the steps:
(1) preparation pastille substrate: the hydrophilic polymer framework material in the described hydrogel matrix of claim 1, wetting agent, cross-linking agent, cross-linking regulator are added in the deionized water, and mix homogeneously obtains the I phase; With the lornoxicam organic solvent dissolution, and add penetrating agent, obtain the II phase; The I phase is mixed mutually with II, and rotary evaporation is removed organic solvent under 20-80 ℃ of condition, obtains the pastille hydrogel matrix;
(2) adhered layer preparation: the solution that will form the pressure sensitive adhesive of adhered layer evenly is coated with exhibition on backing layer, in 60-80 ℃ of oven dry, cools off for subsequent use;
(3) pastille substrate is added on the adhered layer, covers protective layer, namely get described Lornoxicam hydrogel patch.
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| ES2705028T3 (en) * | 2011-07-21 | 2019-03-21 | Teikoku Seiyaku Kk | Water-based plaster |
| CN102626401B (en) * | 2012-04-28 | 2013-09-25 | 佛山拜澳生物科技有限公司 | Hydrogel paste and preparation method thereof |
| CN104622793A (en) * | 2013-11-12 | 2015-05-20 | 张峰 | Hydrogel patch for relieving seasonal eye irritation |
| CN106074459A (en) * | 2016-07-11 | 2016-11-09 | 雷春生 | A kind of lasting water-retaining type hydrogel plaster supports the preparation method of layer material |
| CN111773201A (en) * | 2020-08-19 | 2020-10-16 | 扬州中宝药业股份有限公司 | Etamsylate gel patch and preparation method thereof |
| CN114796100B (en) * | 2022-03-04 | 2023-09-22 | 中山大学 | Piroxicam gel emplastrum and preparation method thereof |
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