CN103099799B - Composite film-like preparation and preparation method thereof - Google Patents
Composite film-like preparation and preparation method thereof Download PDFInfo
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- CN103099799B CN103099799B CN201310046865.7A CN201310046865A CN103099799B CN 103099799 B CN103099799 B CN 103099799B CN 201310046865 A CN201310046865 A CN 201310046865A CN 103099799 B CN103099799 B CN 103099799B
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- medicine
- alkaline
- acid
- water
- film
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- 238000002360 preparation method Methods 0.000 title claims abstract description 52
- 239000002131 composite material Substances 0.000 title abstract 7
- 239000003814 drug Substances 0.000 claims abstract description 67
- 150000001875 compounds Chemical class 0.000 claims abstract description 31
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 21
- 239000000463 material Substances 0.000 claims abstract description 19
- 230000002378 acidificating effect Effects 0.000 claims abstract description 8
- 239000010408 film Substances 0.000 claims description 100
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 46
- 239000000470 constituent Substances 0.000 claims description 26
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 24
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 22
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical group O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 18
- 239000010409 thin film Substances 0.000 claims description 17
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical group [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 16
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 14
- 229920002521 macromolecule Polymers 0.000 claims description 11
- 239000003381 stabilizer Substances 0.000 claims description 11
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- KTGRHKOEFSJQNS-BDQAORGHSA-N (1s)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3h-2-benzofuran-5-carbonitrile;oxalic acid Chemical compound OC(=O)C(O)=O.C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 KTGRHKOEFSJQNS-BDQAORGHSA-N 0.000 claims description 8
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- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 7
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- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 6
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 6
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 5
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- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 4
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 4
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- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 4
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- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
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- PLXMOAALOJOTIY-FPTXNFDTSA-N Aesculin Natural products OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)[C@H]1Oc2cc3C=CC(=O)Oc3cc2O PLXMOAALOJOTIY-FPTXNFDTSA-N 0.000 description 1
- 206010006326 Breath odour Diseases 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
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- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
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- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 229930194931 Rhodexin Natural products 0.000 description 1
- 206010041235 Snoring Diseases 0.000 description 1
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 description 1
- 229960004005 amlodipine besylate Drugs 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 229960004415 codeine phosphate Drugs 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 230000013872 defecation Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229960004192 diphenoxylate Drugs 0.000 description 1
- HYPPXZBJBPSRLK-UHFFFAOYSA-N diphenoxylate Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 HYPPXZBJBPSRLK-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229940048396 escitalopram 5 mg Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000007455 ileostomy Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229960003088 loratadine Drugs 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 230000003232 mucoadhesive effect Effects 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229960002244 promethazine hydrochloride Drugs 0.000 description 1
- XXPDBLUZJRXNNZ-UHFFFAOYSA-N promethazine hydrochloride Chemical compound Cl.C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 XXPDBLUZJRXNNZ-UHFFFAOYSA-N 0.000 description 1
- 238000004537 pulping Methods 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 229940096805 simvastatin 5 mg Drugs 0.000 description 1
- 229940013618 stevioside Drugs 0.000 description 1
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 1
- 235000019202 steviosides Nutrition 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001779 taste bud Anatomy 0.000 description 1
- 229940125725 tranquilizer Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 229940102192 zolmitriptan 2.5 mg Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention discloses a composite film-like preparation and a preparation method thereof. The composite film-like preparation comprises a composite strip-like film tape and a treatment effective amount of active medicament loaded on at least one of an acidic strip-like film tape, a blank tape or an alkaline strip-like film tape of the composite strip-like film tape, wherein the composite strip-like film tape comprises the acidic strip-like film tape, the blank tape and the alkaline strip-like film tape, and the acidic strip-like film tape, the blank tape and the alkaline strip-like film tape are sequentially and mutually arranged at intervals and connected into a whole; the acidic strip-like film tape takes a high water-soluble polymer film-forming material as a main body, and contains an acidizer accounting for 1-20% of the weight of the film tape; the alkaline strip-like film tape takes the high water-soluble polymer film-forming material as the main body and contains an alkaline agent accounting for 1-20% of the weight of the film tape; and the blank tape comprises the high water-soluble polymer film-forming material. The composite film-like preparation disclosed by the invention can accelerate dissolution and reduce the interaction among different components in a compound.
Description
Technical field
The present invention relates to a kind of medicine film preparation and preparation method thereof.
Background technology
Medicine film preparation is as far back as i.e. existing much research of nineteen seventies, as tranquilizer film (Chinese Journal of Pharmaceuticals, 1976,12(19)), diphenoxylate medicine film (Chinese Journal of Pharmaceuticals, 1976,12(22)), external applied contraceptive film (Chinese Journal of Pharmaceuticals, 1977,4-5(45)), nitroglycerin medicine film (Chinese Journal of Pharmaceuticals, 1977,12(5)), rhodexin film (Chinese Journal of Pharmaceuticals, 1980,4(18)), clonidine sustained release film formulation (Chinese Journal of Pharmaceuticals, 1981,3(141)) etc.Chinese Pharmacopoeia is also recorded (Pharmacopoeia of People's Republic of China 1995 editions, 2000 editions, 2005 editions, 2010 editions) using membrane as official preparation.
Yet membrane is thin, light, little, the easy moisture absorption, thereby to having relatively high expectations of packing, should be easy to use, should be able to guarantee again the quality of medicine, and domestic current packaged form is used inconvenience, not attractive in appearance; The drug loading of membrane not high (general 30～60mg is following), and to carry out taste masking.These have all restricted development and the application of membrane.
In recent years, membrane development is swift and violent, and calendar year 2001 Pfizer company has released
with
product, for anti-halitosis in advance.Novartis company has also released folk prescription or the compound oral membrane that a series of effective ingredient are diphenhydramine, phenylephrine and dextromethorphan, for catching a cold, prevention and the treatment of cough or rhinitis.There is subsequently more pelliculae pro cavo oris product to occur.Biofilm company is the product for physical strength reinforcing, vitimin supplement, hypersexuality and appetite-suppressing by pelliculae pro cavo oris technology.Ondansetron (ondansetron) membrane of MonosolRx company exploitation and its oral cavity quick disintegrating slice (
) bioequivalence, in July, 2010, obtain the approval of FDA.Passion for Life Healthcare company develops and the product of the prevention snoring of a kind of uniqueness of having gone on the market
voglibose (voglibose) membrane of Japan Kyukyu yakuhin Kogyo K.K. development, releases in August, 2006, for improving diabetics postprandial hyperglycemia.
Patent about membrane also emerges in an endless stream, there is the edible water-soluble film (CN101516331A) that contains foam reducing flavoring agent, film bandage (CN101389309A) for mucosal administration of actives, high dose film compositions and preparation method thereof (CN101616660A), polymer-based films and drug delivery system prepared therefrom (CN101668519A), the preparation method of edible film (CN101744791A), the film (CN101346135A) of the adjusted pH sending for activating agent, film bandage (CN101389309A) for mucosal administration of actives, non-mucoadhesive film dosage forms (CN101626756A), disintegrable oral films (CN101384249A), membrane that can be Orally administered (CN101621990A), for neuroleptic, the oral fast that can not be spued collapses film (CN101287445A), instant capacity membrane (CN100396332C) etc.The inventor has also applied for the production machine of membrane, the patent of the new packaged form of the packaging machine of membrane, membrane, to promote membrane development at home.
The inventor, in the R&D process of membrane, usually runs into following two problems:
1) active constituents of medicine usually has bitterness, needs taste masking.Adding effervescent is a kind of known comparatively effectively method to modify taste, effervescent is comprised of acidizer (as citric acid, tartaric acid, fumaric acid, adipic acid and malic acid etc.) and alkaline agent (as sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate and calcium carbonate etc.), after entering water, both react, produce a large amount of carbon dioxide, it can temporarily benumb taste bud and taste masking.But in preparing the process of membrane, normally adjuvant is scattered in aqueous solvent together with active constituents of medicine, repastes cloth drying and forming-film.Acidizer in effervescent and alkaline agent react in process with slurry, cannot retain in film simultaneously.2), while preparing compound recipe membrane, because the physicochemical property of the active component in compound recipe is different, applicable prescription and technique are different, influence each other sometimes.The compound recipe being for example comprised of A and B, acidic excipient can strengthen the stability of A material, has but affected the dissolubility of B material, makes B in pulping process, be difficult for being uniformly dispersed.
Summary of the invention
One of the object of the invention is to be to provide a kind of compound membranaceous preparation and preparation method thereof, the defect existing to overcome prior art, meets clinical needs.
Two of object of the present invention is to provide a kind of compound strip film band for medicine carrying, for the preparation of membranaceous preparation.
Described compound strip film band, comprises acid strip film band, blank tape and alkaline strip film band, described acid strip film band, blank tape and and alkaline strip film band successively mutually interval arrange and be connected;
Described acid strip film band, take highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20%, preferably 2～10% acidizer, and described acidizer is selected from citric acid, tartaric acid, fumaric acid, maleic acid, adipic acid or malic acid;
Described alkaline strip film band, take highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20%, preferably 2～10% alkaline agent, and described alkaline agent is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or calcium carbonate;
Described blank tape comprises highly-water-soluble macromolecule filming material;
Preferably, described acid strip film band, blank tape and alkaline strip film band, also comprise more than one in plasticizer, correctives, coloring agent or stabilizing agent;
Preferably, described acid strip film band comprises the component of following percentage by weight:
Highly-water-soluble macromolecule filming material 40～98%, preferably 65～85%;
Acidizer 1～20%, preferably 2～10%;
Plasticizer 0～20%, preferably 0～5%;
Correctives 0～30%, preferably 5～15%;
Coloring agent 0～5%, preferably 0.1～5%;
Stabilizing agent 0～5%, preferably 0～1%;
Described alkaline strip film band comprises the component of following percentage by weight:
Highly-water-soluble macromolecule filming material 40～98%, preferably 65～85%;
Alkaline agent 1～20%, preferably 2～10%;
Plasticizer 0～20%, preferably 0～5%;
Correctives 0～30%, preferably 5～15%;
Coloring agent 0～5%, preferably 0.1～5%;
Stabilizing agent 0～5%, preferably 0～1%.
A compound membranaceous preparation, comprises described compound strip film band and loads on more than one the active medicine for the treatment of effective dose in acid strip film band, blank tape or the alkaline strip film band of described compound strip film band;
That is, active medicine can load on acid strip film band, blank tape and alkaline strip film band simultaneously, also can load on acid strip film band, blank tape and alkaline strip film band any one;
Preferred:
Described acid strip film band comprises the component of following percentage by weight:
Active constituents of medicine 0～30%, preferably 5～30%;
Highly-water-soluble macromolecule filming material 40～98%, preferably 50～75%;
Acidizer 1～20%, preferably 2～10%;
Plasticizer 0～20%, preferably 0～5%;
Correctives 0～30%, preferably 5～15%;
Coloring agent 0～5%, preferably 0.1～5%;
Stabilizing agent 0～5%, preferably 0～1%;
Described alkaline strip film band comprises the component of following percentage by weight:
Active constituents of medicine 0～30%, preferably 5～30%;
Highly-water-soluble macromolecule filming material 40～98%, preferably 50～75%;
Alkaline agent 1～20%, preferably 2～10%;
Plasticizer 0～20%, preferably 0～5%;
Correctives 0～30%, preferably 5～15%;
Coloring agent 0～5%, preferably 0.1～5%;
Stabilizing agent 0～5%, preferably 0～1%;
In the gross weight of described compound membranaceous preparation, the content of described active constituents of medicine is 1～30%, preferably 4.0～30%;
Described membranaceous preparation thickness is 0.04～0.20mm, preferably 0.06～0.10mm;
Described active constituents of medicine, so long as in water, ethanol and acetone kind solvent solubilized or dispersible, all can load in described thin film, include, but are not limited to the medicine of donepezil, Zolmitriptan, loperamide, simvastatin, olanzapine, diphenhydramine, cetirizine hydrochloride, scopolamine hydrobromide, chlorphenamine maleate, voglibose, Lizakuputan benzoate, Zolpidemtar Trate, Ondansetron Hydrochloride, asenapine, escitalopram oxalate, vaccine or polypeptide etc.;
Described water soluble polymer filmogen comprises more than one in polyvinyl alcohol (PVA), hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), sodium alginate, CMC-Na, polyoxyethylene (PEO), Bletilla glucomannan, maltodextrin, corn starch or carrageenan;
Described acidizer is selected from citric acid, tartaric acid, fumaric acid, maleic acid, adipic acid or malic acid;
Described alkaline agent is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or calcium carbonate;
Described plasticizer comprises more than one in Polyethylene Glycol (PEG), glycerol or Tween 80;
Described correctives comprises more than one in sweeting agent, acidic flavoring agent, aromatic, resin macromolecular material, lecithin, cephalin or phosphatidic acid etc.;
Described stabilizing agent is selected from sodium sulfite, sodium sulfite, EDTA-2Na, BHA, BHT or vitamin E etc.;
Described coloring agent is selected from titanium dioxide, various natural pigment or artificial color etc.;
Described active constituents of medicine, so long as at water, solubilized or dispersible in ethanol and acetone kind solvent, all can load in described thin film, include, but are not limited to loratadine, Menglusitena, codeine phosphate, promethazine hydrochloride, risperidone, Amlodipine Besylate Tablet, donepezil, Zolmitriptan, loperamide, simvastatin, olanzapine, diphenhydramine, cetirizine hydrochloride, scopolamine hydrobromide, chlorphenamine maleate, voglibose, Lizakuputan benzoate, Zolpidemtar Trate, Ondansetron Hydrochloride, asenapine, escitalopram oxalate, the medicine of vaccine or polypeptide etc.,
Described water soluble polymer filmogen comprises more than one in polyvinyl alcohol (PVA), hydroxypropyl emthylcellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinylpyrrolidone (PVP), sodium alginate, CMC-Na, polyoxyethylene (PEO), Bletilla glucomannan, maltodextrin, corn starch or carrageenan;
Described acidizer is selected from citric acid, tartaric acid, fumaric acid, maleic acid, adipic acid or malic acid;
Described alkaline agent is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or calcium carbonate;
Described plasticizer comprises more than one in Polyethylene Glycol (PEG), glycerol or Tween 80;
Described correctives comprises more than one in sweeting agent, acidic flavoring agent, aromatic, resin macromolecular material, lecithin, cephalin or phosphatidic acid etc.;
Described stabilizing agent is selected from sodium sulfite, sodium sulfite, EDTA-2Na, BHA, BHT or vitamin E etc.;
Preferably, described blank tape also comprises coloring agent and stabilizing agent;
Described stabilizing agent is selected from sodium sulfite, sodium sulfite, EDTA-2Na, BHA, BHT or vitamin E etc.;
Described coloring agent is selected from titanium dioxide, various natural pigment or artificial color etc.;
The preparation method of described membranaceous preparation, comprises the steps:
Term " interval coating successively ", refers to, and one is serosity A, and other one is serosity B;
Further, there is the preparation method of the described membranaceous preparation of blank tape, comprise the steps:
(1) active constituents of medicine, acidizer and other components except active constituents of medicine and acidizer are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes acid serosity A;
(2) active component, alkaline agent and other components except active constituents of medicine and acidizer are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes alkaline slurry B;
(3) active component and other components except active constituents of medicine are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes blank serosity C;
(3) serosity A and white serosity C and serosity B sky successively interval are coated in dull and stereotyped upper, due to solvent expansion effect, are complex as a whole, obtain medicine carrying thin film;
Term " interval coating successively ", refers to, and both sides are respectively serosity A and serosity B, and centre is serosity C;
(4) medicine carrying thin film step (3) being obtained, at the temperature of 50～90 ℃, dry 5～30min, obtains described compound membranaceous preparation.
The using method of membranaceous preparation of the present invention is identical with conventional membrane.
The beneficial effect of membranaceous preparation of the present invention is:
The inventor accumulates by a large amount of experiments, when coating, is coated with two or more simultaneously, finally forms more than one compound membrane.Many film can be realized following specific purposes: 1) make effervescent film: in a film, contain the acidizers such as citric acid, tartaric acid, article one, in film, contain the alkaline agents such as sodium carbonate, sodium bicarbonate or calcium carbonate, after meeting water, become effervescent film, produce a large amount of bubbles, benumb olfactory sensation and taste masking, and can accelerate stripping.2) can reduce influencing each other between heterogeneity in compound recipe, and research and development are simplified.In addition, many films also can be rendered as double-colored or polychrome film, during especially for children preparation, increase the aesthetic feeling of medicine, improve the interest that child takes medicine.
Accompanying drawing explanation
Fig. 1 is compound strip film band structure schematic diagram.
Fig. 2 is Zolmitriptan film stripping curve.
Fig. 3 is escitalopram oxalate film stripping curve.
Fig. 4 is simvastatin film stripping curve.
Fig. 5 is loperamide film stripping curve.
The specific embodiment
Referring to Fig. 1, described compound strip film band, comprises acid strip film band 1, blank tape 2 and alkaline strip film band 3, and described acid strip film band 1, blank tape 2 and alkaline strip film band 3 successively mutual interval arrange and be connected;
Embodiment 1
1) get distilled water 600ml, add successively while stirring glycerol 10g, citric acid 20g, aspartame 20g and allured red pigment 0.2g, finally add PVA150g, be stirred into full-bodied solution, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity A.
2) get PVA33g adding distil water 100ml, be stirred into full-bodied solution, then add allured red pigment 0.03g and sunset yellow 0.06g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity B.
3) get distilled water 600ml, add successively while stirring glycerol 10g, sodium bicarbonate 20g, acesulfame potassium 20g and allured red pigment 0.2g, finally add PVA150g, be stirred into full-bodied solution, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity C.
4) serosity A, B and C are added in dosing tank, this dosing tank is comprised of three parallel sulculuses, and width is respectively 1.2,0.2,1.2cm, and the spacer width between sulculus is 0.1cm.Start coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 80 ℃ of dry 10min, due to solvent expansion effect, 3 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt again knurling rolls embossing, cut into after certain size, from stainless steel band, peel off, pack and get final product.This film preparation is comprised of trichroism, aesthetic in appearance, after chance water, becomes effervescent film, produces a large amount of bubbles, and stripping is rapid.
Embodiment 2
Zolmitriptan film
1) get Zolmitriptan 24g adding distil water 600ml, dispersed with stirring is even, then adds while stirring xylitol 10g, glycerol 8g, titanium dioxide 8g, EDTA0.1g and tartaric acid 4g, finally add PVP56g and PVA90g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity A.
2) get Zolmitriptan 4.8g adding distil water 120ml, stir, be uniformly dispersed, then add while stirring xylitol 2g, glycerol 1.6g and titanium dioxide 1.6g, finally add PVP12g and PVA18g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity B.
3) get Zolmitriptan 24g adding distil water 600ml, stir, be uniformly dispersed, add while stirring again xylitol 10g, glycerol 8g, titanium dioxide 8g, EDTA0.1g and sodium carbonate 4g, finally add PVP56g and PVA90g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity C.
Serosity A, B, C are added in dosing tank, and this dosing tank is comprised of three parallel sulculuses, and width is respectively 1.2,0.2,1.2cm, and the spacer width between sulculus is 0.1cm.Start coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 80 ℃ of dry 10min, due to solvent expansion effect, 3 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt again knurling rolls embossing, according to assay result, cut into after certain size, from stainless steel band, peel off, pack and get final product.
The compound herbal membrane preparation obtaining, thickness is 0.07mm, every containing Zolmitriptan 2.5mg.Be applicable to with/without the migrainous acute treatment of tendency.Once take a slice.If symptom continue need medication for the first time after 2 hours secondary take medicine, or recurrence, takes medicine still effective again, in 24 hours, maximal dose must not surpass 15mg.
This medicine film preparation is aesthetic in appearance.After meeting water, become effervescent film, produce a large amount of bubbles, stripping is rapid, and sense of taste is better.
Get 6 of this product, each clip becomes the thin film of 1cm * 1cm size, the stainless steel silk that is 2.0mm with two-layer sieve aperture internal diameter respectively folder, according to the method (two appendix X A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, check, observe and record that membrane all dissolves and by the time of screen cloth.It is very fast that this product is dissolved the time limit, is 40 ± 3s.
Get 6 of this product, with paperclip, clamp respectively, adopt dissolution method (two appendix X C the 3rd methods of Chinese Pharmacopoeia version in 2010) device, take water 100ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately, respectively in the time of 1,2,3,5,10 and 15 minute, get solution 1ml, filter, get subsequent filtrate, according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010), measure and calculate the stripping quantity of every.Stripping curve is shown in accompanying drawing 2.From accompanying drawing 2, this product In Vitro Dissolution is very fast, in 3min, dissolves completely.
Embodiment 3
Escitalopram oxalate film
1) get escitalopram oxalate 60g adding distil water 600ml, stir, be uniformly dispersed, add while stirring again aspartame 10g, sucralose 20g, erythrosine 0.2g, BHT0.2g and citric acid 10g, finally add HPMC80g and HPC20g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity A.
2) get escitalopram oxalate 10g adding distil water 100ml, stir, be uniformly dispersed, then add while stirring acesulfame potassium 5g, BHT0.03g and the red 0.03g of temptation, finally add HPMC18g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity B.
3) get escitalopram oxalate 60g adding distil water 600ml, stir, be uniformly dispersed, add while stirring again aspartame 10g, sucralose 20g, BHT0.2g, erythrosine 0.2g and potassium bicarbonate 10g, finally add HPMC80g and HPC20g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity C.
Serosity A, B, C are added in dosing tank, and this dosing tank is comprised of three parallel sulculuses, and width is respectively 1.2,0.2,1.2cm, and the spacer width between sulculus is 0.1cm.Start coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 80 ℃ of dry 10min, due to solvent expansion effect, 3 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt again knurling rolls embossing, according to assay result, cut into after certain size, from stainless steel band, peel off, pack and get final product.
The compound herbal membrane preparation obtaining, thickness is 0.08mm, every containing escitalopram 5mg.Be used for the treatment of depression.Every day 1 time, each 2.
This medicine film preparation is comprised of trichroism, novelty aesthetic in appearance.After meeting water, become effervescent film, produce a large amount of bubbles, stripping is rapid, and sense of taste is better.
Get 6 of this product, each clip becomes the thin film of 1cm * 1cm size, the stainless steel silk that is 2.0mm with two-layer sieve aperture internal diameter respectively folder, according to the method (two appendix X A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, check, observe and record that membrane all dissolves and by the time of screen cloth.It is very fast that this product is dissolved the time limit, is 46 ± 4s.
Get 6 of this product, with paperclip, clamp respectively, adopt dissolution method (two appendix X C the 3rd methods of Chinese Pharmacopoeia version in 2010) device, take water 100ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately, respectively in the time of 1,2,3,5,10 and 15 minute, get solution 1ml, filter, get subsequent filtrate, according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010), measure and calculate the stripping quantity of every.Stripping curve is shown in accompanying drawing 3.From accompanying drawing 3, this product In Vitro Dissolution is very fast, in 3min, dissolves completely.
Embodiment 4
Simvastatin film
1) get simvastatin 40g adding distil water 600ml, stir, be uniformly dispersed, then add while stirring stevioside 18g, light blue 0.2g, calcium carbonate 20g and vitamin E2 g, finally add PEO120g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity A.
2) get simvastatin 5g adding distil water 100ml, stir, be uniformly dispersed, then add while stirring acesulfame potassium 5g and light blue 0.03g, finally add PVP5g and HPC18g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity B.
2) get PEO80g adding distil water 300ml, stir, then add malic acid 20g and light blue 0.1g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity C.
Serosity A, B, C are added in dosing tank, and this dosing tank is comprised of three parallel sulculuses, and width is respectively 1.2cm, 0.2cm and 0.6cm, and the spacer width between sulculus is 0.1cm.Start coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 60 ℃ of dry 20min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt again knurling rolls embossing, according to assay result, cut into after certain size, from stainless steel band, peel off, pack and get final product.
Many medicine film preparations that obtain, thickness is 0.08mm, every containing simvastatin 5mg.For hypercholesterolemia and coronary heart disease treatment.Hypercholesterolemiapatients patients is general to be begun to take dosage is 10mg every day, night decoction being taken at a draught.For the patient of the mild to moderate rising of cholesterol levels, beginning to take dosage is 5mg every day.More than if need to adjust, dosage answers interval surrounding, maximal dose is 40mg every day, night decoction being taken at a draught.When low-density lipoprotein cholesterol level is down to 75mg/dL(1.94mmol/L) or total cholesterol level be down to 140mg/dL(3.6mmol/L) when following, should lower taking dose.Patients with coronary heart disease can be taken 20mg every night as initial dose.
This medicine film preparation is aesthetic in appearance.After meeting water, become effervescent film, produce a large amount of bubbles, stripping is rapid, and sense of taste is better.
Get 6 of this product, each clip becomes the thin film of 1cm * 1cm size, the stainless steel silk that is 2.0mm with two-layer sieve aperture internal diameter respectively folder, according to the method (two appendix X A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, check, observe and record that membrane all dissolves and by the time of screen cloth.It is very fast that this product is dissolved the time limit, is 39 ± 4s.
Get 6 of this product, with paperclip, clamp respectively, adopt dissolution method (two appendix X C the 3rd methods of Chinese Pharmacopoeia version in 2010) device, take water 100ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately, respectively in the time of 1,2,3,5,10 and 15 minute, get solution 1ml, filter, get subsequent filtrate, according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010), measure and calculate the stripping quantity of every.Stripping curve is shown in accompanying drawing 4.From accompanying drawing 4, this product In Vitro Dissolution is very fast, in 3min, dissolves completely.
Embodiment 5
Loperamide film
1) get loperamide 10g adding distil water 500ml, dispersed with stirring is even, then adds while stirring cyclamate 20g, PEG40010g, titanium dioxide 10g, vitamin E2 g and maleic acid 20g, finally add HPMC128g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity A.
2) get HPMC28g adding distil water 80ml, stir, then add saccharin sodium 3g and titanium dioxide 2g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity B.
3) get loperamide 10g adding distil water 500ml, dispersed with stirring is even, add while stirring again cyclamate 20g, PEG40010g, titanium dioxide 10g, vitamin E2 g and sodium bicarbonate 20g, finally add HPMC80g, sodium alginate 20g and CMC-Na28g, stir, cross 80 mesh sieves, remove insoluble matter, vacuum defoamation.Obtain serosity C.
Serosity A, B, C are added in dosing tank, and this dosing tank is comprised of three parallel sulculuses, and width is respectively 1.2cm, 0.2cm and 1.2cm, and the spacer width between sulculus is 0.1cm.Start coating drying machine, with coating blade coating, the extension of film liquid on stainless steel band, 60 ℃ of dry 10min, due to solvent expansion effect, 2 serosity are complex as a whole, and obtain medicine carrying thin film; Adopt again knurling rolls embossing, according to assay result, cut into after certain size, from stainless steel band, peel off, pack and get final product.
The medicine film preparation obtaining, thickness is 0.06mm, every containing loperamide 1mg.Can be used for various acute and chronic diarrhoea.To ileostomy patient, can be used to increase the thick hardness of stool, reduce number of times and the quantity of defecation.Adult takes 2 times every day, each 1.
This film preparation is aesthetic in appearance.After meeting water, become effervescent film, produce a large amount of bubbles, stripping is rapid, and sense of taste is better.
Get 6 of this product, each clip becomes the thin film of 1cm * 1cm size, the stainless steel silk that is 2.0mm with two-layer sieve aperture internal diameter respectively folder, according to the method (two appendix X A of Chinese Pharmacopoeia version in 2010) under disintegration inspection technique tablet item, check, observe and record that membrane all dissolves and by the time of screen cloth.It is very fast that this product is dissolved the time limit, is 33 ± 4s.
Get 6 of this product, with paperclip, clamp respectively, adopt dissolution method (two appendix X C the 3rd methods of Chinese Pharmacopoeia version in 2010) device, take water 100ml as dissolution medium, rotating speed is per minute 50 to turn, from test sample contact dissolution medium, timing immediately, respectively in the time of 0.5,1,2,3,5 and 10 minute, get solution 1ml, filter, get subsequent filtrate, according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010), measure and calculate the stripping quantity of every.Stripping curve is shown in accompanying drawing 5.From accompanying drawing 5, this product In Vitro Dissolution is very fast, in 2min, dissolves completely.
Claims (8)
1. compound membranaceous preparation, is characterized in that, comprises acid strip film band, blank tape and alkaline strip film band, and described acid strip film band, blank tape and alkaline strip film band arrange and are connected in space successively;
Described acid strip film band, take highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20% acidizer, and described alkaline strip film band, take highly-water-soluble macromolecule filming material as main body, with film band weighing scale, contains 1～20% alkaline agent; Described blank tape comprises highly-water-soluble macromolecule filming material;
Preparation method, comprises the steps:
(1) active constituents of medicine, acidizer and other components except active constituents of medicine and acidizer are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes acid serosity A;
(2) active constituents of medicine, alkaline agent and other components except active constituents of medicine and alkaline agent are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes alkaline slurry B;
(3) active constituents of medicine and other components except active constituents of medicine are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes blank serosity C;
(4) serosity A, blank serosity C and serosity B are coated in to flat board above in interval successively, due to solvent expansion effect, are complex as a whole, obtain medicine carrying thin film;
(5) medicine carrying thin film step (4) being obtained, at the temperature of 50～90 ℃, dry 5～30min, obtains described compound membranaceous preparation;
Described active medicine loads on acid strip film band, blank tape and alkaline strip film band simultaneously, or loads on acid strip film band, blank tape and alkaline strip film band any one.
2. compound membranaceous preparation according to claim 1, it is characterized in that, described acidizer is selected from citric acid, tartaric acid, fumaric acid, maleic acid, adipic acid or malic acid, and described alkaline agent is selected from sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate or calcium carbonate.
3. compound membranaceous preparation according to claim 1, is characterized in that, described acid strip film band, alkaline strip film band and described blank tape are also comprising more than one in plasticizer, correctives, coloring agent or stabilizing agent.
4. compound membranaceous preparation according to claim 3, is characterized in that, described acid strip film band comprises the component of following percentage by weight:
Described alkaline strip film band comprises the component of following percentage by weight:
In the gross weight of described compound membranaceous preparation, the content of described active constituents of medicine is 1～30%.
5. compound membranaceous preparation according to claim 3, is characterized in that, described acid strip film band comprises the component of following percentage by weight:
Described alkaline strip film band comprises the component of following percentage by weight:
In the gross weight of described compound membranaceous preparation, the content of described active constituents of medicine is 4.0～30%.
6. compound membranaceous preparation according to claim 5, it is characterized in that, described active constituents of medicine is the medicine of donepezil, Zolmitriptan, loperamide, simvastatin, olanzapine, diphenhydramine, cetirizine hydrochloride, scopolamine hydrobromide, chlorphenamine maleate, voglibose, Lizakuputan benzoate, Zolpidemtar Trate, Ondansetron Hydrochloride, asenapine, escitalopram oxalate, vaccine or polypeptide.
7. compound membranaceous preparation according to claim 5, it is characterized in that, described highly-water-soluble macromolecule filming material is selected from more than one in polyvinyl alcohol, hydroxypropyl emthylcellulose, hydroxy propyl cellulose, polyvinylpyrrolidone, sodium alginate, CMC-Na, polyoxyethylene, Rhizoma Bletillae gel, maltodextrin, corn starch or carrageenan;
Described plasticizer is selected from more than one in Polyethylene Glycol, glycerol or Tween 80;
Described correctives is selected from more than one in sweeting agent, acidic flavoring agent, aromatic, resin macromolecular material, lecithin, cephalin or phosphatidic acid;
Described stabilizing agent is selected from sodium sulfite, sodium sulfite, EDTA-2Na, BHA, BHT or vitamin E;
Described coloring agent is selected from titanium dioxide, various natural pigment or artificial color.
8. according to the preparation method of the membranaceous preparation described in claim 1～7 any one, comprise the steps:
(1) active constituents of medicine, acidizer and other components except active constituents of medicine and acidizer are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes acid serosity A;
(2) active constituents of medicine, alkaline agent and other components except active constituents of medicine and alkaline agent are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes alkaline slurry B;
(3) active constituents of medicine and other components except active constituents of medicine are mixed with water, the water slip that acquisition weight concentration is 15～35%, makes blank serosity C;
(4) serosity A, blank serosity C and serosity B are coated in to flat board above in interval successively, obtain medicine carrying thin film;
(5) medicine carrying thin film step (4) being obtained, at the temperature of 50～90 ℃, dry 5～30min, obtains described compound membranaceous preparation.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12138353B2 (en) | 2016-12-20 | 2024-11-12 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
| US12329862B2 (en) | 2018-06-20 | 2025-06-17 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103142559A (en) * | 2013-02-21 | 2013-06-12 | 上海现代药物制剂工程研究中心有限公司 | Risperidone film-like preparation |
| CN103142560A (en) * | 2013-02-21 | 2013-06-12 | 上海现代药物制剂工程研究中心有限公司 | Montelukast sodium film-like preparation |
| TR201509009A1 (en) * | 2014-12-11 | 2017-02-21 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | A thin film strip of asenapine |
| CN106176691A (en) * | 2016-08-31 | 2016-12-07 | 齐鲁制药有限公司 | A kind of molten membrane of escitalopram oxalate mouth and preparation method thereof |
| EP3558276B1 (en) | 2016-12-20 | 2024-11-06 | LTS Lohmann Therapie-Systeme AG | Transdermal therapeutic system containing asenapine and polysiloxane or polyisobutylene |
| CN110799180A (en) | 2017-06-26 | 2020-02-14 | 罗曼治疗系统股份公司 | Transdermal therapeutic system containing asenapine and siloxane acrylic hybrid polymer |
| BR112020026099A2 (en) | 2018-06-20 | 2021-03-23 | Lts Lohmann Therapie-Systeme Ag | transdermal therapeutic system containing asenapine |
| CN114632073A (en) * | 2020-12-15 | 2022-06-17 | 南京海辰药业股份有限公司 | Propofol fumarate and tenofovir oral instant film agent and preparation method thereof |
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| CN1658835A (en) * | 2002-06-04 | 2005-08-24 | Lts罗曼治疗方法有限公司 | Film-shaped, dissolvable preparations for active substance release and method for the production thereof |
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| CN1658835A (en) * | 2002-06-04 | 2005-08-24 | Lts罗曼治疗方法有限公司 | Film-shaped, dissolvable preparations for active substance release and method for the production thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12138353B2 (en) | 2016-12-20 | 2024-11-12 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
| US12329862B2 (en) | 2018-06-20 | 2025-06-17 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
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