CN1829490A

CN1829490A - Film comprising therapeutic agents

Info

Publication number: CN1829490A
Application number: CN 200480022053
Authority: CN
Inventors: 托德·迈巴赫
Original assignee: Individual
Current assignee: Individual
Priority date: 2003-07-01
Filing date: 2004-06-30
Publication date: 2006-09-06

Abstract

The present invention is related to the composition and methods of manufacture of orally-dissolvable, edible films as a vehicle for the non-invasive administration of nitroglycerin, as well as other therapeutic agents either with or without nitroglycerin, through the mucosal tissues of the oral cavity. The films include a water soluble film-forming polymer such as pullulan. Methods for producing the films are also disclosed.

Description

The thin film that comprises therapeutic agent

The cross reference of related application

According to 35 U.S.C. § 119, the series number that the application requires on July 1st, 2003 to submit to is 60/484, the series number that 009 U.S. Provisional Patent Application and on August 21st, 2003 submit to is 60/497, the rights and interests of 426 U.S. Provisional Patent Application, the content of described patent is included in by the mode of quoting at this.

Technical field

The present invention relates to comprise the therapeutic agent of nitroglycerin by digestible edible thin film.

Background technology

Nitroglycerin is powerful vasodilation, and it is by lax cardiovascular smooth muscle, and increasing the blood flow and the oxygen supply of cardiac muscle and reducing heart is that the pumping pressure that blood must be produced by systemic circulation prevents chest pain (angina pectoris).The reduction of this cardiac load has alleviated anginal pain.Except produce controlled hypotension in operation process, nitroglycerin is also in average of operation periods hypertension, or had the purposes of controlling blood pressure by the hypertension aspect that endotracheal intubation, anesthesia, incision of skin, the sternotomy, heart pass and post-operative recovery cause.

Existing nitroglycerin medication comprises: nitroglycerin pump spray, Nitroglycerin Sublingual, nitroglycerin slow releasing tablet, nitroglycerin transdermal patch, 2% nitroglycerin ointment and nitroglycerin intravenous drip.But all there is its inherent defective in described the whole bag of tricks.

Because oral administration is convenient, may be the most general method that gives nitroglycerin therefore.This does not generally have dangerous, painless and is easy to realize for most patient.Yet the oral administration of nitroglycerin is subjected to the puzzlement of some shortcomings.The particular problem relevant with the nitroglycerin slow releasing tablet of orally give compacting comprises fragility, content uniformity (for example weight and dose difference), nitroglycerin composition and the caused loss of efficacy to migration (migration), storage capsule and the container of other tablet.

Another problem with the pill oral administration is, the absorption rate that medicine enters blood flow after taking there are differences between the patient.The absorption of medicine depends on that medicine moves the secretory action of described organ, and the pH value that produces from stomach to small intestinal and large intestine in the harmonization of the stomach intestinal.Anxiety and anxiety can be slowed down mobile significantly and be reduced secretion, stop or reduce the final effect of medicine, and the onset of delay medicine.More of paramount importancely be between the time that the time and the medication effect of oral administration occurs, to have one section very long sluggishness usually.

Another shortcoming with the pill oral administration is that many medicines almost experience metabolism or deactivation at once.The vein of stomach and small intestinal and large intestine leads directly to liver.Therefore, the medicine that enters blood flow must at first pass through liver before being distributed to the systemic blood circulation.For most of medicine, (for some drugs, basically absolutely) eliminated from patient's blood flow when described " first by " liver more than 60 percent.As a result, for many medicines,, be unpractical especially with the pill oral administration for being used for the acting on for cardiovascular medicine of under CC situation quick acting.

For fear of some shortcoming of oral administration, often use injection.Intravenous nitroglycerin makes medicine enter patient's blood flow fast.In addition, such medicine of having avoided a large amount of of sending is eliminated by patient's liver.Therefore, be exposed to the total dose that is distributed to patient's body each several part before the liver with oral administration and compare, total dose that intravenous injection needs usually still less.But Most patients is also disliked injection, especially child and old people.In some patient, this dislike is so obvious, to such an extent as to the use of injection becomes serious misgivings.Because it is intensive physiological strains can aggravate patient's weak state, therefore sometimes, seriously ill or when suffering from weak property i or I, it is inappropriate adopting injection as the patient.

Another kind gives to comprise transdermal patch such as the method for therapeutic agents such as nitroglycerin.In this medication, give the potion nitroglycerin by entering blood flow by the cortex absorption.But the critical defect of transdermal patch method administration nitroglycerin is, when continuous use patch, the toleration of medicine can develop in 24 hours, the effectiveness of the reduction medicine that continues.Recommended to adopt following dosage regimen by the revision label of FDA approval, promptly alternately pasted medicine every day 12 to 14 hours, and have 10 to 12 hours time not paste medicine, this is quite consuming time and forget easily.And described patch can not be used in the position that hair, wound, scratch, callus is arranged on the health or scab, and can produce skin irritation in the place of using patch.

Some research worker have been advised and can have been given medicine through the buccal mucosa of cheek pouch or by sublingual administration.Referring to U.S. Patent No. 4,671,953, the full content of this patent is included in by the mode of quoting.The method that the mucosal tissue of this per os, pharynx and esophagus gives medicine has tangible effectiveness.Giving medicine by this approach can make medicine not be subjected to the effect of harmonization of the stomach intestinal digestion liquid.In addition, most of medicine has been avoided liver first by body the time, has therefore avoided extra metabolism of medicine and/or deactivation.

Generally speaking, all has undesirable taste by any said method administered agents.Therefore, in order to be organized in oral cavity or sublingual administration by the through port transmucosal, also need medicine is mixed in the comfortable material (mass) of certain type taste, for example in " confection " substrate.

For effectively using described medicine, confectionary products can contain equally distributed medicine everywhere, thereby guarantees the level unanimity of medicine.Perhaps, for some application, may wish that concentration changes in known and controlled scope, thereby change the speed of administration.Some difficulties when attempting, have been run into uniform way or other the mode hybrid solid medicine that can carefully control.Many medicines are insoluble in one or more hard sugar base material compositions or only part is solvable.Therefore, in the product that obtains, often find that medicine lacks even or controlled distribution.And also there are the relevant issues of moving between the nitroglycerin tablet in sublingual lozenge, and this is similar to the slow releasing tablet method that can produce high-caliber weight and DM between tablet.

In addition, many existing pastille lozenges are easy to cracked when placing mouth.Therefore, medicine can't discharge into mucosal tissue by homogeneous.More properly, cracked lozenge major part is chewed and is swallowed, and described medicine enters blood flow by above-mentioned by the harmonization of the stomach intestinal.So, will be appreciated that for for giving by oral mucosas tissue in the medicine to use, lozenge has the limitation of determining very much.Therefore, lozenge is not used to give potent, active remedy, for example acts on the medicine of central nervous system, cardiovascular system or kidney vascular system.

Shown hope although give some drugs, for the medicine of producing desired form and give to develop complete acceptable method and but also be difficult to realize for this medicine by oral mucosas tissue.

If there is suitable method and composition in each patient, to provide accurate dose to reach definite effect, will be that orally give is potent, the major progress in active remedy field so.If method and composition can be provided, needn't then will be the another progress in this field with mixture heated to degrading medicine (comprising insoluble drugs) is evenly mixed in the dissolvable matrix.

Therefore, need a kind of improved carrier that is better than existing goods, to give such as therapeutic agents such as nitroglycerin.

Summary of the invention

But the invention provides physiologically acceptable edible or digestible film, described thin film be particluarly suitable for the patient the mouth in fast the dissolving.In one embodiment of the invention, described thin film comprises nitroglycerin.In another embodiment, described thin film comprises nitroglycerin and at least a other forms of pharmacologically active agents.

In another embodiment of the invention, but described edible or digestible film comprise the combination of therapeutic agent or two or more therapeutic agents, and wherein said therapeutic agent includes but not limited to have the medicament of following purposes: antimicrobial, NSAID (non-steroidal anti-inflammatory drug), anti-inflammatory agent, cough medicine, decongestant, antihistaminic, expectorant, diarrhea, the H2-antagonist, proton pump inhibitor, the non-selective central nervous system depressant of whole body, the non-selective central nervous system stimulant of whole body, the medicine of selectively changing central nervous system function, antiparkinsonism drug, narcosis analgesic, antipyretic analgesic, the psychopharmacology medicine, resisting hypertension and cardiovascular treatment agent, Dermatological Agents, glucocorticoids and steroidal compounds, anti-malarial agents and antiparasitic, antifungal, the periodontitis agent, emetic, the therapeutic agent of gout, glaucomatous therapeutic agent, the therapeutic agent of scatterbrained hyperactivity disorder, the pretreat and the therapeutic agent of contact chemical weapons, the therapeutic agent of acute roentgenization, opioid analgesics, hemorrhage, the syndromic therapeutic agent of Sj rgren ' s, the smoking cessation agent.

The invention still further relates to the method soft, that self do not adhere to, especially be fit to the thin film of oral delivery nitroglycerin of producing.Described method comprises at least a film former and aqueous solution, to form hydrated polymer gel; This hydrated polymer gel is cast on the substrate; And the gel that makes casting solidifies to form thin film.In another embodiment, before forming described hydrated polymer gel, in one or more compositions with nitroglycerin or other therapeutic agent or medicament adding mixture.

The specific embodiment

Should be understood that the present invention is not limited to the described concrete grammar of this description, rules, reagent etc., because these all can change.It is to be further understood that the employed term of this description just in order to describe specific embodiment, and do not intend limiting the scope of the invention.Must be noted that, this description and in appended embodiment " one " " a kind of " and " being somebody's turn to do " of employed singulative comprise that plural number refers to, unless context clearly indicates in addition.

Unless otherwise defined, otherwise the implication of employed all technology of this description and scientific terminology and common understand identical of those skilled in the art.Preferable methods, system component and material are described, although in enforcement of the present invention or test, can use and the method described in this manual and materials similar or any method and the material that are equal to.All reference materials cited herein are all intactly included at this by the mode of quoting.

Whole publications and patent that this description is mentioned are all included in by the mode of quoting at this, with narration and open, for example, system component and the method that can use in conjunction with the present invention described in above-mentioned publication.The publication that provides this description to discuss is only openly submitted day to early than the application because of it.Any content of this description all can not be interpreted as, and the right of admitting the inventor is no earlier than open day of described publication, and the inventor may have this right because of invention formerly or other reasons.

But the present invention relates to the compositions of oral solubilized, edible or digestible film and the manufacture method of this thin film, described thin film can be used as by including but not limited to: the carrier of oral mucosas tissue's Noninvasive administration nitroglycerin of mouth, pharynx and esophagus.But the invention still further relates to the compositions of oral solubilized, edible or digestible film and the manufacture method of this thin film, described thin film can be used as by including but not limited to: the carrier of the various therapeutic agents of oral mucosas tissue's Noninvasive administration (can comprise or not comprise nitroglycerin in thin film) of mouth, pharynx and esophagus.

One embodiment of the invention are the acceptable thin film of physiology, described thin film is particluarly suitable for the orally-dissolvable to send the nitroglycerin medicament that can be used as effective tool in treatment or prevent disease or disease of patient, described disease or disease include but not limited to angina pectoris, ventricular arrhythmia, supraventricular arrhythmia and other cardiovascular disorder and disease, or any other can be with the disease or the disease of nitroglycerin treatment.Described thin film can comprise any edible or digestible polymer or film former and nitroglycerin.

In another embodiment of the invention, but described edible or digestible film comprise the combination of a kind of therapeutic agent or two or more therapeutic agents, and wherein said therapeutic agent includes but not limited to have the medicament of following purposes: antimicrobial, NSAID (non-steroidal anti-inflammatory drug), anti-inflammatory agent, cough medicine, decongestant, antihistaminic, expectorant, diarrhea, the H2-antagonist, proton pump inhibitor, the non-selective central nervous system depressant of whole body, the non-selective central nervous system stimulant of whole body, the medicine of selectively changing central nervous system function, antiparkinsonism drug, narcosis analgesic, antipyretic analgesic, the psychopharmacology medicine, resisting hypertension and cardiovascular treatment agent, Dermatological Agents, glucocorticoids and steroidal compounds, anti-malarial agents and antiparasitic, antifungal, the periodontitis agent, emetic, the therapeutic agent of gout, glaucomatous therapeutic agent, the therapeutic agent of scatterbrained hyperactivity disorder, the pretreat and the therapeutic agent of contact chemical weapons, the therapeutic agent of acute roentgenization, opioid analgesics, hemorrhage, syndromic therapeutic agent of Sj rgren ' s and smoking cessation agent.Described thin film can also comprise or not comprise nitroglycerin.

Authorize people's such as Ozaki (Hayashibara) U.S. Patent No. 5,518,902 disclose high-load amylopectin (pullulan) product, edible film, dentifrice and medicine (the 3rd hurdle for example, capable and the Embodiment B-8 of 44-56), the full content of described patent is included in by the mode of quoting at this.Described product can also comprise various components except that amylopectin, for example other polysaccharide, polyhydric alcohol, antiseptic and flavoring agent (the 4th hurdle, the 58th walks to the 5th hurdle, the 11st row).

The U.S. Patent No. 5,411,945 of authorizing people such as Ozaki (Hayashibara) discloses the amylopectin bonding agent and by the product of its production, has comprised edible film (Embodiment B-2), and the full content of described patent is included in by the mode of quoting at this.Described product can also comprise various components except that amylopectin, for example other polysaccharide, antibacterial, flavoring agent and pharmaceutically active substances (the 4th hurdle, 5-15 is capable).

The U.S. Patent No. 4,851,394 of authorizing Kubodera discloses the edible film of glucomannan/polyhydric alcohol, described thin film can comprise amylopectin (the 3rd hurdle, the 59th walks to the 4th hurdle, the 21st row), the full content of described patent is included in by the mode of quoting at this.Described thin film and existing amylopectin based thin film (allegedly lacking water resistance (the 1st hurdle, 40-44 is capable)) differ widely.

People's such as Hijiya U.S. Patent No. 3,784,390 discloses the amylopectin thin film and in the coating of food and medicine and the application in packaging material and other oxygen-sensitive material, the full content of described patent is included in by the mode of quoting at this.All embodiment of this patent all are taught in and mix amylopectin in the hot water.

People's such as Nakamura U.S. Patent No. 4,623,394 discloses the mechanograph that can progressively decompose, and described goods can be the thin film made from amylopectin, and the full content of described patent is included in by the mode of quoting at this.These goods contain a kind of special different mannan, and this different mannan can be a carob gum.

People's such as Hijiya U.S. Patent No. 4,562,020 discloses the production method of a kind of self-supporting glucosan (can be amylopectin) thin film, and the full content of described patent is included in by the mode of quoting at this.

The U.S. Patent No. 5,569,482 of authorizing people such as Naga discloses the method for being made edible protein film by the soybean protein in various sources, and the full content of described patent is included in by the mode of quoting at this.

The U.S. Patent No. 5,288,497 of authorizing people such as Stanley disclose produce and give can through port, the lipotropy that absorbs of the mucosal tissue of pharynx and esophagus and the method for non-lipophilic drugs, the full content of described patent is included in by the mode of quoting at this.

Authorize Fuisz Technologies, the U.S. Patent No. 6,020 of Ltd, 002 discloses based on the compositions of shearing the substrate that is shaped, described compositions can be made tablet (7 hurdles, the 4th hurdle to the, the 47th row), and the full content of described patent is included in by the mode of quoting at this.Described substrate adopts the disclosed THE ADIABATIC SHEAR IN of this description (flash-shear) method to be shaped.The disclosed substrate of the not mentioned employing of this patent is produced thin film, and disclosed substrate needs heating.

The U.S. Patent No. 6,337,082 of authorizing people such as Fuisz discloses the substrate that can be used in delivering therapeutic agents and make food, and the full content of described patent is included in by the mode of quoting at this.

WO 03/011259 discloses the edible maltodextrin thin film that is used for being discharged in the oral cavity, and the full content of described patent is included in by the mode of quoting at this.

WO 03/043659 discloses the edible film that contains the hydrocolloid film former, and described thin film decomposes to discharge activating agent rapidly when placing mouth, and the full content of described patent is included in by the mode of quoting at this.

WO 02/43657 discloses edible film compositions and the manufacture method thereof that does not contain amylopectin, and the full content of described patent is included in by the mode of quoting at this.

WO 02/02645 discloses the method that adopts cold-water-soluble beta glucan to produce gel, and described gel can be used for comprising the multiple use that forms edible film, and the full content of described patent is included in by the mode of quoting at this.

WO 99/17753 discloses rapid dissolved thin film, and this thin film is used for sending the medicine that plan absorbs in digestive tract, and the full content of described patent is included in by the mode of quoting at this.

WO 98/26780 discloses and has been used for using also platypelloid type, foil-type, paper mold or the sheet type outer package (presentation) of release of active agent in the oral cavity, and the full content of described patent is included in by the mode of quoting at this.Disclosed concrete active component is a buprenorphine among the WO 98/26780.

WO 98/20862 discloses and has been used for the thin film oral cavity, that can comprise beauty treatment or active medicinal matter, and the full content of described patent is included in by the mode of quoting at this.

Series number is that the U. S. application of No.2003/0107149 discloses and makes the method for intending being used for the thin film that oral drugs send, and the full content of described patent includes in by the mode of quoting at this.The not mentioned nitroglycerin of sending of this application.

WO 98/26763 discloses and has been used for active substance is discharged into flat sample, paillon foil sample, pattern or sheet-like outer package in the oral cavity, and the full content of described patent is included in by the mode of quoting at this.Concrete disclosed active substance is an apomorphine.

But series number be No.2003/00080008 U.S. Patent Application Publication have the digestible film of high concentration antimicrobial and essential oil, the full content of described patent is included in by the mode of quoting at this.

Series number be No.2003/0035841 U.S. Patent Application Publication be used for the edible film in oral cavity, except that amylopectin, described thin film contains at least three types film former, comprise maltodextrin, hydrocolloid and filler, the full content of described patent is included in by the mode of quoting at this.

But although there has been quick-dissolving oral cavity digestible film in the prior art, still there is room for improvement in this class thin film and preparation method thereof, especially is used for sending this class thin film of nitroglycerin.

The nitroglycerin of this description indication is also referred to as three nitric acid-1,2, the 3-glycerine ester, glycerol trintrate, glyceryl trinitrate, nitroglycerin, glyceryl trinitrate, nitroglycerine, trinitin, blasting gelatine, explosive oil and S.N.G., and known with multiple commercial trade (brand) name, include but not limited to Adesitrin, Angibid, Angiolingual, Anginine, Angorin, Aquo-Trinitrosan, Cardamist, Coro-Nitro, Corditrine, Deponit, Diafusor, Gilucor " nitro ", GTN, Klavikordal, Lenitral, Lentonitrina, Millithrol, Minitran, Myoglycerin, Niong, Nitradisc, Nitran, Nitriderm, Nitro-Bid, Nitrobon, Nitrocap, Nitrocap TD, Nitrocine, Nitrocontin, Nitroderm TTS, Nitrodisc, Nitro-Dur, Nitrofortin, Nitro-Gesanit, Nitroglin, Nitroglyn, Nitroguard, Nitrol, Nitrolan, Nitrolande, Nitrolar, Nitro-lent, Nitrolin, Nitrolingual, Nitro Mack, Nitromel, Nitromin, Nitron, Nitronal, Nitronet, Nitrong, Nitro-Pflaster-ratiopharm, NitroPRN, Nitroquick, Nitrorectal, Nitroretard, Nitrosigma, Nitrospan, Nitrostat, Nitrotab, Nitro-Time, Nitrozell retard, Notrong, Nysconitrine, organic nitrate, organic nitrite, Percutol, Perlinganit, Perglottal, Reminitrol, Suscard, Sustac, Sustonit, Transderm-Nitro, Transiderm-Nitro, Tridil, Trinalgon, Trinitrosan and Vasoglyn.

Can buy special from many companies at medicinal nitroglycerin, include but not limited to 3MPharmaceuticals, Abbott Labs, Aventis Pharmaceuticals, BaxterHealthcare, Cellegy Pharmaceuticals, Inc., DuPont-MerckPharmaceutical Co., F.Hoffman La-Roche, Ltd., ForestLaboratories, Inc., GlaxoSmithKline, Hoechst Marion Roussel, Kenwood Laboratories, Key Pharmaceuticals, MedleyPharmaceuticals, Merck ﹠amp; Co, Inc., Novartis Pharma AG, Parke-Davis, Pfizer, G.Pohl-Boskamp GmbH ﹠amp; Co., Rhone-PouleneRorer Pharmaceutical, Inc., Schwartz Pharma AG, Solvay Pharma, Vortech Pharmaceuticals and Warner Lambert Company.

Pure nitroglycerin is high explosives, must handle extremely carefully.The nitroglycerin crystal of stable form melts in the warm area of 55.4 (13 ℃), and extremely unstable when melting; If place high temperature or clashed into, liquid nitroglycerin can explode.Therefore, after the explosivity of nitroglycerin is controlled (usually by chemical compound is distributed in the inert substance), be only the most useful.Before making edible film of the present invention, commercially available nitroglycerin can be diluted to concentration to be about 90% weight, about 80% weight, about 70% weight, about 60% weight, about 50% weight, about 40% weight, about 30% weight, about 20% weight, about 10% weight, about 9% weight, about 8% weight, about 7% weight, about 6% weight, about 5% weight, about 4% weight, about 3% weight, about 2% weight, about 1% weight or to be lower than about 1% weight.In one embodiment, before being used for the inventive method manufacturing edible film, nitroglycerin can be diluted to concentration and be lower than 2% weight.In addition, in the present invention, when treatment of nitric acid glycerol, recommend to dress the medicated clothing of some protectiveness, for example robe, respiratory organ, glove and protective eye lens are to avoid its toxic action.Because skin and mucosa are easy to absorb nitroglycerin, therefore must avoid direct contact skin.Nitroglycerin absorbs rapidly by skin and makes it become the anginal beneficial drugs of treatment, but this may be deleterious for myocardium anoxybiotic healthy individual not occurring.

Nitroglycerin can prepare and in aqueous form in U.S. Patent No. 4,879, narration to some extent in 308, whole disclosures of described patent are included in by the mode of quoting at this, and all right nonpolar liquid form preparation of nitroglycerin, as U.S. Patent No. 5,869, described in 082, whole disclosures of described patent are included in by the mode of quoting at this.

The composition of thin film

But one embodiment of the invention are the instant films that comprise the nitroglycerin of physiology receiving amount.The nitroglycerin of wording as used herein " physiology can be accepted " amount is intended to comprise that the amount or the dosage that give the patient are enough to tolerate, and effectively and not causes bad side effect to treating, and be physiology acceptable and with oral thin film be compatible.According to the present invention, can be used in the amount of the nitroglycerin in the instant film, depend on the required dosage of nitroglycerin that effective dose is provided.The same with the narration to nitroglycerin herein, but any other intended the physiology receiving amount of the therapeutic agent of allotment in thin film of the present invention, can determine in a similar fashion.

The nitroglycerin or the required dosage of any other therapeutic agent of effective dose are provided, are easy to adopt known technology to determine, and normally can impel the amount of symptom or amelioration of disease by those of ordinary skill in the art.Concrete dosage can be adjusted according to the situation of disease, patient's age, body weight, general health situation, sex, diet, spacing of doses, discharge rate and with the coupling of other medicines.The treatment effective dose of nitroglycerin as used herein, for about 0.001mg to about 1000mg, perhaps about 0.01mg is to about 100mg, perhaps about 0.05mg is about 50mg extremely, perhaps about 0.1mg is the amount of about 40mg extremely.

The preparation of thin film

In one embodiment, the present invention comprises the thin film of nitroglycerin or the thin film that the present invention comprises any other therapeutic agent, comprise at least a film former, and may further include water, other film former, triglyceride, antiseptic, the poly(ethylene oxide) chemical compound, propylene glycol, synergist, saliva stimulant, plasticizer, coolant, surfactant, the nitroglycerin stabilizing agent, membrane stabilizer, emulsifying agent, thickening agent, binding agent, buffer agent, releasing agent, penetration enhancer, sweeting agent, other natural and artificial flavors, coloring agent, the coating dress material, other forms of pharmacologically active agents, antibacterial, antiviral agent, other therapeutic agent or the like.

The described film former that is used for thin film according to the present invention can be any suitable film former, includes but not limited to: amylopectin, hydrocolloid, beta glucan, maltodextrin, comprise hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methylcellulose, hydroxy methocel, hydroxyethyl-cellulose is at interior cellulose, polyvinylpyrrolidone, polyvinyl alcohol, sodium alginate, Polyethylene Glycol, ethyl cellulose, Cellulose ethyl hydroxypropyl ether, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, such as carob gum, carrageenin, xanthan gum, Tragacanth, guar gum, acacia gum, arabic gum, karaya, the natural gum that rolls, the natural gum of tamarind gum, polyacrylic acid, the methylmethacrylate copolymer, carboxy vinyl polymer, amylose, high amylose starches, the hydroxypropylation high amylose starches, dextrin, pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, zein, baregin, soy protein isolate, lactalbumin isolate, casein and composition thereof.The film former that is used for thin film can also comprise: biodegradable polymer, copolymer, block polymer, described material includes but not limited to: polyglycolic acid (PGA), polylactic acid (PLA) Ju diox (polydioxanoe), poly-oxalate, poly-α ester, polyanhydride, poly-acetate, polycaprolactone, poe, polyamino acid, poly-amino-carbon acid esters, polyurethane, Merlon, polyamide, Polyalkylcyanoacrylanano, the space polymers of L-and D-lactic acid (stereopolymer), two (right-the carboxylic phenoxy group) propanoic acid and decanedioic acid copolymer, the decanedioic acid copolymer, caprolactone copolymer, polylactic acid/polyglycolic acid/ethylene glycol copolymer, polyurethane and copolymer of poly lactic acid, polyurethane and copolymer of poly lactic acid, the alpha amino acid copolymer, alpha amino acid and caproic acid copolymer, α-benzyl glutamic acid and ethylene glycol copolymer, succinate and ethylene glycol copolymer, poly phosphazene, polyhydroxy-alkanoates and any combination thereof.

In one embodiment of the invention, at least a film former is an amylopectin, content be thin film about 0.01 to about 99wt%, about 30 to about 80wt%, or about 45 to about 70wt%, or about 60 to about 65wt%.

In one embodiment of the invention, at least a film former is its filming performance hydrocolloid material of dawn known in the art.Described hydrocolloid material can broad concentration range exist, include but not limited to about 50 to about 90wt%, or about 50 to about 80wt%.

In one embodiment of the invention, at least a film former is a maltodextrin.Described maltodextrin can broad concentration range exist, include but not limited to about 5 to about 60wt%, preferably between about 20 to about 40wt%, and can exist with hydrocolloid material, content be thin film about 10 to about 50wt%, or about 30 to about 40wt%.

In one embodiment of the invention, at least a film former is the beta glucan solution of purification.Described beta glucan solution can use in the concentration range of broad, includes but not limited to: about 10wt% of thin film.

Comprise the thin film of nitroglycerin, or comprise the thin film of any other therapeutic agent, also can comprise triglyceride.The example of triglyceride includes but not limited to: vegetable oil, for example Semen Maydis oil, Oleum Helianthi, Oleum Arachidis hypogaeae semen, olive oil, Semen Brassicae Campestris oil, soybean oil and composition thereof.In one embodiment, described triglyceride is an olive oil.Described triglyceride add to amount in the thin film be about 0.1wt% of thin film to about 12wt%, or about 0.5 to about 9wt%.

Comprise the thin film of nitroglycerin, or comprise the thin film of any other therapeutic agent, can also comprise antiseptic.About 0.001wt% that the addition of described antiseptic can be thin film is to about 5wt%, or about 0.01 to about 1wt%.In one embodiment, antiseptic comprises sodium benzoate and potassium sorbate.

Comprise the thin film of nitroglycerin, or comprise the thin film of any other therapeutic agent, can also comprise the poly(ethylene oxide) chemical compound.The molecular weight of described poly(ethylene oxide) chemical compound can include but not limited in the scope of non-constant width: from about 50,000 to about 6,000,000.In one embodiment, the N-10 of described poly(ethylene oxide) chemical compound for buying from Union Carbide Corporation.About 0.1wt% that the addition of described poly(ethylene oxide) chemical compound can be thin film is to about 5wt%, or about 0.2 to about 4.0wt%.

Comprise the thin film of nitroglycerin, or comprise the thin film of any other therapeutic agent, can also comprise propylene glycol.The amount of described propylene glycol in can relative broad range added, and includes but not limited to: from about 1wt% of thin film about 20wt% extremely, or about 5 to about 15wt%.

The thin film that comprises nitroglycerin can also comprise the nitroglycerin synergist.This class nitroglycerin synergist includes but not limited to: U.S. Patent No. 6,559, and 180 disclosed menthols, the full content of described patent is included in by the mode of quoting at this.According to the therapeutic agent in the thin film, can add the synergist of any other therapeutic agent of allotment in thin film of the present invention.

Comprise the thin film of nitroglycerin, or comprise the thin film of any other therapeutic agent, can also comprise saliva stimulant.Useful saliva stimulant includes but not limited to: U.S. Patent No. 4,820, and disclosed saliva stimulant in 506, the full content of described patent is included in by the mode of quoting at this.Saliva stimulant comprises food acids, for example, and citric acid, lactic acid, malic acid, succinic acid, ascorbic acid, adipic acid, fumaric acid and tartaric acid.Suitable food acids includes but not limited to citric acid, malic acid and ascorbic acid.The amount of saliva stimulant can be used in the scope of broad in the thin film, includes but not limited to: from about 0.01 to about 12wt%, or from about 1 to about 10wt%, or from about 2.5 to about 6wt%.

Can be to the thin film that comprises nitroglycerin, or comprise in the thin film of any other therapeutic agent and add the plasticizer that includes but not limited to glyceryl triacetate, wider range of addition includes but not limited to: from about 0 to about 20wt%, or from about 1 to about 2wt%.Other suitable manufacturing methods includes but not limited to polyhydric alcohol, for example sorbitol, glycerol, Polyethylene Glycol, propylene glycol, hydrogenated starch hydrolysates, corn syrup and monoacetin, diacetin, maltose alcohol and mannitol.

Can be to the thin film that comprises nitroglycerin, or comprise and add the coolant that includes but not limited to thin lotus succinate in the thin film of any other therapeutic agent, wider range of addition includes but not limited to: from about 0.001 to about 2.0wt%, or from about 0.2 to about 0.4wt%.The coolant that comprises thin lotus succinate is from Mane, and Inc. buys.Other suitable coolant includes but not limited to: WS3, WS23, Ultracool II or the like.

Can be to the thin film that comprises nitroglycerin, or comprise and add the surfactant that includes but not limited to glycerine monofatty ester, fatty acid two glyceride and polyoxyethylene sorbitan ester, for example Atmos 300 and Polysorbate 80 in the thin film of any other therapeutic agent.Described surfactant can add in the scope of broad, includes but not limited to: thin film about 0.5 to about 15wt%, or about 1 to about 5wt%.Other suitable surfactant comprises but is not limited to: Pluronic acid (pluronic acid), sodium laurylsulfate or the like.

The described thin film that comprises nitroglycerin can also comprise the nitroglycerin stabilizing agent in thin film.The existence of stabilizing agent has reduced the loss of nitroglycerin in the thin film in the thin film, and can prolong the pot-life.Suitable nitroglycerin stabilizing agent dawn known in the art, and described stabilizing agent comprises but is not limited to U.S. Patent No. 6,500, the glyceryl monostearate described in 456, and the full content of described patent is included in by the mode of quoting at this.According to the therapeutic agent in the thin film, can add the stabilizing agent of any other therapeutic agent of allotment in thin film of the present invention.

The thin film stabilizing agent that can add in the thin film that comprises nitroglycerin comprises but is not limited to xanthan gum, carob gum and carrageenin that wider range of addition includes but not limited to: from about 0 to about 10wt%, or from about 0.1 to about 2wt%.Other suitable stabilizers includes but not limited to guar gum or the like.

Can be to the thin film that comprises nitroglycerin, or comprise the emulsifying agent that adds in the thin film of any other therapeutic agent and comprise but be not limited to: lecithin, bentonite, aluminium-magnesium silicate (veegum), stearate, triethanolamine stearate, the ester derivant of stearate, cetylate, the ester derivant of cetylate, oleate, the ester derivant of oleate, glyceride, the ester derivant of glyceride, Olestra, polyglycerin ester, animal wax, vegetable wax, synthetic wax, oil, quaternary ammonium compounds, Acacia farnesiana Willd., gelatin or the like, wider range of addition, include but not limited to: from thin film about 0 to about 5wt%, or from about 0.01 to about 0.7wt%.

Can be to the thin film that comprises nitroglycerin, or comprise the thickening agent that adds in the thin film of any other therapeutic agent and include but not limited to cellulose ethers, for example methylcellulose, carboxymethyl cellulose or the like, wider range of addition, include but not limited to: from thin film about 0 to about 20wt%, or from about 0.01 to about 5wt%.

Can be to the thin film that comprises nitroglycerin, or comprise the binding agent that adds in the thin film of any other therapeutic agent and include but not limited to starch, wider range of addition includes but not limited to: from thin film about 0 to about 10wt%, or from about 0.01 to about 2wt%.

Comprise the thin film of nitroglycerin, or comprise in the thin film of any other therapeutic agent and can comprise suitable sweeting agent, described sweeting agent comprises natural and sweeting agent known in the art artificial sweetening agent.Suitable sweeting agent comprises but is not limited to:

A. water-soluble sweetening agent, for example monosaccharide, disaccharidase and polysaccharide are such as starch, corn-syrup solids, dihydrochalcone, monellin, stevioside and the glycyrrhizin of xylose, ribose, glucose (dextrose), mannose, galactose, fructose (levulose), sucrose (sugar), maltose, Nulomoline (fructose that is produced by sucrose and the mixture of glucose), partial hydrolysis;

B. water solublity artificial sweetening agent, for example soluble sugar refined salt is the sodium salt of glucide or calcium salt, cyclamate, 3,4-dihydro-6-methyl isophthalic acid, 2,3-Evil thiazine-4-ketone-2, the sodium salt of 2-dioxide, ammonium salt or calcium salt, 3,4-dihydro-6-methyl isophthalic acid, 2,3-Evil thiazine-4-ketone-2, the potassium salt of 2-dioxide (glucide of acesulfame-K), free acid form or the like;

C. based on the sweeting agent of dipeptides, the aspartate-derived sweeting agent of L-for example, such as L-aspartyl-L-phenylalanine methyl ester (aspartame) and in U.S. Patent No. 3,492, material described in 131, described patent is included in by the mode of quoting at this, L-α-aspartoyl-N-(2,2,4,4-tetramethyl-3-vulcanizes trimethylene (thietanyl))-D-aminopropanamide hydrate, L-aspartoyl-L-phenyl glycerine and L-aspartoyl-L-2, the methyl ester of 5-dihydro phenyl-glycine, L-aspartoyl-2,5-dihydro-L-phenylalanine, L-aspartoyl-L-(1-cyclohexylidene (cyclohexyen))-alanine or the like;

D. the deutero-water-soluble sweetening agent of naturally occurring water-soluble sweetening agent, the chlorinated derivatives of for example common sugar (sucrose), the chlorinated derivatives of for example known product sucralose by name, and

E. based on proteinic sweeting agent, kiwi fruit element (thaumatoccous danielli) (thaumatin I and II) for example.

Generally speaking, use the auxiliary sweeting agent of effective dose to provide concrete compositions required sugariness, and described amount can change according to selected sweeting agent.When sweeting agent that use is easy to extract, described amount is generally 0.01 weight % of compositions to about 10 weight %.The common use amount of water-soluble sweetening agent described in the top category-A is about 0.01% to about 10wt%, and preferred about 2 to about 5wt%.Owing to the sweet characteristic that increases of known sweeting agent, so some sweeting agent in the category-A (for example glycyrrhizin) can adopt the amount of following B-E class suggestion use.On the contrary, generally with about 0.01 to about 10wt%, or about 2 to about 8wt% at the described sweeting agent of B-E apoplexy due to endogenous wind, or about amount of 3 to about 6wt% is used.Described amount can be used for obtaining required sugariness, and this sugariness is irrelevant with the taste level (flavor level) that obtains from employed any optional flavored oils.

Can carry out coating to the thin film that is used in the nitroglycerin in the thin film or comprises any other therapeutic agent, covering the taste of nitroglycerin or other therapeutic agent, or prevent nitroglycerin or other therapeutic agent paralysis or influence other top layer in tongue or the oral cavity.The coating that can use is known to those skilled in the art.Described coating includes but not limited to such as the polymer of Eudragit  E, such as cellulosics of ethyl cellulose or the like.Other approach of covering nitroglycerin or other therapeutic agent taste also comprises by making spent ion exchange resin, the AmberliteRP-69 that buys from Rohm and Haas for example, and the Dow XYS-40010.00 that buys from Dow Chemical Co.

Other natural can being selected from artificial flavors is synthesized flavored oils and seasoning aromatic, and/or comes from oil, oleo-resins and the extract of plant, leaf, flower, fruit etc. and combination thereof.Typical flavored oils includes but not limited to: Oleum menthae, Oleum Cinnamomi, Fructus Piperis peppermint oil, Oleum Caryophylli, laurel oil, Oleum thymi vulgaris, Cedar leaf oil, Semen Myristicae oil, sage oil and Semen Armeniacae Amarum oil.Manually, natural or synthetic fruit flavors also is useful, for example Rhizoma et radix valerianae, chocolate, coffee, cocoa and Fructus Citri Limoniae oil, comprise Fructus Citri Limoniae, Citrus, Fructus Vitis viniferae, Lay lemon and grapefruit, and the fruit elite that comprises Fructus Mali pumilae, pears, peach, Fructus Fragariae Ananssae, rasp berry, Fructus Pruni pseudocerasi, Fructus Armeniacae Mume, Fructus Ananadis comosi, Fructus Pruni or the like.Described flavoring agent can be used alone or as a mixture.Normally used flavoring agent comprises Herba Menthae, artificial vanilla, cinnamon derivative and the various fruit flavors such as Mentha arvensis L. syn.M.haplocalyxBrig, and described flavoring agent can be used alone or as a mixture.The flavoring agent of aldehydes and esters be can also use, cinnamyl acetate, cinnamic aldehyde, citral, acetal, acetic acid dihydro Pueraria lobota thread ester, eugenyl formic acid esters, p-methyl anisole or the like comprised.Generally speaking, can use any flavoring agent or food additive, for example at Chemicals Usedin Food Processing, National Academy of Sciences publishes (1274), the flavoring agent described in the 63-258 page or leaf.More aldehydes flavoring agent example includes but not limited to: acetaldehyde (Fructus Mali pumilae), benzaldehyde (Fructus Pruni pseudocerasi, Semen Armeniacae Amarum), cinnamic aldehyde (Cortex Cinnamomi), citral, it is α-citral (Fructus Citri Limoniae, the Lay lemon), neral, be neral (Fructus Citri Limoniae, Lay lemon), n-capric aldehyde (Citrus, Fructus Citri Limoniae), ethyl vanillin (Rhizoma et radix valerianae, butter), heliotropin, it is heliotropine (Rhizoma et radix valerianae, butter), vanillin (Rhizoma et radix valerianae, butter), jasminal (pungent fruital flavor), butyraldehyde (butter, cheese), valeral (butter, cheese), citronellal (polytype regulator), n-capric aldehyde (citrus fruit), the aldehyde of C-8 (citrus fruit), the aldehyde of C-9 (citrus fruit), the aldehyde of C-12 (citrus fruit), 2-ethyl butyraldehyde (berry fruits), hexenoic aldehyde, promptly trans-2 (berry fruits), tolyl aldehyde (Fructus Pruni pseudocerasi, Semen Armeniacae Amarum), 3,4-dimethoxybenzenecarbonal (Rhizoma et radix valerianae), 2,6-dimethyl-5-heptenal, be melonal (Fructus Melo), 2,6-dimethyl octanal (unripe fruit) and 2-olefine aldehydr (Citrus, Fructus Citri tangerinae), Fructus Pruni pseudocerasi, Fructus Vitis viniferae, and composition thereof or the like.

Be used in the thin film that comprises nitroglycerin or comprise the amount of the flavoring agent in the thin film of any other therapeutic agent, usually just to for example preference problem of factors such as fragrance type, individual taste and desired concn.Therefore, in order to obtain the required effect of final products, described amount can change.This change is within those skilled in the art's the limit of power, and does not need more experiment.Generally speaking, can use about 0.1 to about 30wt%, 2 to about 25wt%, 8 to about 10wt% amount.

Comprise the thin film of nitroglycerin among the present invention, or the thin film that comprises any other therapeutic agent can also comprise coloring agent or stain.Described coloring agent can effectively produce the amount of required color and use.Useful coloring agent comprises the pigment such as titanium dioxide among the present invention, and the amount of about 5wt% is mixed at the most, and preferably is lower than about 1wt%.Coloring agent can also comprise that natural food colour and being suitable for eats, the dyestuff of medicinal and beauty treatment usefulness.Described coloring agent is called as FD﹠amp; C dyestuff and color lake.Acceptable raw material is preferably water miscible in the above-mentioned application, and comprises FD﹠amp; C Blue No.2, promptly 5, the disodium salt of 5-indigo disulfonic acid.Similarly, the dyestuff that is called as Green No.3 comprises kiton colors, i.e. 4-[4-N-ethyl-right-sulfo-benzylamino) diphenyl-methylene]-single sodium salt of [1-N-ethyl-N-is to the sulfonium benzyl)-2,5-ring-hexadiene imines].FD﹠amp; C and D﹠amp; The complete description of C dyestuff and corresponding chemical constitution thereof can be at Kirk-Othmer Encyclopediaof Chemical Technology, the 5th volume, and the 857-884 page or leaf finds, and its original text is included in by the mode of quoting at this.

In order to prepare the required nitroglycerin that comprises dissolvable matrix (in order to form a kind of dosage form) or also to comprise the thin film of any other therapeutic agent, may be necessary in conjunction with the component of some general types.Described component includes but not limited to, is used for preparing kinds of ingredients, nitroglycerin and other required chemical active ingredient, for example buffer agent, penetration enhancer, other forms of pharmacologically active agents or the like of conventional confection.

Included component type can be classified as following classification usually, includes but not limited to:

1) flavoring agent,

2) sweeting agent,

3) flavour enhancer,

4) releasing agent,

5) buffer agent,

6) one or more therapeutic agents,

7) dissolvable matrix raw material, and

8) penetration enhancer

Described component can be a liquid releasable or that can slowly discharge.

As mentioned above, described component can be respectively can promoting blended form to provide, for example exsiccant powder.Help the combination of composition like this, in addition insoluble or when chemically incompatible at composition.All or some initial compositions or non-active ingredient can be the compositions (" being commonly referred to be safe ") in the GRAS table.

In some drugs, may also need to add lubricant from mould, to take out dosage form.This class preparation can also produce water proofing property to a certain degree.As mentioned above, can be by the compression degree of described compositions, Chemical Control or the dissolution rate of physics control dosage form in patient's mouth.Described lubricant or releasing agent can include but not limited to, such as materials such as compritol 888 (glyceryl behenate), calcium stearate and sodium stearates.Described reagent can promote stripping as required or can suppress stripping.

Mixture of powders enters in the embodiment of skewed slot through funnel in process of production, and lubricant also is useful.Lubricant and surfactant can promote product to flow and can avoid forming electrostatic charge in the preparation, and the formation of electrostatic charge can cause that described composition separates because of electrostatic force.

Also may need to comprise buffer agent in the described compositions.The thin film that buffer agent can make the thin film that comprises nitroglycerin or comprise any other therapeutic agent can be in mouth in the favourable pH environment, so that the mucosal tissue of its through port, pharynx and esophagus.The buffer agent that mixes in the compositions can be used for influencing the change of saliva of buccal cavity environment pH, thereby helps being easier to the nitroglycerin of the unionized form by mucosal tissue or the existence of other active component or medicine.

In addition, suitable pH regulator can help to produce the better to eat product that comprises nitroglycerin or other medicines, and described nitroglycerin or other medicines have stronger acidity (and therefore tart flavour arranged) or stronger alkalescence (and therefore bitterness is arranged).Therefore, will add in the dissolvable matrix such as the buffer system of citric acid/sodium citrate and may need.Also can use phosphate buffer.

Can improve medicine also can be included among the soluble composition the infiltrative suitable penetration enhancer of mucosa.When using non-lipophilic drugs, penetration enhancer may be even more important, and also may be useful for lipophilic drugs.Can include but not limited to bile salt with the example of within the scope of the present invention typical penetration enhancer; sodium cholate for example; NaGC; glycodesoxycholic acid sodium; taurodeoxycholate; NaTDC; lithocholic acid sodium; the Fel Anseris domestica hydrochlorate; chenodesoxy cholate; the Fel Ursi hydrochlorate; ursodeoxycholic acid salt; hydrodeoxygenation cholic acid (hydrodeoxycholate); dehydrocholate; glycochenodeoxycholate salt; taurochenodeoxycholate and cattle sulphur chenodesoxy cholate; and sodium lauryl sulphate (" SDS "); dimethyl sulfoxine (" DMSO "); sodium laurylsulfate; salt and other derivant of saturated and unsaturated fatty acid; surfactant; the bile salt analog, the bile salt derivant.In addition, can also use as U.S. Patent No. 4,746, the synthetic penetration enhancer described in 508, the full content of described patent is included in by the mode of quoting at this.

One skilled in the art will appreciate that if thin film needs of the present invention, also can use the filler and the extender of kind known in the art, include but not limited to lactose or gelatin.

The material that adds above-mentioned dissolvable matrix can be the nitroglycerin of appropriate amount.As discussed in detail below, nitroglycerin or the thin film that comprises any other therapeutic agent are easy in the doped matrix compositions, thereby produce edible of the present invention or digestible thin film that comprises nitroglycerin, or comprise the thin film of other therapeutic agent.

Can mix various required components to produce compositions of the present invention.When mixing various component, it may be useful using the method for how much dilutions (geometric dilution), but not necessarily.Use this method, the composition of two kinds of weight minimums (with the proportional meter of final products) is at first fully mixed.

When reaching between two kinds of components when mixing fully, add the weight time less component suitable and fully mix with existing mixture with aforementioned component.Repeat this step, all add mixture and mix fully with all other components until all components.

How much dilutions make all components be able to mix fully and fully.Adopt said method, make that undercompounding and component probability pockety in whole mixture is less.Because product is insoluble, other existing method may cause mixing not exclusively.

In case realize mixing fully, described mixture just can be made the solid solubility base composition.In one embodiment, described mixture can be suppressed under elevated pressures, to produce adherent batching.About 2000 newton extremely about 5000 newton's pressure are suitable, but also can use any pressure that is enough to described component is pressed into adherent monoblock material.

In other embodiment within the scope of the present invention, required composition can be by dehydration, lyophilization (lyophilization), be poured in the mould, be sprayed on the suitable holder, gas deposition, centrifugal or known in the art other technology are made dosage form.

When production comprises the edible film of nitroglycerin or any other therapeutic agent, may not need as the past the preparation pastille confection in employed method with mixture heated to molten mass.Therefore,, can avoid the nitroglycerin in the thin film or the thermal decomposition of any other therapeutic agent, and produce the product of homogeneous in the well-mixed while.

Except nitroglycerin, it will be apparent to one skilled in the art that other forms of pharmacologically active agents also can add the present invention and comprise in the edible film of nitroglycerin.Perhaps, described forms of pharmacologically active agents can not be formulated in the edible film under having the situation of nitroglycerin.Wording as used herein " forms of pharmacologically active agents " is intended to comprise the reagent except that food, and described reagent promotes structure and/or changing function in using the body of this reagent and/or on the body.Described reagent does not specifically limit; But they should be physiologically acceptable and have the compatibility with described thin film.Suitable forms of pharmacologically active agents includes but not limited to:

A. antimicrobial, for example triclosan, cetylpyridinium chloride(CPC), domiphen bromide, quaternary ammonium salt, zinc compound, Sanguinarine, fluoride, alexidine, octonidine, EDTA or the like,

B. NSAID (non-steroidal anti-inflammatory drug), for example aspirin, acetaminophen, ibuprofen, ketoprofen, Diflonid, fenoprofen calcium, naproxen, tolmetin sodium, indomethacin or the like,

C. cough medicine, for example benzonatate, caramiphen edisylate, menthol, dextromethorphan hydrobromide, Coldrin (Nippon Shinyaku) or the like,

D. separate congested agent, for example pseudoephedrine hydrochloride, phenylephrine, phenylpropanolamine, pseudoephedrine sulfate or the like,

E. antihistaminic, for example brompheniramine maleate, chlorphenamine maleate, carbinoxamine maleate, tavehil, dexbrompheniramine maleate, diphhydramine hydrochloride, diphenylpyraline hydrochloride, azatadine maleate, diphenhydramine citrate, doxylamine succinate, promethazine hydrochloride, Pyrilamine, tripelennamine citrate, triprolidine hydrochloride, acrivastine, loratadine, brompheniramine, dexbrompheniramine or the like

F. expectorant, for example guaifenesin, hippo, potassium iodide, dipentene glycol or the like,

G. diarrhea, loperamide or the like for example,

The H.H2-antagonist, for example famotidine, ranitidine or the like,

I. proton pump inhibitor, for example omeprazole, lansoprazole or the like,

J. the non-selective central nervous system depressant of whole body, for example aliphatic alcohols, barbiturates or the like,

K. the non-selective central nervous system stimulant of whole body, for example caffeine, nicotine, strychnine, Picrotoxin, pentetrazole or the like,

L. the medicine of selectively changing central nervous system function, for example phenyl hydantoin is because of (phenyhydantoin), phenobarbital, primidone, carbamazepine, ethosuximide, mesuximide, phensuximide, trimethadione, diazepam, Benzodiazepines, phenacal, ethylphenacemide, acetazolamide, easypro thiazine, bromide or the like

M. antiparkinsonism drug, for example levodopa, amantadine or the like,

N. narcosis analgesic, alfentanil for example, benzyl morphine; buprenorphine; Clonitazene; codeine; Desomorphine; dextromoramide; dimethylthiambutene; eptazocine; ethoheptazine; fentanyl; hydrocodone; hydromorphone; hydroxypethidine; isomethadone; cetobemidone; levorphanol; lofentanil; Pethidine; methadone hydrochloride; metopon; morphine; nalbuphine; nalorphine; naloxone; naltrexone; norlevorphanol; opium; oxycodone; oxymorphone; papaveretum; phenadoxone; Promedrol; sufentanil; tilidate or the like

O. antipyretic analgesic, for example willow acid ester (salycilate), Phenylbutazone, indomethacin, phenacetin, aryl sulfonamide derivant (arylsulfanyl) and heteroaryl sulfonamides (heterosulfanyl) derivant are (referring to U.S. Patent Application Serial No.2003/0078236, include in by the mode of quoting at this) or the like

P. psychopharmacology medicine, for example chlorpromazine, methotrimeprazine, haloperidol, clozapine, reserpine, imipramine, tranylcypromine, phenelzine, lithium or the like,

Q. resisting hypertension and cardiovascular treatment agent, for example ACE inhibitor, potassium channel antagonists, peripheral vasodilator agent, beta-adrenergic blocking agent, α/beta-adrenergic blocking agent, diuretic, Folium Digitalis Purpureae and comprise Dilatrate-SR and the sorbide nitrate of isosorbide mononitrate

R. Dermatological Agents, Acitretin for example, algestone acetophenide (algesteone acetophenide), ammonium salicylate, anthralin, azathioprine, the 6-azauridine, Azelaic Acid, benzoyl peroxide, bergapten, 5,7-dichloro-8-hydroxyquinoline, Purified Goa powder, cyclophosphamide, ciclosporin, cyctol, cyproterone, dichloroacetic acid, doxycycline, etretinate, isotretinoin, the 3-O-Lauroylpyridoxol Diacetate, methotrexate (Methotrxate), minocycline, motretinide, piroctone, PTO, 1,2,3,-thrihydroxy-benzene, resorcinol, tretinoin, salicylic acid, selenium sulfide, tazarotene, tetroquinone, tioxolone or the like

S. glucocorticoids and steroidal compounds, 21-acetoxypregnenolone for example, alclometasone, algestone, betamethasone, beclometasone, budesonide, clobetasol, corticosterone, cortivazol, deflazacort, dexamethasone, desoximetasone, difluprednate, enoxolone, Fluazacort, Cortexilar, fluocortin butyl, Cordran, fluderma, halcinonide, halopredone acetate, hydrocortisone, mazipredone, methylprednisolone, the methyl paramethasone, prednisolone, Prednisonum (predinisone), W-4869, prednylidene, 21-lignocaine acetate, tixocortol, Triamcinolone or the like

T. anti-malarial agents and antiparasitic, for example acedapsone, bebeerine, chirate, proguanil, chloroquine, ledger bark, gentiopicrin, Halofantrine, oxychloroquine, Mefloquine Hydrochloride, quinacrine, 3-methylarsacetin, praequine, primaquine, pyrimethamine, quiacrine, quinine, quinocide, quinoline and natrium arsenicum or the like

U. antifungal, acrisorcin for example, amorolfine, amphotericin B, azaserine, bifonazole, xenysalate, bromosalicylchloranilide, buclosamide, butoconazole, calcium propionate, cannitracin, clodantoin, chlorphenesin, ciclopirox, cloxiquine, Dermastatin., diamthazole dihydrochloride, econazole, enilconazole, exalamide, fenticonazole, filipin, fluconazol, flucytosine, fungichromin, griseofulvin, hachimycin, haletazole, hexetidine, Itraconazole, isoconazole, itraconazole, ketoconazole, loflucarban, lucimycin, mepartricin, miconazole, naftifine, natamycin, neodecyllin, nifuratel, nystatin, oligomycin, omoconazole, oxiconazole, pecilocin, potassium iodide, Aminomycin, salicylanilide, siccanin, sulconazole, terbinafine, terconazole (triaconazole), tioconazole, tubercidin, tolciclate, ujothion, viridin, zinc propionate or the like

V. periodontitis agent, for example cevimeline hydrochloride, chlorhexidine, doxycycline, fluoride, minocycline, pilocarpine, tetracycline, triclosan or the like,

W. emetic, for example apocodeine, apomorphine, cephaeline, hippo, sodium chloride, zinc acetate or the like,

X. the therapeutic agent of gout, for example allopurinol, Carprofen, colchicine, probenecid, sulfinpyrazone or the like,

Y. glaucomatous therapeutic agent, for example acetazolamide, befunolol, betaxolol, bupranolol (burpranolol), carteolol, dapiprazole, daranide, dipivefrine, epinephrine, levobunolol, methazolamide, metipranolol, pilocarpine, pindolol, timolol or the like

Z. the therapeutic agent of scatterbrained hyperactivity disorder, for example methylphenidate, dextro-amphetamine, pemoline, athomexetine or the like,

AA. to the pretreat and the therapeutic agent of contact chemical weapons (for example never poison), for example atropine, pralidoxime (2-PAM), pralidoxime chloride, diazepam, pyridostigmine or the like,

BB. the therapeutic agent of acute roentgenization, potassium iodide, Prussian blue or the like for example,

CC. hemorrhage, for example Adrenalone, adrenale, algin, alginic acid, aminochrome, batroxobin, carbazochrome salicylate, cephalin, cotarnin, ellagic acid, etamsylate, factor viii, factor ix, factor xiii, 1,2-naphthylamine-4-sulfonic acid, oxamarin, oxidized cellulose, hemostatic colllodion, sulmarin, thrombin, Thromboplastin, tolonium chloride, tranexamic acid, vassopressin, Menaquinone K6 or the like

DD.Sj rgren ' s syndrome or the syndromic therapeutic agent of xerostomia, for example pilocarpine (Salagon) and cevimeline hydrochloride (Evoxac), and;

EE. agent, for example nicotine, bupropion hydrochloride, lobeline, clonidine, nortyptaline or the like give up smoking.

But prepare nitroglycerin or other therapeutic agent in edible of the present invention or the digestible film, make the each several part thin film have given dose.If nitroglycerin is evenly distributed on the whole thin film with known or set concentration, can calculate dosage contained in the thin film with thickness, width and the length of thin film so.Perhaps, when thickness, width and the length of described thin film are all unified, can adjust the nitroglycerin that adds in the thin film composition or the amount of other therapeutic agent, so that required dosage to be provided.

From following specific embodiment, will be clear that other purpose of the present invention, feature and advantage.Although described embodiment has illustrated specific embodiments of the present invention, it only for the purpose of description.Therefore, the present invention also comprises various variations and the change that drops in the spirit and scope of the invention, and those skilled in the art are easy to know described variation and change from concrete narration.

Embodiment

By following examples,, still should be understood that the present invention can not be considered as only limiting to this with the present invention will be described in more detail.

Embodiment 1:

Use following method to prepare the nitroglycerin thin film, and comprise other therapeutic agent and contain or do not contain the thin film of nitroglycerin:

1. except Polysorbate 80 and Atmos 300, film forming component (for example xanthan gum, carob gum, carrageenin and amylopectin) is mixed aquation in the pure water be incorporated in heat, thereby form gel and in about 4 ℃ of refrigerators, store and spend the night to form goods A.

2. in pure water, add coloring agent, copper gluconate and sweeting agent, and make it to be dissolved in the pure water to form goods B.

3. goods B is added among the goods A, and fully mix to form goods C.

4. mix flavoring agent to form goods D.

5. Polysorbate 80 and Atmos 300 are added among the goods D, and fully mix to form goods E.

6. goods E is added among the goods C, and fully mix to form goods F.

Nitroglycerin or other therapeutic agent are added in any said products with required amount, so that finished films has required dosage.Goods F is cast on the mould and cast form at room temperature is the thin film with desired thickness.Described thin film is dry and cut into required size in hot-air, and packing is also stored.

Embodiment 2:

Adopt the preparation of following method to comprise the edible film of nitroglycerin, and comprise other therapeutic agent and contain or do not contain the thin film of nitroglycerin, described method comprises the following steps:

1. copper gluconate, acesulfame K, aspartame, glycerol, sorbitol and dyestuff are dissolved in pure water, to form aqueous mixture;

2. pulverous amylopectin, xanthan gum, carob gum and carrageenin are mixed, to form mixture of powders;

3. the mixture of powders with step B adds in the aqueous mixture of steps A, to form hydrated polymer gel;

4. at room temperature the hydrated polymer of low speed (about 50-100RPM) whipping step C spends the night;

5. the homogeneous mixture with step D is cast on the suitable holder; And

6. dry mixture of being cast is to form thin film.

Nitroglycerin or other therapeutic agent can be added steps A to arbitrary mixture of D, so that finished films has required dosage with required amount.Described finished films is cut into required size and stores.

Therefore can see that the present invention possesses great motility aspect the suitable edible pastille thin film making up.Medication amount contained in any edible film can change in very wide scope.

Embodiment 3:

Comprise the edible film of nitroglycerin, or comprise the thin film of any other therapeutic agent can be by being prepared as follows:

1. in water, add sodium benzoate and sweeting agent.

2. mix carob gum, xanthan gum and carrageenin.

3. also mix in the mixture with glue mixture adding step 1 until dissolving.

4. so that the amount of required dosage in the finished films can be provided, with nitroglycerin or other therapeutic agent and water or mixed with propylene glycol.

5. the composition that all the other are required adds in the mixture of step 4, or mixes all the other required compositions separately.

6. the mixture with step 4 and step 5 adds in the mixture of step 3.Casting is also dry with the generation thin film, and cuts into the size of the required dosage that can satisfy required nitroglycerin dosage or other therapeutic agent.

Embodiment 4:

1. in being heated to 50 ℃ water, add sodium benzoate.Mix and make its dissolving.

2. respectively Peg 1450, titanium dioxide and nitroglycerin or other therapeutic agent are added in the mixture of step 1, all mix after each the adding.The nitroglycerin that is added or the amount of other therapeutic agent should be able to make finished films have required dosage.

3. mix carob gum, xanthan gum and carrageenin.

4. glue is added in the mixture of step 2 and mix until dissolving.

5. all the other compositions are added to together, and heat as required.

6. the mixture with step 4 and step 5 is added to together.Casting is also dry to produce thin film and to cut into the size that can obtain required dosage.

Prepare nitroglycerin or other therapeutic agent in the edible film of the present invention, so that the each several part thin film has given dose.If nitroglycerin or other therapeutic agent are evenly distributed on the whole thin film with known or set concentration, can calculate dosage contained in the thin film with thickness, width and the length of thin film so.Perhaps, when thickness, width and the length of described thin film are all unified, can adjust the nitroglycerin that adds in the thin film composition or the amount of other therapeutic agent, so that required dosage to be provided.

Embodiment 5:

The edible film that comprises nitroglycerin or any other therapeutic agent, can be by being prepared as follows:

1. in deionized water, add the hydrocolloid starch solution, and with high shear mixing until forming clarifying aqueous solution.

2. deionized water is heated to 40 ℃, adds protein solution (for example gelatin) and slowly stir and dissolve until protein; Cool the temperature to 30 ℃.

3. in the mixture of step 1 and step 2, add Sorbo Sorbitol solution and Polysorbate 80, and mix until dissolving.

6. the mixture with step 4 and step 5 adds in the mixture of step 3.Adopt roller scraper dispense tip (knife-over-roll coating head) to be cast to and be coated with on the poly inhomogeneous release paper, dry with the generation thin film in drying tunnel, and cut into the size that can obtain required dosage.

Embodiment 6:

The edible film that comprises nitroglycerin or any other therapeutic agent, can be by being prepared as follows: 1. with maltodextrin, sodium alginate and 10 microcrystalline Cellulose be heated to ebullient water and mix, stir simultaneously.

2. mixture is cooled between 35 ℃ to about 40 ℃, in mixture, adds mixture, sweeting agent, softening agent and the coloring agent of flavoring agent/emulsifying agent.

3. so that the amount of required dosage in the finished films can be provided, with nitroglycerin or other therapeutic agent and water or mixed with propylene glycol.

4. the composition that all the other are required adds in the mixture of step 3, or mixes all the other required compositions separately.

5. the mixture in step 3 and the step 4 is added in the mixture of step 2.

6. utilize scraper (draw down blade) to be coated on the glass plate, make solution in 40 ℃ of baking ovens dry about 15 minutes producing thin film, and cut into the size that can obtain required dosage.

Embodiment 7:

1. the beta glucan that mixes purification in hot water is to form beta glucan solution.

2. so that the amount of required dosage in the finished films can be provided, with nitroglycerin or other therapeutic agent and water or mixed with propylene glycol.

3. the composition that all the other are required adds in the mixture of step 2, or mixes all the other required compositions separately.

4. liquid mixture is poured into 150 ℃ last 15 minute of thermal capacitance device (bomb), so that moisture evaporates from solution.

5. thin film is torn from hot surface, further dry in 70 ℃ of baking ovens, and cut into the size of the required dosage that can obtain nitroglycerin or other therapeutic agent.

Claims

1. but orally-dissolvable digestible film that is suitable for the patient, wherein said thin film comprises nitroglycerin and water-soluble polymer.

But 2. the digestible film of claim 1, wherein said water-soluble polymer is selected from amylopectin, hydrocolloid, beta glucan, maltodextrin, comprise hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methylcellulose, hydroxy methocel, hydroxyethyl-cellulose is at interior cellulose, polyvinylpyrrolidone, polyvinyl alcohol, sodium alginate, Polyethylene Glycol, such as carob gum, carrageenin, xanthan gum, Tragacanth, guar gum, acacia gum, arabic gum, karaya, the natural gum that rolls, the natural gum of tamarind gum, polyacrylic acid, the methylmethacrylate copolymer, carboxy vinyl polymer, amylose, high amylose starches, the hydroxypropylation high amylose starches, dextrin, pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, zein, baregin, soy protein isolate, lactalbumin isolate, casein and composition thereof.

3. but the digestible film of claim 2, wherein said water-soluble polymer is an amylopectin.

4. but the digestible film of claim 3 comprises about amylopectin of 40 to about 80wt%; About thymol of 0.01 to about 4wt%; About methyl salicylate of 0.01 to about 4wt%; About cineole of 0.01 to about 4wt%; With about menthol of 0.01 to about 15wt%.

5. but the digestible film of claim 2 further comprises about 0.01 to about 5wt% at least a stabilizing agent; About 0.001 to about 0.1wt% at least a coloring agent; About water of 0.1 to about 8wt%; About 0.1 to about 15wt% at least a sweeting agent; About 0.1 to about 15wt% at least a flavoring agent; About 0.1 to about 4wt% at least a coolant; About 0.1 to about 5wt% at least a surfactant.

6. but the digestible film of claim 5, wherein said at least a stabilizing agent is selected from xanthan gum, carob gum and carrageenin, and described at least a sweeting agent is selected from glucide, aspartame and acesulfame-K.

7. but the digestible film of claim 1, wherein said thin film self does not adhere to basically.

8. but the digestible film of claim 1 further comprises about water of 3 to about 8wt%.

9. method for preparing the edible film that comprises nitroglycerin, described method comprises: at least a water-soluble film forming agent is mixed to produce the film forming mixture; In the film forming mixture, add nitroglycerin; The film forming mixture that will comprise nitroglycerin is cast on the substrate; And dry casting film is to produce the described edible film that comprises nitroglycerin.

10. the method for claim 9 wherein is mixed at least a surfactant in the described film forming mixture.

11. it is till about 3 to about 8wt% that the method for claim 9, wherein said drying proceed to the water content of described thin film.

12. the method for claim 9, wherein said film forming mixture is a powder, and this powder can directly combine with the aqueous solution that comprises nitroglycerin to form hydrated polymer gel.

13. the method for claim 12, the formation of wherein said hydrated polymer gel need not heated.

14. the method for claim 13, wherein said hydrated polymer gel at room temperature stirred about 2 hours to about 48 hours.

15. self adhering film of producing according to the method for claim 9 not that comprises nitroglycerin.

16. the method for claim 9, wherein said water-soluble film forming agent is selected from amylopectin, hydrocolloid, beta glucan, maltodextrin, comprise hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methylcellulose, hydroxy methocel, hydroxyethyl-cellulose is at interior cellulose, polyvinylpyrrolidone, polyvinyl alcohol, sodium alginate, Polyethylene Glycol, such as carob gum, carrageenin, xanthan gum, Tragacanth, guar gum, acacia gum, arabic gum, karaya, the natural gum that rolls, the natural gum of tamarind gum, polyacrylic acid, the methylmethacrylate copolymer, carboxy vinyl polymer, amylose, high amylose starches, the hydroxypropylation high amylose starches, dextrin, pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, zein, baregin, soy protein isolate, lactalbumin isolate, casein and composition thereof.

17. the method for claim 16, wherein said water-soluble film forming agent is an amylopectin.

18. but an orally-dissolvable digestible film that comprises nitroglycerin that is suitable for the patient, wherein said thin film includes nitroglycerin in containing a monolayer of amylopectin and at least a other medicinal reagent.

But 19. the digestible film of claim 18, wherein said medicinal reagent is selected from antimicrobial, NSAID (non-steroidal anti-inflammatory drug), cough medicine, decongestant, antihistaminic, expectorant, diarrhea, H ₂-antagonist, proton pump inhibitor, the non-selective central nervous system depressant of whole body, the non-selective central nervous system stimulant of whole body, the medicine of selectively changing central nervous system function, antiparkinsonism drug, narcosis analgesic, antipyretic analgesic, the psychopharmacology medicine, resisting hypertension and cardiovascular treatment agent, Dermatological Agents, glucocorticoids and steroidal compounds, anti-malarial agents and antiparasitic, antifungal, the periodontitis agent, emetic, the therapeutic agent of gout, glaucomatous therapeutic agent, the therapeutic agent of scatterbrained hyperactivity disorder, the pretreat and the therapeutic agent of contact chemical weapons, the therapeutic agent of acute roentgenization, hemorrhage, the syndromic therapeutic agent of Sj  rgren ' s, smoking cessation agent and composition thereof.

But 20. the digestible film of claim 19, wherein said antimicrobial is selected from triclosan, cetylpyridinium chloride(CPC), domiphen bromide, quaternary ammonium salt, zinc compound, Sanguinarine, fluoride, alexidine, octonidine, EDTA and composition thereof.

But 21. the digestible film of claim 19, wherein said NSAID (non-steroidal anti-inflammatory drug) is selected from aspirin, acetaminophen, ibuprofen, Diflonid, fenoprofen calcium, naproxen, tolmetin sodium, indomethacin and composition thereof.

But 22. the digestible film of claim 19, wherein said cough medicine is selected from benzonatate, caramiphen edisylate, dextromethorphan hydrobromide, Coldrin (Nippon Shinyaku) and composition thereof.

23. but the digestible film of claim 19 is wherein saidly separated congested agent and is selected from pseudoephedrine hydrochloride, phenylephrine, phenylpropanolamine and composition thereof.

But 24. the digestible film of claim 19, wherein said antihistaminic is selected from brompheniramine maleate, chlorphenamine maleate, carbinoxamine maleate, tavehil, dexbrompheniramine maleate, diphhydramine hydrochloride, diphenhydramine citrate, diphenylpyraline hydrochloride, doxylamine succinate, promethazine hydrochloride, Pyrilamine, tripelennamine citrate, triprolidine hydrochloride and composition thereof.

But 25. the digestible film of claim 19, wherein said expectorant is selected from guaifenesin, hippo, potassium iodide, dipentene glycol and composition thereof.

But 26. the digestible film of claim 19, wherein said diarrhea is a loperamide.

But 27. the digestible film of claim 19, wherein said H2-antagonist is selected from famotidine, ranitidine and composition thereof.

But 28. the digestible film of claim 19, wherein said proton pump inhibitor is selected from omeprazole, lansoprazole and composition thereof.

But 29. the digestible film of claim 19, the non-selective central nervous system depressant of wherein said whole body is selected from aliphatic alcohols, barbiturates and composition thereof.

But 30. the digestible film of claim 19, the non-selective central nervous system stimulant of wherein said whole body is selected from caffeine, nicotine, strychnine, Picrotoxin, pentetrazole and composition thereof.

But 31. the digestible film of claim 19, the medicine of wherein said selectively changing central nervous system function be selected from phenyl hydantoin because of, phenobarbital, primidone, carbamazepine, ethosuximide, mesuximide, phensuximide, trimethadione, diazepam, Benzodiazepines, phenacal, ethylphenacemide, acetazolamide, thiazine, bromide and composition thereof relax.

But 32. the digestible film of claim 19, wherein said antiparkinsonism drug is selected from levodopa, amantadine and composition thereof.

But 33. the digestible film of claim 19, wherein said narcosis analgesic is selected from alfentanil, benzyl morphine; buprenorphine; Clonitazene; codeine; Desomorphine; dextromoramide; dimethylthiambutene; eptazocine; ethoheptazine; fentanyl; hydrocodone; hydromorphone; hydroxypethidine; isomethadone; cetobemidone; levorphanol; lofentanil; Pethidine; methadone hydrochloride; metopon; morphine; nalbuphine; nalorphine; naloxone; naltrexone; norlevorphanol; opium; oxycodone; oxymorphone; papaveretum; phenadoxone; Promedrol; sufentanil; tilidate and composition thereof.

But 34. the digestible film of claim 19, wherein said antipyretic analgesic is selected from willow acid ester, Phenylbutazone, indomethacin, phenacetin, aryl sulfonamide derivant and heteroaryl sulfonamide and composition thereof.

But 35. the digestible film of claim 19, wherein said psychopharmacology medicine is selected from chlorpromazine, methotrimeprazine, haloperidol, clozapine, reserpine, imipramine, tranylcypromine, phenelzine, lithium and composition thereof.

But 36. the digestible film of claim 19, wherein said resisting hypertension and cardiovascular treatment agent are selected from ACE inhibitor, potassium channel antagonists, peripheral vasodilator agent, beta-adrenergic blocking agent, α/beta-adrenergic blocking agent, diuretic, Folium Digitalis Purpureae and comprise Dilatrate-SR and the sorbide nitrate of isosorbide mononitrate and composition thereof.

But 37. the digestible film of claim 19, wherein said Dermatological Agents is selected from Acitretin, algestone acetophenide, ammonium salicylate, anthralin, azathioprine, the 6-azauridine, Azelaic Acid, benzoyl peroxide, bergapten, 5,7-dichloro-8-hydroxyquinoline, Purified Goa powder, cyclophosphamide, ciclosporin, cyctol, cyproterone, dichloroacetic acid, doxycycline, etretinate, isotretinoin, the 3-0-Lauroylpyridoxol Diacetate, methotrexate, minocycline, motretinide, piroctone, PTO, 1,2,3,-thrihydroxy-benzene, resorcinol, tretinoin, salicylic acid, selenium sulfide, tazarotene, tetroquinone, tioxolone and composition thereof.

But 38. the digestible film of claim 19, wherein said glucocorticoids and steroidal compounds are selected from the 21-acetoxypregnenolone, alclometasone, algestone, betamethasone, beclometasone, budesonide, clobetasol, corticosterone, cortivazol, deflazacort, dexamethasone, desoximetasone, difluprednate, enoxolone, Fluazacort, Cortexilar, fluocortin butyl, Cordran, fluderma, halcinonide, halopredone acetate, hydrocortisone, mazipredone, methylprednisolone, the methyl paramethasone, prednisolone, Prednisonum, W-4869, prednylidene, 21-lignocaine acetate, tixocortol, Triamcinolone and composition thereof.

But 39. the digestible film of claim 19, wherein said anti-malarial agents and antiparasitic are selected from acedapsone, bebeerine, chirate, proguanil, chloroquine, ledger bark, gentiopicrin, Halofantrine, oxychloroquine, Mefloquine Hydrochloride, quinacrine, 3-methylarsacetin, praequine, primaquine, pyrimethamine, quiacrine, quinine, quinocide, quinoline and natrium arsenicum and composition thereof.

But 40. the digestible film of claim 19, wherein said antifungal is selected from acrisorcin, amorolfine, amphotericin B, azaserine, bifonazole, xenysalate, bromosalicylchloranilide, buclosamide, butoconazole, calcium propionate, cannitracin, clodantoin, chlorphenesin, ciclopirox, cloxiquine, Dermastatin., diamthazole dihydrochloride, econazole, enilconazole, exalamide, fenticonazole, filipin, fluconazol, flucytosine, fungichromin, griseofulvin, hachimycin, haletazole, hexetidine, Itraconazole, isoconazole, itraconazole, ketoconazole, loflucarban, lucimycin, mepartricin, miconazole, naftifine, natamycin, neodecyllin, nifuratel, nystatin, oligomycin, omoconazole, oxiconazole, pecilocin, potassium iodide, Aminomycin, salicylanilide, siccanin, sulconazole, terbinafine, terconazole (triaconazole), tioconazole, tubercidin, tolciclate, ujothion, viridin, zinc propionate and composition thereof.

But 41. the digestible film of claim 19, wherein said periodontitis agent is selected from cevimeline hydrochloride, chlorhexidine, doxycycline, fluoride, minocycline, pilocarpine, tetracycline, triclosan and composition thereof.

42. but the digestible film of claim 19, wherein said emetic is selected from apocodeine, apomorphine, cephaeline, hippo, sodium chloride, zinc acetate and composition thereof.

43. but the digestible film of claim 19, the therapeutic agent of wherein said gout is selected from allopurinol, Carprofen, colchicine, probenecid, sulfinpyrazone and composition thereof.

44. but the digestible film of claim 19, wherein said glaucomatous therapeutic agent is selected from acetazolamide, befunolol, betaxolol, bupranolol, carteolol, dapiprazole, daranide, dipivefrine, epinephrine, levobunolol, methazolamide, metipranolol, pilocarpine, pindolol, timolol and composition thereof.

45. but the digestible film of claim 19, the therapeutic agent of wherein said scatterbrained hyperactivity disorder is selected from methylphenidate, dextro-amphetamine, pemoline, athomexetine and composition thereof.

46. but the digestible film of claim 19, wherein said pretreat and therapeutic agent to the contact chemical weapons is selected from atropine, pralidoxime (2-PAM), pralidoxime chloride, diazepam, pyridostigmine and composition thereof.

47. but the digestible film of claim 19, the therapeutic agent of wherein said acute roentgenization is selected from potassium iodide, Prussian blue and composition thereof.

But 48. the digestible film of claim 19, wherein said hemorrhage is selected from Adrenalone, adrenale, algin, alginic acid, aminochrome, batroxobin, carbazochrome salicylate, cephalin, cotarnin, ellagic acid, etamsylate, factor viii, factor ix, factor xiii, 1,2-naphthylamine-4-sulfonic acid, oxamarin, oxidized cellulose, hemostatic colllodion, sulmarin, thrombin, Thromboplastin, tolonium chloride, tranexamic acid, vassopressin, Menaquinone K6 and composition thereof.

49. but the digestible film of claim 19, the syndromic therapeutic agent of wherein said Sj  rgren ' s is selected from pilocarpine (Salagon) and cevimeline hydrochloride (Evoxac) and composition thereof.

50. but the digestible film of claim 19, wherein said smoking cessation agent is selected from nicotine, bupropion hydrochloride, lobeline, clonidine and nortyptaline.

51. the nitroglycerin with effective dose is delivered to the method in oral cavity, described method comprises puts into the oral cavity with the instant edible film that comprises amylopectin and nitroglycerin.

52. the method for claim 51, the amount of amylopectin is about 40 to about 80wt% in the wherein said thin film.

53. the method for claim 51, the amount of nitroglycerin is about 0.0001 to about 90wt% in the wherein said thin film.

54. the nitroglycerin with effective dose is delivered to the method in oral cavity, but described method comprises the digestible film according to claim 1 is put into the oral cavity.

55. an edible film that comprises nitroglycerin that is used for to patient's transmucosal delivery nitroglycerin, described thin film comprises:

A) soluble binding agent in patient's mouth; With

B) be dispersed in the nitroglycerin of the drug effect dosage in the binding agent, forming the mixture that constitutes thin film, thereby, discharge the nitroglycerin of drug effect dosage when described thin film during patient orally-dissolvable.

But 56. one kind be suitable for orally-dissolvable digestible film the patient, wherein said thin film comprises that one or more are selected from following therapeutic agent: antimicrobial, NSAID (non-steroidal anti-inflammatory drug), anti-inflammatory agent, cough medicine, decongestant, antihistaminic, expectorant, diarrhea, H ₂-antagonist, proton pump inhibitor, the non-selective central nervous system depressant of whole body, the non-selective central nervous system stimulant of whole body, the medicine of selectively changing central nervous system function, antiparkinsonism drug, narcosis analgesic, antipyretic analgesic, the psychopharmacology medicine, resisting hypertension and cardiovascular treatment agent, Dermatological Agents, glucocorticoids and steroidal compounds, anti-malarial agents and antiparasitic, antifungal, the periodontitis agent, emetic, the therapeutic agent of gout, glaucomatous therapeutic agent, the therapeutic agent of scatterbrained hyperactivity disorder, the pretreat and the therapeutic agent of contact chemical weapons, the therapeutic agent of acute roentgenization, hemorrhage, the syndromic therapeutic agent of Sj  rgren ' s, smoking cessation agent and water-soluble polymer.

57. but the digestible film of claim 56, wherein said water-soluble polymer is selected from: amylopectin, hydrocolloid, beta glucan, maltodextrin, comprise hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methylcellulose, hydroxy methocel, hydroxyethyl-cellulose is at interior cellulose, polyvinylpyrrolidone, polyvinyl alcohol, sodium alginate, Polyethylene Glycol, such as carob gum, carrageenin, xanthan gum, Tragacanth, guar gum, acacia gum, arabic gum, karaya, the natural gum that rolls, the natural gum of tamarind gum, polyacrylic acid, the methylmethacrylate copolymer, carboxy vinyl polymer, amylose, high amylose starches, the hydroxypropylation high amylose starches, dextrin, pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, zein, baregin, soy protein isolate, lactalbumin isolate, casein and composition thereof.

58. but the digestible film of claim 57, wherein said water-soluble polymer is an amylopectin.

59. but the digestible film of claim 57 comprises approximately: 40 to about 80wt% amylopectin; About thymol of 0.01 to about 4wt%; About methyl salicylate of 0.01 to about 4wt%; About cineole of 0.01 to about 4wt%; With about menthol of 0.01 to about 15wt%.

60. but the digestible film of claim 57 further comprises: about 0.01 to about 5wt% at least a stabilizing agent; About 0.001 to about 0.1wt% at least a coloring agent; About water of 0.1 to about 8wt%; About 0.1 to about 15wt% at least a sweeting agent; About 0.1 to about 15wt% at least a flavoring agent; About 0.1 to about 4wt% at least a coolant; About 0.1 to about 5wt% at least a surfactant.

61. but the digestible film of claim 60, wherein said at least a stabilizing agent is selected from xanthan gum, carob gum and carrageenin, and described at least a sweeting agent is selected from glucide, aspartame and acesulfame-K.

62. but the digestible film of claim 56, wherein said thin film self does not adhere to basically.

63. but the digestible film of claim 56 further comprises about water of 3 to about 8wt%.

64. a method for preparing edible film, described thin film comprise that one or more are selected from following therapeutic agent: antimicrobial, NSAID (non-steroidal anti-inflammatory drug), anti-inflammatory agent, cough medicine, decongestant, antihistaminic, expectorant, diarrhea, H ₂-antagonist, proton pump inhibitor, the non-selective central nervous system depressant of whole body, the non-selective central nervous system stimulant of whole body, the medicine of selectively changing central nervous system function, antiparkinsonism drug, narcosis analgesic, antipyretic analgesic, the psychopharmacology medicine, resisting hypertension and cardiovascular treatment agent, Dermatological Agents, glucocorticoids and steroidal compounds, anti-malarial agents and antiparasitic, antifungal, the periodontitis agent, emetic, the therapeutic agent of gout, glaucomatous therapeutic agent, the therapeutic agent of scatterbrained hyperactivity disorder, the pretreat and the therapeutic agent of contact chemical weapons, the therapeutic agent of acute roentgenization, hemorrhage, syndromic therapeutic agent of Sj  rgren ' s and smoking cessation agent, described method comprises: at least a water-soluble film forming agent is mixed to produce the film forming mixture; In the film forming mixture, add one or more therapeutic agents; The film forming mixture that will comprise therapeutic agent is cast on the substrate; And dry casting film is to produce the described edible film that comprises therapeutic agent.

65. the method for claim 64 wherein is mixed at least a surfactant in the described film forming mixture.

66. it is till about 3 to about 8wt% that the method for claim 64, wherein said drying proceed to the water content of described thin film.

67. the method for claim 64, wherein said film forming mixture is a powder, this powder can directly combine with the aqueous solution that comprises one or more therapeutic agents, to form hydrated polymer gel, described therapeutic agent is selected from: antimicrobial, NSAID (non-steroidal anti-inflammatory drug), anti-inflammatory agent, cough medicine, decongestant, antihistaminic, expectorant, diarrhea, H ₂-antagonist, proton pump inhibitor, the non-selective central nervous system depressant of whole body, the non-selective central nervous system stimulant of whole body, the medicine of selectively changing central nervous system function, antiparkinsonism drug, narcosis analgesic, antipyretic analgesic, the psychopharmacology medicine, resisting hypertension and cardiovascular treatment agent, Dermatological Agents, glucocorticoids and steroidal compounds, anti-malarial agents and antiparasitic, antifungal, the periodontitis agent, emetic, the therapeutic agent of gout, glaucomatous therapeutic agent, the therapeutic agent of scatterbrained hyperactivity disorder, the pretreat and the therapeutic agent of contact chemical weapons, the therapeutic agent of acute roentgenization, hemorrhage, syndromic therapeutic agent of Sj  rgren ' s and smoking cessation agent.

68. the method for claim 67, the formation of wherein said hydrated polymer gel need not heated.

69. the method for claim 68, wherein said hydrated polymer gel at room temperature stir about 2 to about 48 hours.

70. self adhering film not of producing according to the method for claim 64, described thin film comprises that one or more are selected from following therapeutic agent: antimicrobial, NSAID (non-steroidal anti-inflammatory drug), anti-inflammatory agent, cough medicine, decongestant, antihistaminic, expectorant, diarrhea, H ₂-antagonist, proton pump inhibitor, the non-selective central nervous system depressant of whole body, the non-selective central nervous system stimulant of whole body, the medicine of selectively changing central nervous system function, antiparkinsonism drug, narcosis analgesic, antipyretic analgesic, the psychopharmacology medicine, resisting hypertension and cardiovascular treatment agent, Dermatological Agents, glucocorticoids and steroidal compounds, anti-malarial agents and antiparasitic, antifungal, the periodontitis agent, emetic, the therapeutic agent of gout, glaucomatous therapeutic agent, the therapeutic agent of scatterbrained hyperactivity disorder, the pretreat and the therapeutic agent of contact chemical weapons, the therapeutic agent of acute roentgenization, hemorrhage, syndromic therapeutic agent of Sj  rgren ' s and smoking cessation agent.

71. the method for claim 64, wherein said water-soluble film forming agent is selected from: amylopectin, hydrocolloid, beta glucan, maltodextrin, comprise hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methylcellulose, hydroxy methocel, hydroxyethyl-cellulose is at interior cellulose, polyvinylpyrrolidone, polyvinyl alcohol, sodium alginate, Polyethylene Glycol, such as carob gum, carrageenin, xanthan gum, Tragacanth, guar gum, acacia gum, arabic gum, karaya, the natural gum that rolls, the natural gum of tamarind gum, polyacrylic acid, the methylmethacrylate copolymer, carboxy vinyl polymer, amylose, high amylose starches, the hydroxypropylation high amylose starches, dextrin, pectin, chitin, chitosan, levan, elsinan, collagen, gelatin, zein, baregin, soy protein isolate, lactalbumin isolate, casein and composition thereof.

72. the method for claim 71, wherein said water-soluble film forming agent is an amylopectin.

But 73. one kind be suitable for orally-dissolvable digestible film the patient, wherein said thin film includes one or more therapeutic agents in containing a monolayer of amylopectin, described therapeutic agent is selected from: antimicrobial, NSAID (non-steroidal anti-inflammatory drug), anti-inflammatory agent, cough medicine, decongestant, antihistaminic, expectorant, diarrhea, H ₂-antagonist, proton pump inhibitor, the non-selective central nervous system depressant of whole body, the non-selective central nervous system stimulant of whole body, the medicine of selectively changing central nervous system function, antiparkinsonism drug, narcosis analgesic, antipyretic analgesic, the psychopharmacology medicine, resisting hypertension and cardiovascular treatment agent, Dermatological Agents, glucocorticoids and steroidal compounds, anti-malarial agents and antiparasitic, antifungal, the periodontitis agent, emetic, the therapeutic agent of gout, glaucomatous therapeutic agent, the therapeutic agent of scatterbrained hyperactivity disorder, the pretreat and the therapeutic agent of contact chemical weapons, the therapeutic agent of acute roentgenization, hemorrhage, syndromic therapeutic agent of Sj  rgren ' s and smoking cessation agent.

74. but the digestible film of claim 73, wherein said antimicrobial is selected from triclosan, cetylpyridinium chloride(CPC), domiphen bromide, quaternary ammonium salt, zinc compound, Sanguinarine, fluoride, alexidine, octonidine, EDTA and composition thereof.

75. but the digestible film of claim 73, wherein said NSAID (non-steroidal anti-inflammatory drug) is selected from aspirin, acetaminophen, ibuprofen, Diflonid, fenoprofen calcium, naproxen, tolmetin sodium, indomethacin and composition thereof.

76. but the digestible film of claim 73, wherein said cough medicine is selected from benzonatate, caramiphen edisylate, dextromethorphan hydrobromide, Coldrin (Nippon Shinyaku) and composition thereof.

77. but the digestible film of claim 73 is wherein saidly separated congested agent and is selected from pseudoephedrine hydrochloride, phenylephrine, phenylpropanolamine and composition thereof.

78. but the digestible film of claim 73, wherein said antihistaminic is selected from brompheniramine maleate, chlorphenamine maleate, carbinoxamine maleate, tavehil, dexbrompheniramine maleate, diphhydramine hydrochloride, diphenhydramine citrate, diphenylpyraline hydrochloride, doxylamine succinate, promethazine hydrochloride, Pyrilamine, tripelennamine citrate, triprolidine hydrochloride and composition thereof.

79. but the digestible film of claim 73, wherein said expectorant is selected from guaifenesin, hippo, potassium iodide, dipentene glycol and composition thereof.

80. but the digestible film of claim 73, wherein said diarrhea is a loperamide.

81. but the digestible film of claim 73, wherein said H2-antagonist is selected from famotidine, ranitidine and composition thereof.

82. but the digestible film of claim 73, wherein said proton pump inhibitor is selected from omeprazole, lansoprazole and composition thereof.

83. but the digestible film of claim 73, the non-selective central nervous system depressant of wherein said whole body is selected from aliphatic alcohols, barbiturates and composition thereof.

84. but the digestible film of claim 19, the non-selective central nervous system stimulant of wherein said whole body is selected from caffeine, nicotine, strychnine, Picrotoxin, pentetrazole and composition thereof.

But 85. the digestible film of claim 73, the medicine of wherein said selectively changing central nervous system function be selected from phenyl hydantoin because of, phenobarbital, primidone, carbamazepine, ethosuximide, mesuximide, phensuximide, trimethadione, diazepam, Benzodiazepines, phenacal, ethylphenacemide, acetazolamide, thiazine, bromide and composition thereof relax.

86. but the digestible film of claim 73, wherein said antiparkinsonism drug is selected from levodopa, amantadine and composition thereof.

87. but the digestible film of claim 73, wherein said narcosis analgesic is selected from alfentanil, benzyl morphine; buprenorphine; Clonitazene; codeine; Desomorphine; dextromoramide; dimethylthiambutene; eptazocine; ethoheptazine; fentanyl; hydrocodone; hydromorphone; hydroxypethidine; isomethadone; cetobemidone; levorphanol; lofentanil; Pethidine; methadone hydrochloride; metopon; morphine; nalbuphine; nalorphine; naloxone; naltrexone; norlevorphanol; opium; oxycodone; oxymorphone; papaveretum; phenadoxone; Promedrol; sufentanil; tilidate and composition thereof.

88. but the digestible film of claim 73, wherein said antipyretic analgesic is selected from willow acid ester, Phenylbutazone, indomethacin, phenacetin, aryl sulfonamide derivant and heteroaryl sulfonamide and composition thereof.

89. but the digestible film of claim 73, wherein said psychopharmacology medicine is selected from chlorpromazine, methotrimeprazine, haloperidol, clozapine, reserpine, imipramine, tranylcypromine, phenelzine, lithium and composition thereof.

90. but the digestible film of claim 73, wherein said resisting hypertension and cardiovascular treatment agent are selected from ACE inhibitor, potassium channel antagonists, peripheral vasodilator agent, beta-adrenergic blocking agent, α/beta-adrenergic blocking agent, diuretic, Folium Digitalis Purpureae and comprise Dilatrate-SR and the sorbide nitrate of isosorbide mononitrate and composition thereof.

91. but the digestible film of claim 73, wherein said Dermatological Agents is selected from Acitretin, algestone acetophenide, ammonium salicylate, anthralin, azathioprine, the 6-azauridine, Azelaic Acid, benzoyl peroxide, bergapten, 5,7-dichloro-8-hydroxyquinoline, Purified Goa powder, cyclophosphamide, ciclosporin, cyctol, cyproterone, dichloroacetic acid, doxycycline, etretinate, isotretinoin, the 3-0-Lauroylpyridoxol Diacetate, methotrexate, minocycline, motretinide, piroctone, PTO, 1,2,3,-thrihydroxy-benzene, resorcinol, tretinoin, salicylic acid, selenium sulfide, tazarotene, tetroquinone, tioxolone and composition thereof.

92. but the digestible film of claim 73, wherein said glucocorticoids and steroidal compounds are selected from the 21-acetoxypregnenolone, alclometasone, algestone, betamethasone, beclometasone, budesonide, clobetasol, corticosterone, cortivazol, deflazacort, dexamethasone, desoximetasone, difluprednate, enoxolone, Fluazacort, Cortexilar, fluocortin butyl, Cordran, fluderma, halcinonide, halopredone acetate, hydrocortisone, mazipredone, methylprednisolone, the methyl paramethasone, prednisolone, Prednisonum, W-4869, prednylidene, 21-lignocaine acetate, tixocortol, Triamcinolone and composition thereof.

93. but the digestible film of claim 73, wherein said anti-malarial agents and antiparasitic are selected from acedapsone, bebeerine, chirate, proguanil, chloroquine, ledger bark, gentiopicrin, Halofantrine, oxychloroquine, Mefloquine Hydrochloride, quinacrine, 3-methylarsacetin, praequine, primaquine, pyrimethamine, quiacrine, quinine, quinocide, quinoline and natrium arsenicum and composition thereof.

94. but the digestible film of claim 73, wherein said antifungal is selected from acrisorcin, amorolfine, amphotericin B, azaserine, bifonazole, xenysalate, bromosalicylchloranilide, buclosamide, butoconazole, calcium propionate, cannitracin, clodantoin, chlorphenesin, ciclopirox, cloxiquine, Dermastatin., diamthazole dihydrochloride, econazole, enilconazole, exalamide, fenticonazole, filipin, fluconazol, flucytosine, fungichromin, griseofulvin, hachimycin, haletazole, hexetidine, Itraconazole, isoconazole, itraconazole, ketoconazole, loflucarban, lucimycin, mepartricin, miconazole, naftifine, natamycin, neodecyllin, nifuratel, nystatin, oligomycin, omoconazole, oxiconazole, pecilocin, potassium iodide, Aminomycin, salicylanilide, siccanin, sulconazole, terbinafine, terconazole (triaconazole), tioconazole, tubercidin, tolciclate, ujothion, viridin, zinc propionate and composition thereof.

95. but the digestible film of claim 73, wherein said periodontitis agent is selected from cevimeline hydrochloride, chlorhexidine, doxycycline, fluoride, minocycline, pilocarpine, tetracycline, triclosan and composition thereof.

96. but the digestible film of claim 73, wherein said emetic is selected from apocodeine, apomorphine, cephaeline, hippo, sodium chloride, zinc acetate and composition thereof.

97. but the digestible film of claim 73, the therapeutic agent of wherein said gout is selected from allopurinol, Carprofen, colchicine, probenecid, sulfinpyrazone and composition thereof.

98. but the digestible film of claim 73, wherein said glaucomatous therapeutic agent is selected from acetazolamide, befunolol, betaxolol, bupranolol, carteolol, dapiprazole, daranide, dipivefrine, epinephrine, levobunolol, methazolamide, metipranolol, pilocarpine, pindolol, timolol and composition thereof.

99. but the digestible film of claim 73, the therapeutic agent of wherein said scatterbrained hyperactivity disorder is selected from methylphenidate, dextro-amphetamine, pemoline, athomexetine and composition thereof.

100. but the digestible film of claim 73, wherein said pretreat and therapeutic agent to the contact chemical weapons is selected from atropine, pralidoxime (2-PAM), pralidoxime chloride, diazepam, pyridostigmine and composition thereof.

101. but the digestible film of claim 73, the therapeutic agent of wherein said acute roentgenization is selected from potassium iodide, Prussian blue and composition thereof.

But 102. the digestible film of claim 73, wherein said hemorrhage is selected from Adrenalone, adrenale, algin, alginic acid, aminochrome, batroxobin, carbazochrome salicylate, cephalin, cotarnin, ellagic acid, etamsylate, factor viii, factor ix, factor xiii, 1,2-naphthylamine-4-sulfonic acid, oxamarin, oxidized cellulose, hemostatic colllodion, sulmarin, thrombin, Thromboplastin, tolonium chloride, tranexamic acid, vassopressin, vitamin K ₂And composition thereof.

103. but the digestible film of claim 73, the syndromic therapeutic agent of wherein said Sj  rgren ' s is selected from pilocarpine (Sa 1agon) and cevimeline hydrochloride (Evoxac) and composition thereof.

104. but the digestible film of claim 73, wherein said smoking cessation agent is selected from nicotine, bupropion hydrochloride, lobeline, clonidine and nortyptaline.