CN105229064A - The minimizing of the stress rupture of film - Google Patents

Abstract

Between the shelf lives, reduce or eliminate method and the package of stress rupture for storage films band simultaneously, comprise the package that uses and there is the internal surface be made up of the polymer materials presenting multiple physical property and described package comprises film through annealing and bag.

Description

The minimizing of the stress rupture of film

The cross reference of related application

This application claims the U.S. Patent application the 13/844th submitted on March 15th, 2013, the rights and interests of No. 775, its content is incorporated to herein by reference.

Technical field

The present invention relates to the method and the package that reduce or eliminate the stress rupture between the shelf lives for storage films band simultaneously.

Background technology

Find in finished product and do not observe that the incident of the stress rupture in polymer-based film band is the problem about some polymer-based film products always in process check in 15 minutes or AQL test.In film product stress rupture generally manufacture and packaging after 2 within thoughtful 4 weeks, start occur.Reach a conclusion based on a large amount of presented data analysis of breaking: described problem may cause by giving band by stress in the fabrication process.

The one source of giving the stress of film during manufacture is in drying process.During drying, wet film product is applied in or is coated on substrate, then carries out drying on the substrate.In some drying processs, particularly comprise those of high solvent content, 70% volume that is up to of wet film solution is removed in drying process.Stress is given the film being attached to substrate by this contraction, and film described in curtain coating on substrate also carries out drying to it.Another source of stress relates to cutting process.After initial drying and shrinking, usually film product is cut into independent volume or band.When experiencing the zigzag path cutting operation, described film stands a certain amount of bending operation.

Finally, manufacture and during packing independent film band, this process by around the multiple rotary of roller, by film from strippable substrate with by being used for film product to move to give extra stress by the traction wheel of conversion/packaging machine.When band is individually wrapped in the material with high surface energy, described film affixes to described wrapping material and does not allow to move and discharges stress.Therefore, described stress was released by stress rupture in the time afterwards.

Summary of the invention

In one embodiment, the invention provides the method for the stress rupture for reducing or substantially reduce polymkeric substance in film product (such as, comprising the edible film product of active ingredient) by the surface energy of reduction wrapping material.

In one embodiment, the invention provides for the method by the stress rupture reducing or substantially reduce polymkeric substance in film product (such as, comprising the edible film product of active ingredient (as medicine activity component)) of annealing to film before film being stored in bag or package.

In one embodiment, the invention provides the method for the stress rupture for reducing or substantially reduce polymkeric substance in film product (such as, comprising the edible film of active ingredient (as medicine activity component)) by annealing to the bag or package that comprise film.

In one embodiment, the invention provides for the surface energy by reducing wrapping material and the method by the stress rupture that reduces or substantially reduce polymkeric substance in film product (such as, comprising the edible film of active ingredient (as medicine activity component)) both annealing to film before being stored in by film in bag or package.

In one embodiment, the present invention is by reducing the surface energy of wrapping material and the stress rupture by reducing or substantially reduce polymkeric substance in film product (such as, comprising the edible film of active ingredient (as medicine activity component)) both annealing to the bag of storage films product or package.

In one embodiment, providing a kind of for storing the package comprising the film product of active ingredient (as medicine activity component), comprising: (a) has the top layer of internal surface and outside surface; (b) have the bottom of internal surface and outside surface, top layer and/or bottom comprise polymer materials, and the internal surface of top layer and/or the internal surface of bottom have the adhesive power to film product (such as film) of reduction; Wherein, the internal surface of top layer is partly sealed in the internal surface of bottom, wherein between top layer and bottom, form bag, and wherein film product (such as film) is stored in bag.Do not wish that the internal surface of top layer and/or the internal surface of bottom have the adhesive power to film band of minimizing, because have (i) about 100 degree or larger surface energy by water contact angle thermometrically by any theory constraint; And/or (ii) is as the surface adhesion level being less than about 0.25lbf measured by peel test force, described peel test force uses with the speed drawing of 2 inch per minute clocks and on average through the strap of 1 inch wide and the load block of the distance of 0.75 inch to 1.75 inches; And/or (iii) is as the surface RMS roughness by being less than 800nm under the square level of the sample size of 100 square microns by atomic force microscope measurement.

In one embodiment, provide a kind of package of the film product for storage bag drug containing active ingredient, described package comprises: (a) has the top layer of internal surface and outside surface; (b) there is the bottom of internal surface and outside surface, the internal surface of bottom comprises at least one polymer materials, described polymer materials have be selected from following at least one physical property: (i) is as about 100 degree or larger surface energy by water contact angle thermometrically; (ii) the surface adhesion level being less than about 0.25lbf as measured by peel test force, described peel test force uses with the speed drawing of 2 inch per minute clocks and on average through the strap of 1 inch wide and the load block of the distance of 0.75 inch to 1.75 inches; (iii) as the surface RMS roughness rootmean-square (RMS) by being less than 800nm under the level of the sample size of 100 square microns by atomic force microscope measurement; Wherein, the internal surface of top layer is partly sealed in the internal surface of bottom, between top layer and bottom, form bag.

In one embodiment, provide a kind of for reducing or prevent the method for the stress rupture in film product, described method comprises: the package providing a kind of film product for storage bag drug containing active ingredient, and described package comprises: (a) has the top layer of internal surface and outside surface; (b) there is the bottom of internal surface and outside surface, the internal surface of top layer is sealed at least in part the internal surface of bottom to form bag between the internal surface and the internal surface of bottom of top layer, wherein the internal surface of bottom comprise have be selected from following at least one polymer materials of at least one physical property: (i) is by about 100 degree or larger surface energy of water contact angle thermometrically; And/or (ii) is as the surface adhesion level being less than about 0.25lbf measured by peel test force, described peel test force uses with the speed drawing of 2 inch per minute clocks and on average through the strap of 1 inch wide and the load block of the distance of 0.75 inch to 1.75 inches; And/or (iii) is as the surface RMS roughness by being less than 800nm under the level of the sample size of 100 square microns by atomic force microscope measurement.

In one embodiment, providing a kind of method for reducing the stress rupture in the film comprising continuous and uniform product, said method comprising the steps of:

A () preparation comprises the film forming matrix of solvent, active ingredient and polymer materials;

B () is by casting film-forming matrix and carry out drying to film forming matrix and form dry film;

C () anneals to dry film the stress being released through drying process applying.

In one embodiment, providing a kind of method for reducing stress rupture in film (such as, comprising continuously and the film of uniform product), said method comprising the steps of:

A () preparation comprises the film forming matrix of solvent, active ingredient and polymer materials;

B () is by casting film-forming matrix and carry out drying to film forming matrix and form dry film;

C dry film is packaged in bag by ();

D () anneals to the film through pack the stress being released through drying process applying.

In one embodiment, provide a kind of film product decreasing stress rupture (such as, stress rupture reduced continuously and uniform film product), wherein form described film product by following steps, described step comprises: curtain coating comprises the film forming matrix of solvent, active ingredient and polymer materials, carries out drying to form dry film to film forming matrix; And the stress being released through drying process applying is annealed to dry film.Compared with situation about not being annealed with film, when film is annealed, film product has the stress rupture of minimizing.

In one embodiment, provide a kind of film product decreasing stress rupture (such as, decrease the continuous of stress rupture and uniform film product), wherein form described film product by following steps, described step comprises: casting film-forming matrix and carry out drying to form dry film to film forming matrix; Dry film is packaged in bag; And the stress being released through drying process applying is annealed to the film through pack.Compared with situation about not being annealed with film, when film is annealed, the film through pack has the stress rupture of minimizing.

In one embodiment, provide a kind of for storing the bag comprising the film product of active ingredient (as medicine activity component), described bag comprises the laminate of at least one the first layer and at least one second layer, and at least one the first layer wherein said has internal surface and outside surface; The wherein said second layer is positioned on described the first layer; Wherein said bag comprises the chamber comprising film (such as edible film), and described film comprises at least one polymkeric substance that is positioned at wherein and comprises at least one active ingredient such as medicine activity component be positioned at wherein, and wherein said bag is laminated.Described bag can be made up of the material of any appropriate comprising suitable polymer materials.Anneal to prevent and/or reduce the stress rupture be included in film to film by heating film.After this, film can be placed and be stored in according in bag of the present invention or package.

In one embodiment, provide a kind of for storing the bag comprising the film product of active ingredient (as medicine activity component), described bag comprises the laminate of at least one the first layer and at least one second layer, and wherein at least one the first layer has internal surface and outside surface; Wherein the second layer is positioned on the first layer; Wherein said bag comprises chamber, and described chamber comprises the film of having annealed, and such as, the edible film of having annealed, it comprises at least one polymkeric substance, and also comprise at least one active ingredient be positioned at wherein, such as medicine activity component, wherein said bag is laminated.Described bag can be made up of the material of any appropriate (comprising suitable polymer materials).

In one embodiment, provide a kind of method for reducing stress rupture in film product, described method comprises: (a) provides the sealing bag of the laminate comprising at least one the first layer and at least one second layer, and wherein at least one the first layer has internal surface and outside surface; Wherein at least one second layer has internal surface and outside surface; Wherein the second layer is positioned on the first layer; And wherein said bag comprises chamber, described chamber comprises edible film, it comprises at least one polymkeric substance and is positioned at active ingredient such as medicine activity component wherein, and (b) anneals to prevent and/or reduce the stress rupture in film to described bag by applying heat to described bag.

Accompanying drawing explanation

Fig. 1 shows and compares the result that paper tinsel film peels off test.

Fig. 2 shows the result of the AFM surface RMS roughness test of multiple film.

Fig. 3 shows the ratio of the stress rupture at place's film of multiple times.

Fig. 4 shows the ratio of the stress rupture of the caudacoria 60 day cycle.

Fig. 5 shows the layer for the formation of package of the present invention or bag.

Fig. 6 is the sectional view of package of the present invention.

Fig. 7 is the 2D double refraction figure in " new " (1 week age) film band (illustrating at the top of Fig. 7) and " old " (3 week age) film band (illustrating in the bottom of Fig. 7) before the anneal.

Fig. 8 is the 2D double refraction figure in " new " (1 week age) film band (illustrating at the top of Fig. 8) and " old " (3 week age) film band (illustrating in the bottom of Fig. 8) after anneal.

Embodiment

As used herein, term " annealing " means to change material to discharge the thermal treatment of internal stress etc.

As used herein, term " stress rupture " means the phenomenon occurred in the polymer, and wherein material passes through more weak Van der Waals force together with stronger covalent bonds.When enough local stresses overcome Van der Waals force, form gap thus produce stress crack.These stress cracks can with only visible under the microscope and depend on that the fine crack of the stress in polymkeric substance starts, and polymeric film can be divided into 2 or more sheets along with the time.If polymeric film is by unconfined placement, then when film is allowed to shrink, stress will discharge.But when film is limited by the adhesive power with surface, film can not shrink and will break subsequently.Stress can also by annealing release, and annealing makes the stress in polymkeric substance can discharge and therefore prevent stress rupture.

As used herein, term " medicine ", " medicament ", " medicine " and " active ingredient " can be used alternatingly, and refer to preventing or processing useful material or composition symptom.Described term can comprise medicine, nutritional formulation, hairdressing agent, biotechnological formulation, biologically effective material etc.

It should be understood that term " film " and " film band " comprise the delivery system of any thickness, comprise film and film band, sheet, disk, the thin slice etc. of arbitrary shape (comprising rectangle, square or other shapes expected).Film can be confirmed as length and the width with expectation in the form of the film rolled up continuously or its size.Film described herein can have thickness and the size of any desired being suitable for desired use.Such as, the size of film of the present invention can be defined as it can be placed in the oral cavity of user.The size of other film can be confirmed as being adapted for application to user's skin, and namely local uses.Such as, some films can have the thickness of about 0.1 mil to the relative thin of about 10 mils, and other films can have a little thick thickness of about 10 mils to about 30 mils.Especially those are intended for use to some films of local use, thickness can be larger, namely be greater than about 30 mils.In addition, term " film " comprises individual layer composition and multilayer composition, such as, on laminate film, film coating etc.By the process to film, the composition of dry film form keeps being uniformly distributed of component.Film can comprise medicine bag between two films or district.Film of the present invention can have the size of any desired of the active ingredient being suitable for providing aspiration level, in some embodiments, film has the width of about 10mm to the length of about 50mm and about 10mm extremely about 50mm, can have the shape of any desired, comprise square and rectangle.

As used herein term " dressing " is intended to comprise multilayer film product, and wherein compared with the second layer (or " active ingredient " layer), the first layer (or " back sheet ") is for having the film product of slower rate of decomposition.Dressing described herein usually comprises and being attached to each other or laminated the first layer and the second layer, and wherein compared with the first layer, the second layer has less length and/or width, makes can see the surface of the first layer at least partially in the outside of the second layer.

Film band can be formed by the processing mode of any desired (comprising curtain coating and drying means and extrusion method).Film band can be unitary film or multilayer film.Some examples of the method for formation and desciccator diaphragm are found in United States Patent (USP) the 7th, 425, No. 292, the 7th, 666, No. 337 and the 7th, 357, No. 891, and the content of each in described patent by reference entirety is incorporated to.The active ingredient of any amount or pharmaceutical preparation can be contained in film discussed in this article.Active ingredient can be arranged in the random layer of the film product formed herein or they can be placed on film product one or more on the surface.

At least one region (such as, mucosal areas or the region in the body of user (such as, on the surface of internal)) that the film formed by the present invention can be suitable for the health user is used.In some embodiments of the present invention, film is intended to for Orally administered.In further embodiment, film is intended to for topical application.As used herein, term " topical agent " means to comprise the active ingredient medicament being applied to specific surf zone.Such as, in one embodiment, topical agent is applied to the region of skin.In further embodiment, topical agent can also be applied to the mucosal areas of health, the mouth area (such as, oral cavity, sublingual, tongue) of such as health, vaginal area, eye areas and anal regions.In yet another embodiment, such as, at surgery, topical agent is applied to internal or other body surfaces of user, and wherein after surgical operation completes, medicament is removed or stays in the body.In other embodiments, topical agent is applied to crust, such as, need certain surface areas to be processed.In further embodiment, film of the present invention is absorbable, and to be intended to be placed in the mouth of user and to swallow when described film decomposes.

Medicament can be dispersed in whole film, or its can be arranged on film one or more on the surface.Under often kind of mode, desirably basically identical throughout the amount of whole film per unit area medicament." unit surface " is intended to the area comprising a suitable unit surface such as typical doses unit.It is desirable that, film of the present invention comprises the consistent component distribution of the volume throughout given film.That is, each film product (comprising the individually dosed of roughly equal size) formed by the present invention should have roughly the same content composition each other.Such consistence comprises the basically identical pharmaceutical quantities of the film of per unit volume, no matter medicament still apply in the inside of the matrix of film, laminated or be stabilized in its one or more on the surface.When such film is cut into independent unit, the amount of unit Chinese medicine extremely accurately can be known.For formed film, it will be appreciated by one skilled in the art that final film does not need 100% accurately consistent herein.Required is film " basically identical ", that is, the heterogeneity of small quantity is understood to be acceptable." basically identical " can comprise is such as about 90% consistent film in a region to another region from film at content, or be about 95% consistent film in a region to another region from film at content, and it is more desirable that be about 99% consistent film in a region to another region from film at content.In other words, " basically identical " can mean each film product and relative to each other change and be no more than about 10%.In some embodiments, " basically identical " can mean each film product and relative to each other change and be no more than about 5%.

After the film formation, multiple film bands of similar size (comprising length, width and the degree of depth) can be had from the cutting of film product.Expect that each film band is particularly basically identical each other on active component content on content.When forming film, user is according to the aspiration level target setting active component content of active ingredient in film.Target content refers to 100% of target level.Such as, the film band expected desirably can have the active ingredient of per unit dosage 1mg, and thus 1mg can be " target content ".Should in about 10% of target content from the film band of each basic simlarity size of film product cutting.It is more desirable that, should in about 8% of target content from the film band of each basic simlarity size of film product cutting, or in 6% of target content, or in 4% of target content.For the target content of every dosage unit 1.0mg, basically identical film can have every dosage unit from about 0.90mg to about 1.10mg.When active ingredient is introduced film, by the amount being uniformly distributed the active ingredient determining per unit area of film.Such as, when film is cut into independent formulation, extremely accurately can know the amount of active ingredient in this formulation.Because the amount of active ingredient is in a given area substantially identical with the amount of active ingredient in the region of same size in another part of film, so this is attainable.When active ingredient is medicament (i.e. medicine), the tolerance range of dosage is particularly advantageous.

The active ingredient that can be incorporated in film of the present invention is not limited to medicine and beauty-care activity component, comprise medicine, medicament, protein, antigen or allergen (such as, ragweed pollen), spore, microorganism, seed, Mouthwash Ingredients, essence, spices, enzyme, sanitas, sweeting agent, tinting material, seasonings, VITAMIN and combination thereof.

Various medicaments, biological activity active substance and pharmaceutical composition can be comprised in formulation of the present invention.The example of useful medicine comprises ACE inhibitor, anti-anginal drug, anti-arrhythmic, anti-asthmatic, the sick medicine of anti-cholesterol, analgesic agent, narcotic, anticonvulsive agent, thymoleptic, antidiabetic drug, antidiarrhoea formulation, toxinicide, antihistamine drug, antihypertensive drug, anti-inflammatory agent, lipotropism agent, anti-drying prescription, Antiemetics, anti-stroke agent, anti-thyroid preparation, anticarcinogen, antiviral agent, medicine for acne, alkaloid, amino acid preparation, cough medicine, anti-uricemia medicine, antiviral drug, anabolism preparation, system with nonsystematic anti-infection agent, antitumour drug, anti-Parkinson agent, rheumatism, appetite stimulator, biological response modifier, Hemoregulatory, bone metabolism conditioning agent, cardiovascular agents, central nervous system stimulants, anticholinesterase, contraceptive bian, Decongestant, dietary supplements, dopamine-receptor stimulant, endometriosis management agent, enzyme, remedial agent for erectile dysfunction, cause and educate agent (fertilityagents), stomach and intestine agent, homeopathic drug, hormone, hypercalcemia and low blood calcium management agent, immunomodulator, immunosuppressor, migraine preparations, motion sickness treating agents, muscle relaxant, fat management agent, osteoporosis preparations, oxytocic, parasympatholytic, parasympathomimetic agent, prostaglandin(PG), psychotherapeutic agent, medicine for respiratory system, tranquilizer, smoking cessation auxiliary agent, sympathicolytic, to tremble preparation, medicine for urological system, vasodilator, cathartic, antacid, ion exchange resin, antipyretic, appetite-inhibiting agent, expectorant, antianxiety agent, anti ulcer agent, anti-inflammatory substance, coronary artery diastole agent, cerebral vasodilator, peripheral vasodilators, psychoactive drug (psycho-tropics), stimulant, antihypertensive drug, vasoconstrictor, therapeutic agent for migraine, microbiotic, tranquillizer, antipsychotic drug, anticarcinogen, anti-coagulant, antithrombotic, soporific, antiemetic, Antiemetics, anticonvulsive drug, neuromuscular drug, hyperglycemia agent and hypoglycemia agent, thyroid and antithyroid drug, diuretic(s), spasmolytic, uterine relaxant (terinerelaxant), antiadipositas drug, promoting erythrocyte generates medicine, anti-asthmatic, cough suppressant, apophlegmatisant, DNA and gene alteration medicine and combination thereof.

The example for medicinal activity component of the present invention conceived comprises antacid, H ₂-antagonist and anodyne.Such as, can alone ingredients calcium carbonate or be combined with magnesium hydroxide and/or aluminium hydroxide and prepare antacid.In addition, antacid can with H ₂-antagonist-combination uses.

Anodyne comprises opium and opiate derivative, and such as oxycodone (can be used as obtain), Ibuprofen BP/EP, acetylsalicylic acid, paracetamol and combination thereof, optionally can comprise caffeine.

Other preferred agents of the preferred active ingredient of used other comprise in the present invention: anti-diarrhea agents is R-18553 (immodiumAD), antihistamine drug, cough medicine, decongestant, VITAMIN and breath freshener such as.Can comprise in film composition of the present invention be used singly or in combination for catching a cold, pain, heating, cough, hyperemia, runny nose and allergy common drug, such as paracetamol, chlorpheniramine maleate, Dextromethorphane Hbr, pseudoephedrine hydrochloride and diphenhydramine.

In addition conceived for herein be anxiolytic, such as alprazolam is (passable obtain); Antipsychotic drug such as leoponex (can be used as obtain) and haloperidol (can be used as obtain); Nonsteroid anti-inflammatory drugs (NSAID's) such as diclofenac (can be used as obtain) and R-ETODOLAC (can be used as obtain); Antihistaminic such as Loratadine (can be used as obtain), astemizole (can be used as obtain), nabumetone (can be used as obtain) and clemastine (can be used as obtain); Antiemetic such as Granisetron Hydrochloride (can be used as obtain) and nabilone (can be used as obtain); Bronchodilator such as , salbutamol sulfate (can be used as obtain); Thymoleptic such as fluoxetine Hydrochloride (can be used as obtain), sertraline hydrochloride (can be used as obtain) and paroxetine hydrochloride (can be used as obtain); Antimigraine such as ; ACE-inhibitor such as enalaprilat (can be used as obtain), captopril (can be used as obtain) and lisinopril (can be used as obtain); Kang Aercihaimoshi agent such as nicergoline; And CAH-antagonist such as nifedipine (can be used as with obtain) and verapamil hydrochloride (can be used as obtain).

Remedial agent for erectile dysfunction includes but not limited to for promoting that blood is to penis flowing and the medicine for affecting autonomic nervous activity (such as, strengthening parasympathetic nerve (cholinergic) and reduce sympathetic nerve (suprarenal gland energy) active).(such as, useful non-limiting cartridge bag draws together Virga ), Tadalafei (such as, ), cut down Ta Nafei, Apomorphine (such as, ), Yomax (such as, ) and Prostaglandin E1 (such as, ).

The popular H for using in the present invention conceived ₂-antagonist comprises Cimitidine Type A/AB, ranitidine hydrochloride, famotidine, nizatidine, ebrotidine, mifentidine, roxatidine, huskyly must replace fourth and roxatidine.

Active antacid ingredients includes but not limited to following composition: aluminium hydroxide, Dihydroxyaluminum Aminoacetate, Padil, aluminum phosphate, two oxyaluminum sodium carbonate, supercarbonate, Bismuth Aluminate, Bismuth carbonate, Bismuth Subcarbonate, Bismuth Subgallate, Vikaline, bismuth subsalicylate, calcium carbonate, calcium phosphate, citrate ion (acid or salt), Padil, hydrated sulfuric acid magnalium, magaldrate, neusilin, magnesiumcarbonate, magnesium glycinate, magnesium hydroxide, magnesium oxide, Magnesium Trisilicate, milk solid substance, monocalcium phosphate aluminium or secondary calcium phosphate aluminium, tricalcium phosphate, saleratus, sodium tartrate, sodium bicarbonate, neusilin, tartrate and salt.Medicine activity component used in the present invention can include but not limited to allergen or antigen, such as, from grass, tree or the plant pollen of artemisiifolia; Animal scurf, it is the ramentum come off from the skin and hair of cat and other furbearers; Insect, such as house dust mite, honeybee and wasp; And medicine, such as penicillin.

Antioxidant can also be added to prevent the degraded of active ingredient, particularly when active ingredient is photochromics in film.

Cosmetic activity agent can comprise breath freshening compound (such as menthol), other essence or spices, particularly those compounds for oral hygiene and the active ingredient (as quaternary ammonium hydroxide) for tooth and oral cavity cleaning.Flavour enhancer can be utilized as tartrate, citric acid, Vanillin or analogue to strengthen the effect of taste.

Color additives can also be used in the process preparing film.The additive of such color comprises food pigment, medicine and beauty treatment pigment (FD & C), medicine and beauty treatment pigment (D & C), or externally applied medicine and beauty treatment pigment (external application D & C).The color lake of their correspondence of these pigments is dyestuff and some natural and derivative tinting material.Color lake is the dyestuff adsorbed on aluminum hydroxide.Other examples of tinting material comprise the tinting material of known azoic dyestuff, organic or inorganic pigment or natural origin.Mineral dye is preferred, such as oxide compound or iron or titanium, the concentration of these oxide compounds added account for all components weight about 0.001% to about 10% scope in, and preferably in the scope of about 0.5% to about 3%.Can from natural with the seasoned liquid of synthesis select spices.The illustrative list of such reagent comprises volatile oil, synthesis flavor oil, flavoring aromatics, oil, liquid, oleo-resinous or the extract from plant (leaf, flower, fruit, stem and combination thereof).The non-limiting representational list of example comprises spearmint oil; Cocoa; Oranges and tangerines (such as, lemon, orange, grape, bitter orange and shaddock) oil; And comprise apple, pears, peach, grape, strawberry, raspberry, cherry, plum, pineapple, the fruit essence of apricot or other flavoring agent of fruit.

Can add film containing seasonings with heat is provided or cold flavor beverage or soup.These seasoningss include but not limited to that tea and soup seasonings are as beef and chicken.

Other useful seasoningss comprise aldehydes and ester class, such as phenyl aldehyde (cherry, almond); Citral, i.e. α-citral (lemon, bitter orange); Neral, i.e. neral (lemon, bitter orange); Capraldehyde (orange, lemon); C-8 aldehyde (citrus fruit); C-9 aldehyde (citrus fruit); C-12 aldehyde (citrus fruit); Tolyl aldehyde (cherry, almond); 2,6-dimethyl octanol (green fruit) and 2-dodecylene aldehyde (oranges and tangerines, orange) and combination etc. thereof.

Film product of the present invention can hold the activeconstituents measured on a large scale.Described film can provide accurate dosage (being determined by the concentration of the size of film and the active ingredient in original polymkeric substance/water combines), and is high or very low irrelevant with required dosage.Therefore, according to the type of the active ingredient be incorporated in film or medicine composition, the amount of active ingredient can up to about 300mg, preferably about 150mg or be low to moderate microgram range at the most, or any amount therebetween.

Sweeting agent used in the present invention can be selected from following non-limiting list: glucose (maize treacle), dextrose, Nulomoline, fructose and combination thereof; Asccharin and various salt, such as sodium salt; Dipeptide sweetener, such as aspartame; Dihydrochalcone compound, glycyrrhizin; sweet Stevia(stevioside); The chlorine derivative of sucrose, such as trichlorogalacto-sucrose; Sugar alcohol is Sorbitol Powder, mannitol, Xylitol etc. such as.That it is also conceivable to is hydrogenated starch hydrolysates and synthetic sweetener 3,6-dihydro-6-methyl isophthalic acid-1-1,2,3- thiazine-4-ketone-2,2-dioxide, particularly sylvite (acesulfame potassium) and sodium salt and calcium salt, and natural enhancement sweeting agent, such as Grosvenor Momordica.Other sweeting agents can also be used.

Film product of the present invention and method are suitable for efficient low dosage medicine very much.This is realized by the high consistency of film.Therefore, the more effective racemic mixture of low dosage medicine, particularly active ingredient expects.Described polymkeric substance can be water miscible, water-swellable, water-fast or can be the combination of one or more of water miscible, water-swellable or water-insoluble polymkeric substance.Polymkeric substance can comprise Mierocrystalline cellulose or derivatived cellulose.The specific examples of useful water-soluble polymers includes but not limited to: polyethylene oxide (PEO), amylopectin, Vltra tears (HPMC), Natvosol (HPC), hydroxypropylcellulose, polyvinylpyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodiun alginate, polyoxyethylene glycol, xanthan gum, tragacanth gum, guar gum, kordofan gum, Sudan Gum-arabic, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymer, starch, gelatin and combination thereof.The specific examples of useful insoluble polymer includes but not limited to: ethyl cellulose, Hydroxypropyl ethyl cellulose, cellulosic phthalic acetate, hydroxypropylmethylcellulose phthalate and combination thereof.

As used herein phrase " water-soluble polymers " and variant thereof refer to that it is water-soluble at least partly, and expect complete or water-soluble or absorb the polymkeric substance of water significantly.The polymkeric substance absorbing water is commonly called water-swellable polymer.The material useful to the present invention can be water miscible or water-swellable under room temperature and other temperature (such as, exceeding the temperature of room temperature).In addition, this material can be water miscible or water-swellable under pressure is less than barometric point.It is desirable that, water-soluble polymers is the polymkeric substance of the water-soluble or water-swellable with at least 20 weight percent moisture absorption amounts.The absorbed dose with water is the water-swellable polymer of the weight percent of 25 or larger is also useful.Expect the film that formed by such water-soluble polymers of the present invention or formulation be sufficiently water miscible with solubilized during bioresorbable.

Biodegradable polymkeric substance, multipolymer, block polymer and combination thereof is comprised to being incorporated into other polymkeric substance useful in film of the present invention.Above-mentioned standard is met: poly-(oxyacetic acid) (PGA), poly-(lactic acid) (PLA), polydioxanone, poly-barkite, poly-(α-ester), polyanhydride, poly-acetic ester, polycaprolactone, poly-(ortho ester), polyamino acid, poly-amino-carbon acid esters, urethane, polycarbonate, polymeric amide, poly-(alkyl cyanoacrylate) and composition thereof and multipolymer in known useful polymkeric substance or polymer class.Useful polymkeric substance in addition comprises the space polymer of Pfansteihl and D-ALPHA-Hydroxypropionic acid, the multipolymer of the acid of two (to carboxyphenoxy) propane and sebacic acid, sebacic acid multipolymer, the multipolymer of caprolactone, poly-(lactic acid)/poly-(oxyacetic acid)/ethylene glycol copolymer, the multipolymer of urethane and poly-(lactic acid), the multipolymer of urethane and poly-(lactic acid), the multipolymer of a-amino acid, the multipolymer of a-amino acid and caproic acid, the multipolymer of α-benzyl glutamate and polyoxyethylene glycol, the multipolymer of succinate and poly-(glycol), polyphosphonitrile, PHA and composition thereof.Consider binary and three-part system.

Other concrete useful polymkeric substance comprise with Medisorb and Biodel trade mark sell those.Medisorb material in market sale, and is generally identified as " poly (lactide-co-glycolide) " containing " the 2-hydroxy-polymer of propionic acid and the hydroxy-polymer of oxyacetic acid " by the E.I.Du Pont Company of Wilmington, DE.Four kinds of such polymkeric substance comprise lactide/glycolides 100L, and be considered to the rac-Lactide of 100%, melting range is 338 °F to 347 °F (170 DEG C to 175 DEG C); Lactide/glycolides 100L, is considered to the glycollide of 100%, and melting range is 437 °F to 455 °F (225 ° to 235 DEG C); Lactide/glycolides 85/15, is considered to the glycollide of 85% rac-Lactide and 15%, and melting range is 338 °F-347 °F (170 DEG C to 175 DEG C); With lactide/glycolides 50/50, be considered to the rac-Lactide of 50% and the glycollide of 50%, melting range is 338 °F-347 °F (170 DEG C to 175 DEG C).

Biodel material representative one class has the multiple polyanhydride of different chemical character.

Although multiple different polymkeric substance can be used, expect to select to make mixture have the viscosity of expectation before the drying to polymkeric substance.Such as, if active ingredient or other components insoluble in selected solvent, then expect will provide the polymkeric substance of larger viscosity with help keep consistency.On the other hand, as fruit component is dissolved in this solvent, then the polymkeric substance with less viscosity can preferably be provided.

Polymkeric substance has vital role affecting in film viscosity.Viscosity is a kind of characteristic of liquid, and it controls the stability of active ingredient in emulsion, colloid or suspension.The viscosity of usual matrix is from about 400cps to about 100000cps, preferably from about 800cps to about 60000cps, and is most preferably from about 1000cps to about 40000cps.Desirably the viscosity of film forming matrix can increase sharply after drying process starts.

Viscosity can be regulated based on selected active ingredient according to other compositions in matrix.Such as, as fruit component is insoluble to selected solvent, then suitable viscosity can be selected to prevent components precipitate, precipitate and adverse influence is had to the consistence of the film of gained.Viscosity can be regulated in a variety of ways.In order to increase the viscosity of membrane matrix, can select to have the polymkeric substance of higher molecular weight or adding linking agent, such as calcium salt, sodium salt and sylvite.Viscosity can also be regulated by regulating temperature or adding the component increasing viscosity.The component increasing viscosity or stable emulsion/suspension comprises the polymkeric substance of high molecular and polysaccharide and natural gum, comprising but be not limited to alginate, carrageenin, Vltra tears, Viscogum BE, guar gum, xanthan gum, dextran, Sudan Gum-arabic, gelling gum and combination thereof.

Also observe, usually need softening agent to obtain some polymkeric substance of flexible membrane when used alone, also can combine when there is no softening agent, and also achieve flexible membrane.Such as, when combinationally using HPMC and HPC, be provided for the strong film with suitable plasticity and elastic flexibility manufacturing and store.Do not need to add softening agent or polyvalent alcohol to realize flexibility.

In addition, when being used alone polyethylene oxide (PEO) or being combinationally used with hydrophilic cellulose base polymer by polyethylene oxide (PEO), flexible strong film is achieved.Do not need interpolation softening agent or polyvalent alcohol to realize flexibility.Limiting examples for the suitable cellulose polymer compound combined with PEO comprises HPC and HPMC.PEO and HPC there is no gelling temperature, and HPMC has the gelling temperature (MethocelEF that can obtain from DowChemical company) of 58 DEG C to 64 DEG C.And, even if when substantially also there is enough flexibilities containing these films when organic solvent, can organic solvent be removed and not damage the character of film.Therefore, if do not have solvent, then in film, softening agent is not had.The tear strength that PEO basement membrane has also presented, seldom or do not have curling, and when comprising the PEO of proper level in polymeric constituent, PEO basement membrane also presents fast dissolution rate.

In order to realize the membrane property expected, level and/or the molecular weight of PEO in component of polymer can be changed.Amendment PEO content can influencing characteristic such as tear strength, dissolution rate and adhesive tendencies.Therefore, a kind of method for controlling diaphragm characteristic changes PEO content.Such as, rapidly-soluble film expects in some embodiments.By revising the content of polymeric constituent, desired dissolution characteristics can be realized.

According to the present invention, to be desirably in polymeric constituent PEO in the scope of about 20 % by weight to 100 % by weight.In some embodiments, expect that the amount of PEO is in the scope of about 1mg to about 200mg.Hydrophilic cellulosic polymers in the scope of about 0 % by weight to about 80 % by weight, or is about 4:1 at the most with the ratio of PEO, and expects the ratio for about 1:1.

In some embodiments, expect to change PEO level to promote some film properties.In order to obtain the film with high tear resistance and fast dissolution rate, the level of PEO in polymeric constituent that is desirably in is about 50% or higher.In order to realize preventing adhesion, that is, preventing film to be attached to maxilla, expecting that PEO level is about 20% to 75%.But, in some embodiments, may expect to be attached to maxilla, as animal or children's dispenser.Under these circumstances, the PEO of higher level can be used.More specifically, can the structural integrity of controlling diaphragm and solvability according to the purposes of expection, make film can be attached to mucous membrane and easily be removed, or more firmly and be difficult to removably adhere to.

The molecular weight of PEO can also be changed.Can expect that the PEO of high molecular (such as, about 4,000,000) is to increase the mucoadhesive of film.It is more desirable that the scope of the molecular weight of PEO can be about 100000 to 900000, what more expect is about 100000 to 600000, and what expect most is about 100000 to 300000.In some embodiments, may desirably the PEO of the PEO of high molecular (600000 to 900000) and lower molecular weight (100000 to 300000) be combined in component of polymer.

Such as, can by the PEO of the PEO of a small amount of high molecular and relatively large lower molecular weight be combined to realize some membrane property, such as fast dissolution rate and high tear resistance.It is desirable that, in PEO polymer blend component, such composition comprises about 60% or higher levels of low-molecular-weight PEO.

In order to balance the characteristic preventing adhesion, fast dissolution rate and good tear strength, the film composition expected can comprise the low-molecular-weight PEO of about 50% to 75%, optionally combine with the PEO of a small amount of higher molecular weight, the rest part of polymeric constituent comprises hydrophilic cellulosic polymers (HPC or HPMC).

It is desirable that, film of the present invention comprises polyethylene oxide (PEO), Vltra tears or its combination.

The layer of package of the present invention and bag can comprise the wrapping material of any appropriate.It is desirable that, Low Density Polyethylene (LDPE) and/or ethylene acrylic can be the product contact layers in wrapping material.Once form film band and be cut into suitable desired size, just film band is packed.The packaging of film band contributes to remaining in controlled environment by film band, to keep the integrity of the content of film band and active ingredient.It is desirable that, independent package holds a single film band and sealed, film band is made not to be exposed to outside atmosphere.Usually, film band package is made up of the composition of paper tinsel, polymer materials or paper tinsel and polymer materials.In some embodiments, package is made up of at least one laminated paper tinsel, wherein said paper tinsel and polymer materials laminated.Described package can by user by one or more known methods (comprise such as, tear notch, perforation or by use instrument (such as, scissors or other blades)) open.

Illustrate in Fig. 6 and be suitable for representative package part of the present invention.Illustrate in Fig. 5 and manufactured the top layer 20 comprising outside surface 20A and basal surface 20B and the bottom 30 comprising outside surface 30A and bottom 30A that use in package.As shown in Figure 6, packaging 10 comprises top layer 20 and bottom 30.Top layer 20 comprises the outside surface 20A being exposed to outside atmosphere and the internal surface 20B contacted with the inner bag 40 of package 10.Bottom 30 also comprises the outside surface 30A being exposed to outside atmosphere and the internal surface 30B contacted with the inner bag 40 of package.Film band 50 is included in the inner bag 40 of package 10.Package 10 can be directed along any direction, but for convenience of explanation, Fig. 6 shows the bottom 30 under top surface 20, and film band 50 is positioned on the internal surface 30A of bottom 30.Should be understood that, in some embodiments, film band 50 can contact at least in part with the internal surface 20A of top layer 20.Because film band 50 contacts with internal surface 20A, 30A of package 10 or can contact with internal surface 20A, 30A of package 10, so internal surface 20A, 30A of package 10 should make by relative to film band 50 one or more materials in inertia.The material forming internal surface 20A, 30A of package 10 can not react with film band 50 thus affect film band 50 in the mode of material.

After film band is cut into suitable desired size, place it on the internal surface 30A of package 10, then close and sealed package 10 around film band 50.Film band 50 can retain the time period of prolongation in package 10, and can keep in package more than 10 days, a few week, some months, even several years.In some embodiments, package 10 is suitable for holding film band 50 at least 1 week, or at least 1 month, or at least 6 months, or at least 1 year and harmful damage is not caused to film band 50.In some embodiments, film band 50 retains about 1 month to about 2 years and do not have harmful damage suitably in package 10.In some embodiments, film band 50 retains about 1 month to about 2 years and do not have harmful damage suitably in package 10.

In some embodiments, during the manufacturing stage, on the internal surface of package, directly can form film.In such embodiments, film band is formed with the desired size less than the size of package.

When user wants to use film band, user's open package also takes out film band.Importantly, film band does not adhere to or is attached to the internal surface of package, to make it possible to easily shift out film band.But except easily shifting out film band, the present inventor has been found that the internal surface of package should be made by tolerating the material forming stress rupture in film band.It is especially true when film band is made up of one or more polymer materialss being subject to stress rupture impact.As will be discussed below, the internal surface of package is expected to be made up of one or more materials with low surface energy.In addition, internal surface can have lower surface viscosity relative to the film band be contained in package.In addition, or can in the embodiment of alternative, internal surface can have lower rms surface roughness, as what measure under the sample size scale of 100 square microns.Each characteristic in these characteristics is discussed below.

When using some polymkeric substance in film product, the stress rupture of film is obvious especially.It is in fact highly crystalline or the polymkeric substance that can become highly crystalline that such polymkeric substance comprises those.The significant especially polymkeric substance of the one of stress rupture is caused to be polyethylene oxide (PEO).But polymer materials (such as PEO) is supplied to the many advantages of film product, thus expects to use PEO and analogous material in the process forming film, or be used alone or combinationally use with other polymeric constituents.Such as, PEO can combinationally use with cellulose materials (such as, HPC or HPMC).Unfortunately, have been found that PEO causes many problems owing to often causing stress rupture when user wants to use film.Therefore, some measure should be taked during preparation and packing film band.Such measure uses the wrapping material comprised by the internal surface made by one or more materials of the possibility reducing stress rupture.The material expected comprises those materials had in following characteristics one of at least, and described feature comprises: the internal surface of package is made up of one or more materials with low surface energy; To the film band be accommodated in package, internal surface has low surface viscosity; And internal surface has lower rms surface roughness, as what measure under the sample size scale of 100 square microns.

The present inventor has been noted that to comprise and may stand stress rupture as the unique polymer materials in film or as the film of the PEO of one of polymer materials in film.Even if such film also stands stress rupture on many different wrapping material.Stress rupture is undesirable, because stress rupture has unengaging outward appearance, thus makes the user of film band suspect its completeness and efficiency.The present inventor has been noted that comprising PEO is often attached to various packaging materials as the film of polymeric constituent, thus causes observing more stress rupture when the package is opened.In checking film, a kind of such wrapping material of significant stress rupture are the materials with the internal surface be made up of ethylene acrylic.Nearly 63% stress rupture is demonstrated in the film prepared by such wrapping material.

But, the present inventor has been found that, can form that to comprise be in fact the film of highly crystalline or the polymkeric substance that can become highly crystalline as component of polymer, and there is no stress rupture when being stored in by having lower surface energy, when having on wrapping material that lower surface viscosity or the material with lower surfaceness make.Can by the surface energy of water contact angle thermometrically product.The surface energy expected is about 100 degree or more greatly, measured by being tested by water contact angle.

Load block and strap can be utilized by peel test force surface measurements viscosity.Utilize such test, desired surface has and is less than about 0.25lbf and the Average peel force being less than about 0.20lbf more expected.Finally, can by the RMS roughness of atomic force microscope surface measurements under the sample size level of 100 square microns.Under the sample size level of 100 square microns, the RMS roughness on the surface of the expectation of wrapping material should be less than about 800nm, and is desirably less than about 700nm.

Have and comprise compared with a kind of such wrapping material of low surface energy the material be made up of Low Density Polyethylene (LDPE).When the internal surface of package be made up of the material comprising LDPE time, find stress rupture that is that film band has minimizing or that eliminate.Such internal surface has about 100 degree or larger surface energy as tested by water contact angle, as the surface viscosity by the about 0.25lbf or less measured by peel test force, and by the surface RMS roughness being about 800nm or less measured under the sample size level of 100 square microns of atomic force microscope.

It is desirable that, store at the temperature of about 25 DEG C to about 30 DEG C about after three months, be less than 10% in film band stored in package of the present invention and present stress rupture.

Utilize atomic force microscope (AFM) measure surface roughness.Complete AFM scanning, wherein to each film scan three times (one time 100 μm ², one time 25 μm ²with one time 5 μm ²).Along with the reduction of scan size, the lateral resolution of image increases, and makes little scan size recognize less feature.

Water contact angle test is performed by the pure water droplet utilizing micro pipette to apply 5 microlitres on film.Gather the image of each drop and utilize image procossing to obtain the shape on the surface of each drop, and processing to calculate contact angle to these data.

Utilize the strap being applied to sample film to perform and peel off test.Test 1 inch, sample is wide.By the clip taut band of MTS load block (tester for elongation) that manufactured by MTS Systm Corp. and the end of substrate film.Test is carried out with the speed of 2 feet per minute.Along with sample end is pulled, load rising is until sample is torn and peels off gradually.Start once peel off, according to the local engagement power between strap and substrate film, load is transformable.After medium Opening length, data become more stable, and are averaging test data at the extended distance of 0.75 inch to 1.75 inches.

In some embodiments, additive can optionally be included in film of the present invention, to help improve the internal stress in membrane structure.Such additive can comprise such as, tensio-active agent, softening agent and vitamin-E, TPGS and combination thereof.Such additive can exist with the amount of any appropriate.The appropriate amount of such additive comprises such as about 1 % by weight to about 50 % by weight or higher of film.In some embodiments, softening agent can exist with the amount of about 5 % by weight to about 30 % by weight of film.In some embodiments, softening agent can exist with the amount of about 2 % by weight to about 30 % by weight of film.In some embodiments, softening agent can exist with the amount of about 5 % by weight of film.

By taking some measure at formation packing stage, invention also reduces trend and the possibility of stress rupture.

In some embodiments, can anneal to reduce before being stored in package or bag at film or the basic stress rupture reduced in film to film.In some embodiments, at the temperature of 40 DEG C to 90 DEG C, film is annealed.In some embodiments, with the time of 0.5 minute to 60 minutes, film is annealed.

In some embodiments, by removing film from substrate, annealing to described film and described film is recoiled and anneal to described film at substrate.In some embodiments, at the temperature of 40 DEG C to 90 DEG C, film is annealed.In some embodiments, with the time of 0.5 minute to 60 minutes, film is annealed.In some embodiments, in package, the caudacoria of 3 weeks is complete flawless.

In some embodiments, in package, the caudacoria of 2 months is complete flawless.In some embodiments, in package, the caudacoria of 6 months is complete flawless.In some embodiments, in package, the caudacoria of 12 months is complete flawless.In some embodiments, in package, the caudacoria of 2 years is complete flawless.In some embodiments, in package, the caudacoria of 3 years is complete flawless.In some embodiments, in package, the caudacoria of 3 weeks is complete flawless.In some embodiments, in package, the caudacoria of 2 months is complete flawless.In some embodiments, in package, the caudacoria of 6 months is complete flawless.In some embodiments, in package, the caudacoria of 12 months is complete flawless.In some embodiments, in package, the caudacoria of 2 years is complete flawless.In some embodiments, in package, the caudacoria of 3 years is complete flawless.

In some embodiments, can carry out the package or bag comprising film product (such as, polymeric film) annealing to prevent and/or reduce the stress rupture in film.In some embodiments, in the lehr the package or bag that comprise product are annealed by the sealing bag of product is put.To package or the suitable arbitrarily time span of bag thermal annealing, about 0.5 minute to about 120 minutes can be comprised.Can anneal to package or bag at the temperature of any appropriate (comprising about 40 DEG C to about 90 DEG C).In some embodiments, at the temperature of 40 DEG C to 90 DEG C, the film of packaging part is annealed.

Desirably, at 70 DEG C, annealing is carried out 25 minutes to package of the present invention or bag.In some embodiments, anneal with the film of time to packaging part of about 0.5 minute to about 60 minutes.In some embodiments, anneal with the film of time to packaging part of about 0.5 minute to about 60 minutes.

embodiment

compare test between embodiment 1-bi-material

Load block and strap is utilized to carry out the test about peeling force to bi-material.First material (" materials A ") is the wrapped product with the surface of being made up of ethylene acrylic, and the second material (" material B ") is the wrapped product with the surface of being made up of LDPE.Fig. 1 shows the paper tinsel film peel test results about this bi-material.

Test 1 inch, sample is wide.By the clip taut band of MTS load block and the end of substrate film.Test is carried out with the speed of 2 feet per minute.Along with sample end is pulled, load rising is until sample is torn and peels off gradually.Start once peel off, according to the local engagement power between strap and substrate film, load is transformable.After medium Opening length, data become more stable, and are averaging test data at the extended distance of 0.75 inch to 1.75 inches.

Then, water contact angle test is carried out on the surface of bi-material.Water contact angle test is performed by the drop utilizing micro pipette to apply 5 microlitres on product.Gather the image of each drop and utilize image procossing to obtain the shape on the surface of each drop, and processing to calculate contact angle to these data.

Film contact angle result shows, the material B with the surface of being made up of LDPE shows the highest contact angle, therefore has the minimum surface energy of tested material.The higher surface energy of materials A (having the surface of being made up of ethylene acrylic) causes the larger trend soaking and stick to for other materials (such as, film band) surface preferably.This is again consistent with the result that observed film band often sticks to materials A.Show result in the following table 1.

table 1 film contact angle result

Two films complete atomic force microscope (AFM) scanning with the physical structure of more understanding each material in depth.Complete three times of each film scanning, one time 100 μm ², one time 25 μm ²with one time 5 μm ².Along with the reduction of scan size, the lateral resolution of image increases, and makes little scan size recognize less feature.Fig. 2 shows the AFM surface RMS roughness of film.

Result shows that materials A demonstrates the highest surfaceness under the identical size scale of 100 square microns, height about 30% more coarse than material B.This and materials A have higher surface energy and the result to the good viscosity of other materials is consistent.Then along with peel test force, Contact-angle measurement and the surface RMS roughness by AFM are measured and can be summed up data, these data all show that materials A wrapping material have the viscosity (peeling force) on higher surface, higher surface energy (lower contact angle) and the higher surface RMS roughness in 100 square micron sample size scales.

These results are with observed often to find that when opening inspection film band adheres to the result of materials A consistent.Think, this trend adhering to materials A with pack in materials A in the trend that cracks of film band directly related.Described result also be seldom found to adhere to material B with observed film band and when being packaged in this material band to experience the result of less stress rupture consistent.Because material B has lower surface energy and roughness, thus when band is packaged enter in this material time, band be not inclined to adhere to or split subsequently.

embodiment 2 – compare test

Manufacture and all comprise the two batch film products of PEO as polymeric constituent, and be packaged in two independently in wrapping material.First wrapping material comprise the internal surface be made up of ethylene acrylic and the second wrapping material comprise the internal surface be made up of LDPE.After 20 weeks, the inspection about stress rupture band is carried out to these batches.

After 20 weeks, first film product be packaged in ethylene acrylic package shows the stress rupture of 30.4%, and first film product be packaged in LDPE package shows the stress rupture of 4.2%.In addition, after 20 weeks, the second batch film product be packaged in ethylene acrylic package shows the stress rupture of 46.4%, and first film product be packaged in LDPE package shows the stress rupture of 0%.

the use of embodiment 3-LDPE wrapping material

Using wherein often a collection of PEO that all comprises to be packaged in the wrapping material comprising the internal surface be made up of LDPE as five batches of mould materials of component of polymer and to place with 36 months stable schemes.Described sample is stored at 25 DEG C or 30 DEG C.When 36 months terminate, the detection about stress rupture is carried out to sample.Present result in table 2 below.

the stress rupture after 36 months is stored under table 2 condition of different temperatures

Lot number	Sample number	Storing temp (DEG C)	There is the per-cent of stress rupture
				1	25	25	0％
2	25	25	0％
				3	25	25	0％
4	25	25	0％
				5	25	25	0％
1	25	30	0％
				2	25	30	0％
3	25	30	0％
				4	25	30	0％
5	25	30	0％

the use of embodiment 4-LDPE wrapping material

Manufacture the film (each is all containing PEO) of nine batches of three kinds of varying strengths and be packaged in the wrapping material with the internal surface be made up of LDPE.After 5 months, the inspection about stress rupture is carried out to film.In with following table 3, result is shown.

the incidence of stress rupture in table 3 experimentai batches

Batch	There is the per-cent of crackle
		1	0％
2	0％
		3	0％
4	0％
		5	0％
6	0.67％
		7	0.20％
8	0％
		9	0％

embodiment 5 – compare test

12 batches of films (each all comprises PEO as component of polymer) are packaged in the wrapping material with the internal surface be made up of ethylene acrylic, and 33 batches are packaged in the wrapping material having and be made up of LDPE.After 3 weeks, the inspection about stress rupture is carried out to film.Then 2 side inspections are utilized to compare two groups of films.Show result in table 4.The p value of 0.005 shows that data set belongs to the high probability of different group film.

table 4 is about overall test result

embodiment 6 – compare test

Using the sample packaging from the film (all comprising PEO as component of polymer) of 22 batches in the wrapping material comprising the internal surface be made up of ethylene acrylic, and using the sample packaging from the film (all comprising PEO as component of polymer) of 32 batches in the wrapping material comprising the internal surface be made up of LDPE.In the different time, film is checked after packaging.Figure 3 illustrates data.In order to more clearly distinguish the ratio of stress rupture time in early days, the second line (Fig. 4) shows 60 days data obtained afterwards.

embodiment 7

Film band is packaged in individually in the bag of paper tinsel/pet layer conjunction.By in the annealing furnace that the sealing bag of product is placed on 70 DEG C, thermal annealing is carried out 25 minutes to some products.Then along with the time carries out the inspection carrying out about stress rupture to product.Each week (after packaging) is opened 2000 samples and checked.Show result in table 5.

the comparison of table 5 stress rupture in annealed film and unannealed film

	2 weeks	3 weeks	4 weeks
				Batch A, unannealed	0.9％	3.3％	4.0％
Batch A, annealing	0.00％	0.00％	0.00％
				Batch B, unannealed	1.0％	8.4％	5.7％
Batch B, annealing	0.25％	0.00％	0.00％

According to the data in table 5, obviously compared with annealing product (presenting substantially unstressed breaking or few stress rupture), unannealed material as one man has more stress rupture.

embodiment 8

Hinds Near-infrared Double dioptric system is utilized to utilize the measurement wavelength inspection of 1310 nanometers to be packaged in the independent film band in new (1 week age) and old (3 monthly ages) in paper tinsel/pet layer conjunction bag.This wavelength shockingly shows anisotropy and isotropic change and other double refraction instrument and wavelength components can not see any double refraction.As (pushed up: new according to annealing more shown, the end: old) before 2D double refraction figure and the 2D double refraction figure after annealing shown in fig. 8 (push up: new, the end: old) be apparent that and locate the surprising minimizing completely that result in stress of mild heat 1 hour at 70 DEG C.Yellow area and red area show higher internal stress and blueness shows minimum stress.According to this experiment apparently, film old before annealing process and new film present internal stress and thermal annealing reduces the internal stress of new sample and old sample.

embodiment 9

Film according to the present invention is applied on substrate and according at United States Patent (USP) the 7th, 425, No. 292, the 7th, 666, No. 337 and the 7th, method disclosed in 357, No. 8912 carries out drying.Before and after, during tearing, film is peeled off from substrate continuously, be heated to annealing temperature, preferably 70 DEG C (scopes of 40 DEG C to 90 DEG C) continue 10 minutes (scopes of 0.5 minute to 60 minutes) and are again wound on substrate.Then film carried out cutting and on the packaging machine of standard, film be packaged in the wrapping material of any type.

Claims (43)

1., for a bag for storage films, comprising:

The laminate of at least one the first layer and at least one second layer; With

Comprise the chamber of film, described film is through annealing with the stress rupture reducing described film, and described film comprises at least one polymkeric substance and at least one active ingredient,

Wherein compared with unannealed situation, through annealing when, described film presents less stress rupture.

2. bag according to claim 1, wherein said at least one polymkeric substance is selected from polyethylene oxide, Vltra tears and combination thereof.

3. bag according to claim 1, at least one the first layer wherein said or at least one second layer described comprise Low Density Polyethylene, ethylene acrylic and combination thereof.

4. bag according to claim 1, does not wherein present stress rupture from about 1 month to about 3 years described film or does not substantially present stress rupture.

5. bag according to claim 4, does not wherein present stress rupture from about 1 month to about 2 years described film or does not substantially present stress rupture.

6. bag according to claim 1, wherein said film also comprises the additive being selected from tensio-active agent, softening agent and combination thereof.

7., for reducing a method for stress rupture in film, comprising:

A) film comprising at least one polymkeric substance and at least one active ingredient is provided;

B) anneal to described film the stress rupture reducing described film, wherein said film presents the stress rupture of minimizing due to described annealing.

8. method according to claim 7, wherein said film also comprises the additive being selected from tensio-active agent, softening agent and combination thereof.

9. method according to claim 8, wherein said additive exists with the amount of account for described film about 5 % by weight to about 30 % by weight.

10. method according to claim 7, does not wherein present stress rupture from about 1 month to about 3 years described film or does not substantially present stress rupture.

11. methods according to claim 7, wherein do not present stress rupture from about 1 month to about 2 years described film or substantially do not present stress rupture.

12. methods according to claim 7, wherein anneal to described film by applying heat to described film at the temperature of about 40 DEG C to about 90 DEG C.

13. methods according to claim 7, wherein to described film heating about 0.5 minute to about 60 minutes.

14. 1 kinds for comprising continuously and reducing the method for stress rupture in the film of uniform product, described method comprises the steps:

A) preparation comprises the film forming matrix of solvent, active ingredient and polymer materials;

B) film forming matrix described in curtain coating drying is carried out to form dry film to described film forming matrix; With

C) stress being released through drying process applying is annealed to described dry film.

15. methods according to claim 14, wherein anneal to described film at the temperature of 40 DEG C to 90 DEG C.

16. methods according to claim 14, wherein anneal to described film with the time of 0.5 minute to 60 minutes.

17. 1 kinds for comprising continuously and reducing the method for stress rupture in the film of uniform product, described method comprises the steps:

A () preparation comprises the film forming matrix of solvent, active ingredient and polymer materials;

B film forming matrix described in () curtain coating also carries out drying to form dry film to described film forming matrix;

C described dry film is packaged in bag to form packaged film by (); With

D () anneals to the film through pack the stress being released through drying process applying.

18. methods according to claim 17, wherein anneal to described packaged film at the temperature of 40 DEG C to 90 DEG C.

19. methods according to claim 17, wherein anneal to described packaged film with the time of 0.5 minute to 60 minutes.

20. methods according to claim 14, wherein by described film is removed from substrate, described film annealed and described film recoiled and at substrate, described film is annealed.

21. methods according to claim 20, wherein anneal to described film at the temperature of 40 DEG C to 90 DEG C.

22. methods according to claim 20, wherein anneal to described film with the time of 0.5 minute to 60 minutes.

23. 1 kinds of stress ruptures reduced continuously and uniform film product, wherein said film product is formed by the method comprised the following steps:

A () curtain coating comprises the film forming matrix of solvent, active ingredient and polymer materials;

B () carries out drying to form dry film to described film forming matrix; With

C () is annealed to be released through to described dry film stress that drying process applies thus is formed the film decreasing stress rupture.

24. films according to claim 23, wherein anneal to described film at the temperature of 40 DEG C to 90 DEG C.

25. films according to claim 23, wherein anneal to described film with the time of 0.5 minute to 60 minutes.

26. 1 kinds of stress ruptures reduced continuously and uniform film product, wherein said film product is formed by the method comprised the following steps:

A () curtain coating comprises the film forming matrix of solvent, active ingredient and polymer materials;

B () carries out drying to form dry film to described film forming matrix;

C described dry film is packaged in bag to form packaged film by (); With

D () is annealed to be released through to the film through pack stress that drying process applies thus is formed the film decreasing stress rupture.

27. films according to claim 26, wherein anneal to described packaged film at the temperature of 40 DEG C to 90 DEG C.

28. films according to claim 26, wherein anneal to described packaged film with the time of 0.5 minute to 60 minutes.

29. films according to claim 23, are wherein annealed to described film by following steps: removed from substrate by described film, anneal to described film and recoiled on substrate by described film.

30. films according to claim 29, wherein anneal to described film at the temperature of 40 DEG C to 90 DEG C.

31. films according to claim 29, wherein anneal to described film with the time of 0.5 minute to 60 minutes.

32. films according to claim 23, wherein said film complete flawless after 3 weeks in package.

33. films according to claim 23, wherein said film complete flawless after 2 months in package.

34. films according to claim 23, wherein said film complete flawless after 6 months in package.

35. films according to claim 23, wherein said film complete flawless after 12 months in package.

36. films according to claim 23, wherein said film complete flawless after 2 years in package.

37. films according to claim 23, wherein said film complete flawless after 3 years in package.

38. films according to claim 29, wherein said film complete flawless after 3 weeks in package.

39. films according to claim 29, wherein said film complete flawless after 2 months in package.

40. films according to claim 29, wherein said film complete flawless after 6 months in package.

41. films according to claim 29, wherein said film complete flawless after 12 months in package.

42. films according to claim 29, wherein said film complete flawless after 2 years in package.

43. films according to claim 29, wherein said film complete flawless after 3 years in package.