CN101321511A - Topical film compositions for delivery of actives - Google Patents

Topical film compositions for delivery of actives Download PDF

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Publication number
CN101321511A
CN101321511A CN 200680045517 CN200680045517A CN101321511A CN 101321511 A CN101321511 A CN 101321511A CN 200680045517 CN200680045517 CN 200680045517 CN 200680045517 A CN200680045517 A CN 200680045517A CN 101321511 A CN101321511 A CN 101321511A
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CN
China
Prior art keywords
thin film
film
water
reagent
polymer
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Pending
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CN 200680045517
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Chinese (zh)
Inventor
G·L·迈尔斯
R·H·福兹
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Aquestive Therapeutics Inc
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MonoSol Rx LLC
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Publication of CN101321511A publication Critical patent/CN101321511A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/86—Polyethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0216—Solid or semisolid forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/731—Cellulose; Quaternized cellulose derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q15/00—Anti-perspirants or body deodorants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/02—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings containing insect repellants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/02—Preparations for cleaning the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/06—Preparations for styling the hair, e.g. by temporary shaping or colouring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/12—Preparations containing hair conditioners
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q9/00—Preparations for removing hair or for aiding hair removal
    • A61Q9/02—Shaving preparations
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D17/00—Detergent materials or soaps characterised by their shape or physical properties
    • C11D17/04—Detergent materials or soaps characterised by their shape or physical properties combined with or containing other objects
    • C11D17/041—Compositions releasably affixed on a substrate or incorporated into a dispensing means
    • C11D17/042—Water soluble or water disintegrable containers or substrates containing cleaning compositions or additives for cleaning compositions
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16—Organic compounds
    • C11D3/20—Organic compounds containing oxygen
    • C11D3/22—Carbohydrates or derivatives thereof
    • C11D3/222—Natural or synthetic polysaccharides, e.g. cellulose, starch, gum, alginic acid or cyclodextrin
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16—Organic compounds
    • C11D3/20—Organic compounds containing oxygen
    • C11D3/22—Carbohydrates or derivatives thereof
    • C11D3/222—Natural or synthetic polysaccharides, e.g. cellulose, starch, gum, alginic acid or cyclodextrin
    • C11D3/225—Natural or synthetic polysaccharides, e.g. cellulose, starch, gum, alginic acid or cyclodextrin etherified, e.g. CMC
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/16—Organic compounds
    • C11D3/37—Polymers
    • C11D3/3703—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • C11D3/3707—Polyethers, e.g. polyalkyleneoxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/594—Mixtures of polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2001/00—Use of cellulose, modified cellulose or cellulose derivatives, e.g. viscose, as moulding material
    • B29K2001/08—Cellulose derivatives
    • B29K2001/12—Cellulose acetate

Abstract

The invention relates to the film products and methods of their preparation that demonstrate a non-self-aggregating uniform heterogeneity. Desirably, the films disintegrate in water and may be formed by a controlled drying process, or other process that maintains the required uniformity of the film. Desirably, the films contain a topical active agent.

Description

The topical film compositions of active agent delivery
The cross reference of related application
The application requires the U.S. Provisional Patent Application the 60/742nd of December in 2005 submission on the 6th, No. 776 priority, this application is the U.S. Patent application of submitting on February 14th, 2002 the 10/074th, No. 272 part continues, this application requires the U.S. Provisional Patent Application the 60/328th of submission on October 12 calendar year 2001 again, the priority that No. the 60/386th, 937, the U.S. Provisional Patent Application of submitting in No. 868 and on June 7th, 2002.
Invention field
The present invention relates to rapidly-soluble self-supporting heavy duty film and preparation method thereof.Thin film comprises the part reagent that is evenly distributed in the thin film.
Background of related
Skin is the organ of human body maximum.Usually, skin needs aesthetic nursing to keep kilter, then needs Drug therapy when it shows disease symptoms.The personal care product of topical administration and medicine are well-known part reagent.
A kind of consideration when using the part with reagent is whether these reagent are applied in skin easily.Usually, the part is assigned on finger or the palm from bottle or pipe with reagent, the reuse hands is applied in skin.This just requires consumer to carry bottle or pipe at whilst on tour irrelevantly.Yet some skin nursing products or medicine may not be fit to the specification supply of travelling.And these products exist with liquid, emulsifiable paste or ointment mostly, the thing of may making dirty.
Can adopt thin film to transmit active component such as medicine, medicine etc. as delivery system.Yet conventional films reaches and has run into many rough sledding that it can not be realized by its method for preparing drug delivery system.
The United States Patent (USP) the 4th, 136, No. 145 (" Fuchs ") of expiration of time limit that is combined with people such as the thin film of active constituents of medicine such as Fuchs is described.These thin film can be made sheet, and drying cuts into each dosage then.The Fuchs open source literature has proposed to prepare the method for homogeneous film, comprises water-soluble polymer, surfactant, flavoring agent, sweeting agent, plasticizer and medicine are made up.According to announcement, the softish thin film that these can be mentioned is used for oral, local usefulness or external.The example of the concrete purposes that Fuchs discloses comprises the membranous part that thin film is used for health, comprises oral cavity, rectum, vagina, nose and ear.
Yet, the thin film according to the preparation of Fuchs disclosed method is detected, find that particle aggregation or reunion can take place this class thin film, promptly from reuniting, making them is uneven in essence.This possibility of result is that the method parameter by Fuchs causes, although not open, this method may comprise and adopts long drying time, reunites thereby impel intramolecularly captivation, convection current power, air-flow etc. to form this classes.
The formation of aggregate makes any activating agent of film composition and existence be random distribution.When relating to heavy dose, the minor alteration of film dimensions aspect all can cause the greatest differences of activating agent quantity in the every thin film.If comprise the low dosage activating agent in this class thin film, then some position of thin film might be basically without any activating agent.Owing to diaphragm will be cut into unit dose usually, so some dosage may lack the activating agent that is proposed to be used in treatment or the quantity not sufficient of activating agent.It is deleterious to the patient that the cutting thin film can't obtain highly accurate active dose.For this reason, use the dosage form that forms such as the processing method of Fuchs can not satisfy government or administrative organization such as the United States Federal's FAD (" FDA ") strict standard about the difference of active dose in the dosage form.At present, each worldwide administrative organization all requires the difference of the active dose that exists in the dosage form not surpass 10%.When being used for the thin film based dosage form, in fact be exactly to require activating agent to be present in the thin film equably.
Proposed to cause thin film uneven in the United States Patent (USP) of Schmidt the 4th, 849, No. 246 (" Schmidt ") from agglomeration traits.Schmidt spells out the Fuchs disclosed method can not provide homogeneous film, and recognizes that the generation of non-uniform film has hindered the accurate quantification that is even more important at pharmaceutical field as mentioned above.Schmidt has abandoned providing as single thin film as described in the Fuchs idea of accurate dosage form, replaces by forming plural layers to attempt addressing this problem.And his method is the rapid process of the multistep of increase expense and complexity, does not have feasibility in the commerce utilization.
Other United States Patent (USP) directly seeks to solve the inherent granule of conventional film technique from reuniting and the heterogeneity problem.In overcoming heteropical trial, the United States Patent (USP) 5,629 of Horstmann etc., 003 and the United States Patent (USP) 5,948,430 of Zerbe etc. add other composition, promptly add into gel and polyhydric alcohol respectively, before dry, increase thin film viscosity to make great efforts to reduce the gathering of component in the thin film.The shortcoming of these methods is to need other component, and this will change extra-pay and manufacturing step into.And these two kinds of methods have all been utilized conventional time-consuming drying means, as using drying oven, tunnel dryer (drying tunnel), vacuum desiccator or other similar drying equipment high temperature air bathe.Although used viscous modifier, long-time drying still can impel activating agent and other adjuvant to assemble.This class course of processing is also being emitted and is being made activating agent (be medicine, or vitamin C, or other component) Long contact time moisture and high temperature and its was lost efficacy or even deleterious risk.
Except worrying that itself can not provide homogeneous film the conventional drying method activating agent can be degraded during the long-term contact wetting.Thermo-contact time span [so-called " adding thermal history (heathistory) "] during the conventional processing and mode of heating have a direct impact the formation and the form thereof of gained film product.When needs are fit to the thicker relatively thin film of bound drug activating agent very much, adopt the conventional drying method especially to be difficult to reach homogeneity.Because when drying, film surface does not experience identical external condition simultaneously with thin film inside, so the thicker homogeneous film of more difficult acquisition.Therefore, the observation of the thicker thin film made by the conventional processing method of this class is demonstrated the heterogeneous texture that is caused by convection current and intramolecular force,, need be higher than 10% moisture in order to keep flexible.Free water component president time interference medicament brings potential problems, thereby final products can not be remained as one.
The conventional drying method generally includes the forced hot air that utilization is produced by drying oven, tunnel dryer etc.The difficulty that obtains homogeneous film is directly relevant with the water evaporation process in the rheological equationm of state and the film-forming composition.When aqueous solutions of polymers surface contacted with high temperature gas flow, during by air stove, superficial water evaporated at once, forms thin polymer film or skin from the teeth outwards as film-forming composition.So just sealed surperficial following remaining aqueous film-forming composition, formed barrier one, remaining water must oneself be made great efforts to penetrate this road thin film and could be evaporated, to obtain exsiccant thin film.Along with the lasting rising of the outer temperature of thin film, the following water vapor pressure of film surface increases, and film surface is finally torn on the oriented film surface, makes water vapour dissipation.In case after the water vapour dissipation, described thin polymer film surface can form again, repeats this process, up to the thin film bone dry.Observe, the result that film surface constantly destroys and forms again is " ripple effect ", promptly produces uneven thereby uneven thin film.Usually, look the situation of polymer, the surface makes remaining shipwreck to discharge deadend, makes that drying time is very long, temperature is higher, the power consumption is more.
Other factors as hybrid technology, also plays effect when manufacturing is suitable for commercialization and can obtain the pharmaceutical film of approved by management.Air may be entrained in the compositions between mixing period or during the made membrane afterwards, when at the drying stage transpiring moisture, may in film product, reserve a little spaces like this.Near the described space thin film usually can cave in, and causes the film surface unevenness and causes final film product inhomogeneous thus.Even does not damage in the space in the described thin film that bubble causes, homogeneity still can be influenced.Because the space of described non-uniform Distribution is to be occupied the zone by what film composite occupied under other situation, so this situation also provides non-uniform film.None mentions or proposes to solve scheme by the problem that air caused that enters thin film above-mentioned patent.
Therefore, need a kind of film product compositions and manufacture method thereof, adopt minimum material or composition, in whole thin film zone, provide non-basically from the even heterogeneity of reuniting.Preferably, this film product is applicable to that sending the part uses reagent, thereby is using this product to provide convenience during travel for consumer.
Preferably, this thin film is by selecting to provide the polymer of required viscosity or the combination of polymer to prepare.Also preferably, thin film is by film formation process, and for example reverse roll coating, extruding, casting and controlled desirable rapid draing process prepare, to keep non-uniform distribution from the composition of reuniting.Preferably, preparation process not necessarily needs to add in the product of existing patent and the method the seemingly gellant of essential composition or polyhydric alcohol etc., for example above-mentioned Horstmann and Zerbe patent.Preferably, thin film also comprises the compositions and the manufacture method thereof that can significantly reduce or eliminate the air in the thin film, thereby improves the homogeneity of final film product.
Summary of the invention
The invention provides thin film and forming method thereof.Thin film can be divided into has the equidimension unit of the various constituents of equivalent basically.This advantage is particularly useful, because this allows to form earlier large area film, cuts into individual then and do not need to consider whether each unit equates on forming.For example, thin film of the present invention is particularly useful for the delivery system of Topically active agent, because each film unit comprises the Topically active agent of appropriate amount.
Term used herein " the local reagent of using " refers to contain the activating agent that is applied to certain surface areas.For example, in one embodiment, the part is applied to skin area with reagent.In other embodiments, the part is applied to the health mucosal areas with reagent, for example oral cavity, vagina and anal regions.In other embodiments, the part is applied to hard surface with reagent, for example needs the certain surface areas that cleans.
In one aspect of the invention, provide a kind of self-supporting heavy duty film.This thin film comprises water-soluble polymer composition, comprises poly(ethylene oxide) and glycosyl polymer.Thin film also comprises part reagent.Following described in more detail, preferably when thin film contact wetting agent such as water, dissolve basically.Thin film contact with wetting agent cause local with reagent from Film Fractionation or dispersion.Then the part is applied to certain surface areas with reagent, for example skin area.
The present invention also provides can dissolved basically self-supporting heavy duty film, and it comprises (i) water-soluble polymer composition, and it comprises at least a glycosyl polymer; (ii) shampoo.
Also providing can dissolved basically self-supporting heavy duty film, and it comprises (i) water-soluble polymer composition, and it comprises at least a glycosyl polymer; (ii) hair conditioner (hair conditioner).
Also providing can dissolved basically self-supporting heavy duty film, and it comprises (i) water-soluble polymer composition, and it comprises at least a glycosyl polymer; (ii) sunscreen.
And the present invention also provides can dissolved basically self-supporting heavy duty film, and it comprises (i) water-soluble polymer composition, and it comprises at least a glycosyl polymer; (ii) antibacterial soap.
And the present invention also provides can dissolved basically self-supporting heavy duty film, and it comprises (i) water-soluble polymer composition, and it comprises at least a glycosyl polymer; (ii) anthelmintic.
Also providing can dissolved basically self-supporting heavy duty film, and it comprises (i) water-soluble polymer composition, and it comprises at least a glycosyl polymer; The emulsifiable paste of (ii) preserving moisture.
The present invention also provides can dissolved basically self-supporting heavy duty film, and it comprises (i) water-soluble polymer composition, and it comprises at least a glycosyl polymer; Emulsifiable paste or gel (ii) shave.
And the present invention also provides can dissolved basically self-supporting heavy duty film, and it comprises (i) water-soluble polymer composition, and it comprises at least a glycosyl polymer; (ii) antibiotic.
And also providing can dissolved basically self-supporting heavy duty film, and it comprises (i) water-soluble polymer composition, and it comprises at least a glycosyl polymer; (ii) kitchen detergent (dish detergent).
All thin film of the present invention may be partitioned into less independent film unit, and adjustment size and packing back form dosage unit form and use for consumer.
In another aspect of this invention, provide the method for making the heavy film unit of self-supporting.This method may further comprise the steps: with polar solvent, local with reagent and comprise poly(ethylene oxide) and the water-soluble polymer composition of at least a glycosyl polymer makes up, form the equally distributed material of these components.Make this material filming then and send on the end face of substrate surface with bottom surface and end face.Heating is with dry film on the bottom surface of substrate surface.Then exsiccant divided thin film is slit into independent film unit.
In addition or alternatively, except the ad hoc approach that dry film adopts, also can realize to keep the evenly heterogeneous viscosity of non-self aggregation by selective polymer.Can be used for film forming technology and comprise that also reverse roll is coated with, to push, deposit to mould medium.
The allotter that comprises independence film unit of the present invention also is provided.This film unit can randomly be stacked in allotter or the roller.
Another aspect of the present invention provides sends the part compositions and methods.This method comprises: dry film is provided, dissolves at least in part during this thin film moistening, this thin film comprises (i) water-soluble polymer composition, and it comprises poly(ethylene oxide) and glycosyl polymer; (ii) part reagent.This method also comprises to be made thin film contact with wetting agent and makes the local agent dissolves of using; Dissolved part need to be applied to local surf zone with reagent with reagent.
The present invention also provides and has been used to apply local system with reagent.This system comprises and local uses reagent that this part is contained in the soluble polymeric films that contains poly(ethylene oxide) and glycosyl polymer with pack.This system also comprises the solvent that is used for dissolving films.Solvent directly contact with thin film and cause local with reagent from thin film stripping or dispersion, thereby the local surf zone that needs of can be applicable to reagent.Randomly, system also comprises the applicator that is used for the part is applied to reagent the surf zone of needs.
Others of the present invention relate to the thin film that is used to send emulsion composition.For example, the invention provides a kind of compositions, it comprises the water-soluble polymer solid matrix; And the multiple lipotropy drop that is dispersed in the substrate, when contacting water, described compositions forms liquid/liquid Emulsion.
The self-supporting heavy duty film that is used to send liquid/liquid Emulsion also is provided.Thin film comprises the solid, water soluble polymeric matrix, wherein is dispersed with the multiple lipotropy drop that is formed by emulsion composition.
The present invention also provides the method for preparing emulsion composition.
A kind of method for preparing emulsion composition comprises: water-based emulsions is provided; Water-based emulsions is converted into non-water base dried breast, and described dried breast is the form of self-supporting heavy duty film.This method also comprises use dissolution with solvents thin film, forms water-based solvent again.
The another kind of method for preparing emulsion composition comprises: the water-soluble polymer that wherein is dispersed with many lipotropy drops solid film is provided; Add entry with dissolving films, thereby form Emulsion.
And, the invention provides the method that preparation is used for the thin film of active agent delivery.This method comprises: the preparation compositions, and said composition comprises at least a water-soluble polymer, polar solvent and contains the emulsion composition of activating agent; And composition forming film from preparing.This method also comprises by certain method dry film, thereby the many lipotropy drops that comprise activating agent is disperseed from thin film.
Also provide preparation can be under the water effect method of the emulsion composition of reconstruct.This method comprises the preparation compositions, and said composition comprises at least a water-soluble polymer, polar solvent and emulsion composition.This method also comprises carries out drying with compositions, is dispersed in dried breast in the water-soluble polymer solid matrix to form the lipotropy drop.
The present invention also provides the method for sending emulsion composition.This method comprises provides the solid aqueous that wherein is dispersed with many lipotropy drops polymeric matrix.This method also comprises makes polymeric matrix contact with the dissolve polymer medium with wetting agent, thereby forms Emulsion; Emulsion is applied to the surf zone of needs.
Another aspect of the present invention relates to the system that is used to apply Emulsion.This system comprises does breast, and dried breast comprises lipophilic liquid and is scattered in wherein soluble polymeric films.This system also comprises the solvent that is used for dissolving films.Solvent directly contacts with doing breast, causes doing newborn reconstruct, thereby the Emulsion of reconstruct is applied to the surf zone of needs.Randomly, system also can comprise the applicator that is used for the Emulsion of reconstruct is applied to the surf zone of needs.
Another aspect of the present invention relates to and is applicable to the compositions of sending the eutectic composition dispersion.For example, the invention provides a kind of compositions, it comprises the water-soluble polymer solid matrix; And many eutectic compositions drops that are dispersed in the described substrate, when contacting water, described compositions forms the eutectic composition dispersion.
Brief Description Of Drawings
Fig. 1 shows the side view of the packing that contains unit dose thin film of the present invention.
Fig. 2 shows two top views in abutting connection with packing that contain individual dosage form of the present invention, and they are by can bursting perforatedly separating.
Fig. 3 shows the side view in abutting connection with packing shown in Figure 2 with stacking construction.
Fig. 4 shows the perspective view of the allotter be used to distribute described packaged unit dosage forms, and allotter contains the encapsulation unit dosage forms with stacking construction.
Fig. 5 is the sketch map of the unit dose packaging of a volume connection of the present invention.
Fig. 6 is suitable for being pre-mixed, adding activating agent, the sketch map of film forming manufacturing equipment then.
Fig. 7 is the sketch map that is suitable for the equipment of dry thin film of the present invention.
Fig. 8 is the successive views of dry run of the present invention.
Fig. 9 is the sketch map of the continuous regional drying equipment that connects according to the present invention.
Figure 10 is the sketch map of the distinct area drying equipment according to the present invention.
Detailed Description Of The Invention
For purposes of the present invention; term " non-from assembling even heterogeneous property " refers to the performance of film of the present invention; described film adds that by one or more components polar solvent forms, and can significantly reduce the phenomenon that component is assembled or reunited in the film that (be rare or do not occur fully) can experience when forming film usually with conventional drying method (as adopting high temperature air bath, tunnel dryer, vacuum desiccator or other this type of drying equipment of drying oven). The term " heterogeneous property " that the present invention adopts comprises in conjunction with one-component such as polymer, and the film of the combination of each component such as polymer and activating agent. " even heterogeneous property " comprises gathering or the reunion that usually can occur when basically not adopting conventional mixing and heated drying method to form film.
And the thickness of film of the present invention is basically consistent, and this also is that conventional drying method for drying water based polyalcohol system can not provide. Can't obtain the harmful impact of homogeneity generation that consistent thickness distributes in given film zone on component.
With producing film product of the present invention through polymer, polar solvent and the part of suitably selecting with the combination of reagent and other fillers as known in the art. By adopting selected casting or deposition process and controlled drying means, the component in these films has non-from assembling even heterogeneous property. The example of controlled drying means includes but not limited to: the United States Patent (USP) the 4th that uses Magoon, 631, disclosed equipment in No. 837 (" Magoon ") (it is for referencial use to include in full this paper in it), and the hot-air impingement flow is through bottom and bottom-heated dish. The dry technology that another kind is used for acquisition film of the present invention is not have the not controlled radiant drying of controlled airflow, such as infrared ray and radio frequency radiation (being microwave).
The purpose of described drying means provides the film drying method of can avoid purposely causing complication (such as famous " ripples (rippling) effect "), the described problem that purposely causes complication is relevant with the conventional drying method, it is the upper surface of dry film at first, and the result makes moisture retention in inside. In the conventional oven drying means, when the moisture that is trapped in inside evaporated in the back, end face can change because being torn, and then again formed.
The present invention has avoided these complicated processes, by the bottom surface of first dry film or avoided top surface to form polymer film (skin) before the dry film depths providing homogeneous film. This can realize in the following manner: to film bottom surface heating and the top there is no air-flow; Perhaps adopt control microwave to come thin evaporated film interior moisture or other polar solvent, same, the top there is no air-flow.
Perhaps, can realize drying such as the balance air-flow by adopting balanced fluid stream, wherein bottom and top stream are controlled, and homogeneous film is provided thus. In this case, the described air-flow that points to the film top should not can cause following problem: because the active force that air-flow produces, the particle that exists in the wet film is moved.
In addition, the air-flow that points to the film bottom is preferably controlled, thereby makes the film can the lifting because of the active force of air-flow. Not controlled airflow above or below the film can cause final film product inside inhomogeneous. Regional humidity level prevents the too early closure of polymer surfaces or skinning around can also suitably regulating end face.
This kind film drying method has a plurality of advantages, and comprising faster drying time and more uniform film surface, and each component evenly distributes in any given area of film. In addition, faster drying time can be in film very fast generation viscosity, further support each component evenly to distribute and reduce the gathering of each component in the final film product. Ideally, the drying of film is at about 10 minutes or shorter or betterly carry out in about 5 minutes or shorter time.
If focus is placed on the cohesion that reduces each component of composition, the present invention can produce especially uniformly film product. If in mixed process, avoid introducing and in time disposing excessive air, select polymer and solvent that controlled viscosity is provided, and by upwards film being carried out drying from the bottom fast, then can obtain this class film.
Product of the present invention and method rely on each production stage of described film to cooperatively interact to provide the film from the remarkable minimizing of clustering phenomena of each component in the film. Particularly, these steps comprise concrete film build method, prevent from carrying secretly the air inlet bubble composition mixture preparation method, be controlled to method and the film drying method of the viscosity of film composition. More specifically, in order to prevent surfactant precipitate, when described activating agent was insoluble to selected polar solvent, component of mixture viscosity was higher then especially useful. Yet to such an extent as to viscosity can not too highly hinder or hinder the selected casting method that waters, described method preferably includes and reverses roller coat cloth, and this is because it can provide basically consistent film of thickness.
Except film viscosity or film-forming components or matrix, the present invention needs also to consider that other factors just can reach required film homogeneity. For example, obtained to prevent that solid (such as drug particles) from the stable suspersion liquid of precipitation occuring in non-colloid is used. A kind of method provided by the invention is to make particle density (ρp) and liquid phase density (ρ1) reach balance and increase the viscosity (μ) of liquid phase. With regard to the particle that separates, as follows about the Stokes law (Stokes law) of the final settling velocity (Vo) of rigid spheres in the viscosity fluid of certain radius (r):
V o＝(2gr r)(ρ p-ρ 1)/9μ。
Yet when granule density is high, local granule concentration will affect local viscosity and density. The viscosity of suspension is the majorant (strong function) of fractional solid volume, and particle-particle and particle-liquid interacts will further hinder settling velocity.
The Stokes analysis shows, adds third phase, such as air or the nitrogen that disperses, the stability that can promote suspension. In addition, the increase amounts of particles can produce the precipitation of being obstructed based on fractional solid volume. In rare particle suspension liquid, settling rate v can be expressed as:
Figure A20068004551700201
Wherein κ is a constant,It is the volume mark that disperses phase. The particle that is suspended in the liquid phase is more, and speed is lower. Because the particle size can affect the mobile mutual effect of particle-particle, so the particle geometric shape also is an important factor.
Similarly, the viscosity of suspension depends on the volume mark of dispersing solid. With regard to regard to rare suspension of the spherical particle of mutual effect, the viscosity of suspension can be expressed as:
μ/μ o＝1+2.5φ
μ whereinoBe the viscosity of continuous phase, φ is fractional solid volume. When the volume mark was higher, the viscosity of dispersion can be expressed as:
Figure A20068004551700203
Wherein C is constant.
The viscosity of liquid phase is very crucial, preferably by the customization fluid composition liquid improvement is hanged down the viscoplasticity non-newtonian fluid of surrendering the stress value for having. This and the static continuous equivalent of generation high viscosity. The fluid of formation viscoplasticity or highly structural is on good terms provides additional friction for particle precipitates. In addition, make particle-Interaction between particles drop to low energy control flocculation or assemble. Net effect is kept even decentralized photo exactly.
Aqueous phase toward suspension adds glue physical efficiency increase viscosity, can produce viscoplasticity, and based on different glue body types, its concentration and particulate composition, geometry, size and volume mark, can give stability. Need to control the size distribution in the decentralized photo by selecting the minimum actual granularity in the high viscosity medium to be＜500 microns. No matter apparent viscosity how, exist the elastomer of slight surrender stress or low shear rate also can bring lasting stability. Can calculate the critical particle diameter by surrender stress value. In spherical particle situation separated from one another, the maximum shear stress that precipitation produces in the medium of given viscosity is as follows:
τ Maximum＝3Vμ/2r。
With regard to pseudoplastic fluid, just in time be zero shear viscosity characterization on newton's platform (Newtonian plateau) in the viscosity under this shear state.
To inject the premix compositions of film cast machine for preparation, and keep the stability of wet pellicular stage until fully dry with locking particle and matrix, thereby make it fully form solid form and keep homogeneity, stable suspension is an important characteristic. With regard to viscoelastic fluid system, the rheology that can obtain long-time as 24 hours stable suspersion liquid must balance each other with the demand to the high-speed film pouring operation. Desirable film should have rareization of shearing or pseudoplastic characteristics, and thus, viscosity can reduce with the increase of shearing speed. Time dependence shearing effect for example thixotropy also is favourable. Structure recovery and to shear rareization behavior be important characteristic, film has the ability no less important that the oneself evens up when forming.
The rheology condition of the present composition and film is very strict. This is because of the stable particle suspension liquid of generation, for example particle suspension liquid of 30-60 % by weight in the viscoelastic fluid matrix that need to all have the acceptable viscosity value in large range of shear rate. May experience 10-10 between mixing, suction and film casting cycle5Second-1Shearing speed, pseudoplastic behavior is preferred embodiment.
When film cast or coating, in order to form the film with required homogeneity, rheology also is a restriction factor. Shear viscosity, stretching viscosity, viscoplasticity, structure restoring force can affect the quality of film. The illustrative example of evening up the pseudoplastic fluid of shearing rareization is as follows:
α (n-1/n)＝α o (n-1/n)-((n-1)/(2n-1))(τ/K) 1/n(2π/λ) (3+n)/nh (2n+1)/nt
Wherein α is the surface wave amplitude, α oBe initial amplitude, λ is the wavelength of surface roughness, and " n " and " K " all is viscosity power law index.In this example, it is relevant with viscosity to even up character, with the reducing and increase of n, reduces with the increase of K.
Ideally, thin film of the present invention or film-forming composition can very fast recovery structures, that is, behind treated formation thin film, it can disintegrate or is becoming discontinuous aspect its structure and the component homogeneity.This structural fast quick-recovery can slow down solids precipitation and deposition.And thin film of the present invention or film-forming composition are preferably the pseudoplastic fluid of shear thinning.If with due regard to arrive various character, for example viscosity and elasticity, this class fluid can promote the formation and the homogeneity of thin film.
Therefore, the homogeneity of component mixture depends on many variablees.As described herein, the rheological behavior of the viscosity of described component, hybrid technology, the blend compositions that makes and wet casting thin film all is an importance of the present invention.In addition, also to further consider controlling particle size and grain shape.Ideal particle size is 150 microns or littler, for example 100 microns or littler.And this class granule can be spheroidal particle, granule or aspherical particle spherical in shape substantially, as erose granule or oval granule.It is desirable to oval granule or ellipsoid granule, lower because sedimentary tendency takes place for they than the precipitation of spheroidal particle tendency, thereby can be maintained in the homogeneity of membrane matrix.
Can adopt many technology to prevent from final thin film, to carry bubble secretly at mix stages.In order to be provided at the composition mixture that does not have bubble formation in the final products basically, can adopt anti-foaming agent or surface tension reducer.In addition, preferably can also control mixing velocity, prevent from gas inspiration mixture is formed cavitation.At last, can also make bubble overflow by before dry film, mixture being left standstill the sufficiently long time, to reduce bubble.Ideal the inventive method is at first to form the film-forming components masterbatch that does not contain active component such as drug particles or volatile material such as flavored oils.In one embodiment, before being about to pour into a mould, described activating agent is added in the less masterbatch mixture.Therefore, described masterbatch premix can leave standstill the long period and need not to consider the unstability of activating agent or other composition.
When formation contains film forming polymer and polar solvent, when also having the substrate of other additive and active component in addition, can finish through many steps.For example, whole compositions can be added together or can prepare premix.The advantage of premix is that all the components except activating agent can make up in advance, is being about to just to add activating agent before the film forming.This activating agent that can degrade to Long contact time water, air or another kind of polar solvent is even more important.
Fig. 6 has shown a kind of be suitable for preparing premix, adding activating agent and film forming subsequently equipment 20.The described premix or the masterbatch 22 that will comprise film forming polymer, polar solvent and any other additive except that activating agent add masterbatch feed well 24.Preferably in the blender (not shown), form each component of premix or masterbatch 22, and then add in the masterbatch feed well 24.Then, the masterbatch with scheduled volume controlledly adds first and/or second blender 30,30 ' through first dosing pump 26 and control valve 28.Yet the present invention is not limited to adopt two blenders 30,30 ', can adopt any amount of blender suitably.And the present invention is not limited to blender 30, any particular sorted of 30 ', parallel connection ordering as shown in Figure 6, but can adopt other ordering or arrangement to blender suitably, and as series connection, perhaps in parallel and placed in-line combination.The activating agent of aequum or other composition are added in the required blender by each blender 30,30 ' opening 32,32 '.Preferably make premix or masterbatch 22 holdup time in blender 30,30 ' the shortest.Although activating agent is disperseed in premix or masterbatch 22 fully, the long holdup time can make activating agent leach or dissolving, and is especially true to the soluble agents activating agent.Therefore, blender 30,30 ' is littler than the elementary blender (not shown) that is used to form premix or masterbatch 22 usually, can shorten the holdup time.Activating agent mixes the sufficiently long time with the masterbatch premix, obtain even substrate after, with a certain amount of even substrate through second dosing pump 34,34 ' deliver to the dish 36 on.Described metering roll 38 has determined the thickness of thin film 42, and it is delivered to application roll.Final described thin film 42 is shaped on base material 44, transports through backing roll 46.
Though the appropriate viscosity homogeneity of mixture and stable particle suspension and pouring procedure in the initial step that forms compositions and thin film to promoting that homogeneity is very important, yet it is important too that wet thin film is carried out exsiccant method.Although these parameters and characteristic help initial homogeneity,, when controlled quickly drying method can guarantee to make homogeneity remain to film drying.
Then, preferably under the condition that does not have outer gas stream on the end face (exposure) 48 of thin film as described herein or it is not heated, adopt the dry or controlled method for microwave drying dry wet thin film in controlled bottom.Dry or the controlled microwave drying in controlled bottom can advantageously make the thin film released vapour and avoid the shortcoming of prior art.The conventional convection current air drying that begins from the top can make thin film begin drying from topmost, hinders fluid together as the steam of evaporation and the mobile barrier of hot-fluid such as dry heat energy thereby form, thereby can not adopt.The exsiccant top section of this class constitutes barrier, hinders the further release of steam when dry bottom portion, thereby obtains the heterogencity thin film.As mentioned above, some top stream can be with helping dry thin film of the present invention, but it necessarily can not cause a kind of like this situation, causes in thin film that promptly granule moves and/or ripple effect, thereby causes heterogencity.If adopt the top air, it must balance each other with the bottom air drying, avoids heterogencity and prevent that thin film from arching upward on transport tape with this.When the bottom air-flow plays main dry source, and top stream plays the time spent of doing of less important dry source, and top and bottom air-flow be balance suitably.The advantage that some top stream are arranged is to take away the steam of discharge from thin film, thereby helps whole dry run.Yet the exsiccant utilization in any top stream or top all needs the many factors of balance, includes but not limited to: the rheological characteristic of compositions and the mechanical factor in the processed.The intrinsic viscosity of film-forming composition as described in any top fluid stream (as air) all can not weaken.In other words, described top stream can not be destroyed, be twisted or the surface of the described compositions of Physical Interference otherwise.And air velocity preferably is lower than the yield value of thin film,, is lower than any level of force that can be moved into the liquid in the film composition that is.With regard to thin or low viscous compositions, must adopt low-flow speed.With regard to stiff or full-bodied compositions, can adopt higher air velocity.And air velocity is preferably lower, thereby avoids the thin film made by compositions that any arch upward or other moves taken place.
And thin film of the present invention can contain the temperature sensitivity granule, as volatile ingredient, or the medicine with low degraded temperature.At this moment, can reduce baking temperature, prolong drying time simultaneously, with intensive drying homogeneous film of the present invention.And, to compare with the top drying, the bottom drying also can make the temperature in the thin film lower.Compare with the top drying, carry out the bottom when dry, the steam of evaporation can be more easily with heat band scrapping off film, thereby reduces temperature in the thin film.The interior temperature of the thin film that this class is lower can reduce the degraded of medicine usually, reduces the loss of some volatile ingredient such as flavoring agent.
During the preparation thin film, preferred dry film at high temperature.High temperature drying produces homogeneous film, and film preparation efficient is higher.Yet the thin film that contains the sensitivity active component at high temperature may face woods degradation problem.Degraded is meant " compound decomposition ... produce the intermediate product of determining " [" U.S.'s tradition English dictionary " (TheAmerican Heritage Dictionary of the English Language, the 4th edition, 2000)].The degraded of active component does not wish normally to take place that it can cause unstable active components, inactivation and/or render a service and reduce.For example, if active component is medicine or bioactive substance, this may cause harmful effect to the safety or the effectiveness of final drug products.In addition, when adopting the conventional drying method, the height volatile material tends to discharge from thin film fast.
The degraded of active component can take place by number of ways, and for example hydrolysis, oxidation and photodegradation specifically depend on specific active ingredient.And temperature has appreciable impact to the speed of above-mentioned reaction.10 ℃ of the every increases of typical temperature, degradation rate doubles.Therefore, think all generally that active component is exposed to high temperature will cause and/or quicken not wish the degradation reaction that takes place.
Protein is the useful part activating agent of a class, and they are exposed to for a long time, and high temperature may be degraded, degeneration or inactivation.Protein has multiple function in vivo, for example enzyme, construction unit, hormone or immunoglobulin.Proteinic example comprises: enzyme, for example pancreatin, trypsin, pancreatic lipase, Chymotrypsin, hyaluronidase, sutilains, streptokinase, urokinase, alteplase (altiplase), papain, bromelain, amylase; Construction unit, for example collagen, elastin or albumin; Hormone, thyroliberin for example, gonadoliberin, thyroliberin, thyroliberin, cosyntropin, somatrem, growth hormone, prolactin antagonist, thyrotropin, somatostatin, vassopressin, felypressin, lypressin, insulin, glucagon, gastrin, pentagastrin, secretin, CCK PZ, and immunomodulator, it also can comprise polysaccharide except that glycoprotein, comprise being applicable to inhibition or preventing the malignant cell growth, as the cytokine of tumor growth.The method that is fit to the useful glycoprotein of preparation is referring to the United States Patent (USP) 6,281,337 of Cannon-Carlson etc., and its content is introduced in this description in the reference mode.
Peptide is another kind of useful part activating agent, and Long contact time high temperature may inactivation.For example, can comprise peptide in the skin nursing products.
Usually will cause protein, some peptide and nucleolysis near 100 ℃ temperature.For example, if continue to place 30 minutes under 70 ℃ temperature, some glycoproteins will be degraded.Known protein from the cattle extract is also degraded under this temperature.DNA also begins degeneration under this temperature.
Yet the applicant finds, thin film of the present invention can contact high temperature and the degraded, loss of activity or the excessive vaporization that do not need to consider to cause in film preparation and the forming process in dry run.Specifically, thin film can be exposed to the temperature that will cause active component degraded, degeneration or inactivation usually, and can not produce the problems referred to above.According to the present invention, the may command drying mode arrives active component with the heat of avoiding harmful degree.
As described herein, but according to the uniform flowing mixture of content preparation of the present invention.Forming at flowable mass must the maintenance homogeneity between thin film and dry period.In the dry run of the present invention, some factors cause producing homogeneity in the thin film, active component are maintained under the safe temperature simultaneously, promptly are lower than its degradation temperature.At first, the heat time heating time of thin film of the present invention is extremely short, has only a few minutes usually, thereby shortens total temperature time of contact as far as possible.Dry film controlledly preventing that each component from reuniting and migration, and prevents that internal heat from gathering.Preferably, from the bottom dry film.As described herein, controlled bottom drying can prevent to form thin polymer film or skinning on top surface.When heat upwards conducted bottom thin film, liquid-carrier such as water migrated to film surface.Owing to do not have surface skining, liquid-carrier is rapid evaporation with the rising of temperature, and the evaporative cooling of thin film takes place simultaneously.Since during thermo-contact short between and be subjected to the evaporative cooling effect, thin film composition such as medicine or volatility activating agent are not subjected to temperatures involved.On the contrary, skinning can be held back the liquid-carrier molecule that the thin film self-energy raises on the end face, causes the interior temperature rising of thin film and active component is exposed to having the high temperature of potential hazard.
Secondly, because the bottom is heated and do not had surface skining, the heat mixing takes place in the thin film.The heat mixing takes place by the convection current in the thin film.To thin film when heating bottom, near the temperature of liquid the bottom raises, and expands and density reduces.Like this, the liquid of heat is to rising and colder liquid replaces its position.When rising, heat promptly takes place and shifts in the liquid of heat and colder liquid mixing and heat shared with it.Along with circulation repeats, heat is distributed in the whole thin film.
The potent heat that the controlled dry run of the present invention is realized is blended in and has produced uniform thermal diffusion in the whole thin film.If there is no this heat is mixed, and then " focus " may occur.Heat bag in the thin film can cause the formation of thin film endoparticle aggregation or deathtrap, thereby causes inhomogeneity.The formation of this aggregation or aggregate is disadvantageous, because this can cause the heterogencity thin film of active component random distribution.This inhomogeneity distributes and may cause the active agent content in the every thin film to have significant difference, causes the problem of safety and effectiveness aspect.
And heat is mixed with and helps keep bulk temperature lower in the thin film.Though film surface may be exposed to the temperature above the active component degradation temperature, the thin film inwall may not reach this temperature.Because this temperature contrast, activating agent is not degraded.
For example, preferably with film drying of the present invention 10 minutes or time still less.With film drying 10 minutes, the temperature contrast of generation was about 5 ℃ under 80 ℃.This just means that after dry 10 minutes, the temperature in the thin film is lower 5 ℃ than outer exposed temperature.Yet, in many cases, less than 10 minutes drying times enough, for example 4-6 minute.The dry temperature contrast of following in 4 minutes is about 30 ℃, and dry 6 minutes, temperature contrast was about 25 ℃.Because this big temperature contrast, thin film is efficient drying and do not cause the degraded of heat sensitivity activating agent at high temperature.
Fig. 8 is the successive views of dry run of the present invention.After the mechanical mixture, carry out on the blended conveyer belt of Continuous Heat during thin film is placed at dry run.When dry run begins, shown in the A district, (not shown) when thin film 1 is advanced by conveyer belt, preferably 10 heating thin film from the bottom.Heat can offer thin film by heating arrangements, such as but not limited to drying machine shown in Figure 7.Along with the rising of film temperature, liquid-carrier or volatile material (" V ") start vaporizer, as shown in arrow 50.Along with than hot liquid to rising (shown in the arrow 30), and colder liquid replaces its position (shown in the arrow 40), has also just started hot mixed process.Because the end face 20 of thin film 1 does not form skinning, shown in the B district, so volatile liquid continues evaporation 50, and heat mixing 30/40 continues to allow heat be distributed in the whole surface.After the evaporation of volatile liquid of q.s, heat is blended in and produces uniform thermal diffusion in the whole thin film 1.Gained dry film 1 is a viscoelastic solid, shown in the C district.Each composition is locked in the thin film ideally and is evenly distributed.Though behind the formation viscoelastic solid, may still leave small amount of liquid carrier (being water), when needing, thin film can obtain further dry and particulate moving can not taken place.
And, can also after the casting of compositions or mixture is formed thin film, granule or microgranule be added in described film-forming composition or the substrate.For example, can be before dry film 42 granule be added thin film 42.Can controlledly granule be added on the thin film with metering method, be placed on the thin film, granule controlledly is deposited on the film surface as the scraper (not shown) device of touching or touch film surface by utilization gently at the edge by suitable technique.Other suitable but nonrestrictive technology comprises: utilizes and extends roller granule is placed on the film surface, and particle jetting is first-class to film surface.Described granule can be placed on the one or both sides of film surface, i.e. the end face of film surface and/or bottom surface.Preferably, granule firmly is arranged on the thin film, as embedding in the thin film.And preferably, this class granule is fully embedding or embed in the thin film fully, but still is exposed to film surface, as is partially submerged into or the situation of part embedded particles.
Granule can be any useful part reagent.Useful part comprises personal care product and medicine with reagent.In some embodiments, locally be selected from reagent: soap, body detergent, shampoo, hair conditioner, hairspray (hair stying agent), wetting agent, oxter deodorizer and/or Antiperspirant, emulsifiable paste or gel, sunscreen and anthelmintic shave.In other the embodiment, the part can be selected from reagent: the medicine and the anesthetis of antibacterial, acne medicine, hormone, prevention motion sickness, for example prilocaine, lignocaine and their combination at some.
Although the inventive method is not limited to any above-mentioned preferable exsiccant concrete instrument that can be used for, a kind of concrete useful drying instrument 50 as shown in Figure 7.Drying instrument 50 is the nozzle arrangement that hot fluid (such as but not limited to hot-air) guiding are positioned at thin film 42 bottoms on the base material 44.Hot-air enters the entrance point 52 of described drying instrument, moves toward air deflector 56 vertically upward shown in vector 54.Described air deflector 56 changes the direction that air moves, and makes the upward force minimum to thin film 42.As shown in Figure 7, when air flow through air deflector 56, enter and when the chamber portion 58 of the described drying instrument 50 of flowing through and 58 ', air is oriented in a tangential direction mobile shown in vector 60 and 60 '.The thermal current direction is tangent with thin film 42 basically, thereby the probability that thin film arches upward when making drying reduces to minimum.Although illustrated air deflector 56 is rollers, also suitable preferred other device and the geometry of adopting come local derviation air or hot fluid.And the port of export 62 and 62 ' of described drying instrument 50 opens downwards.This opening downwards provides as vector downward power shown in 64 and 64 ' or downward velocity vector, thereby helps to provide tractive or drag interaction to thin film 42, prevents that thin film 42 from arching upward.Arching upward of thin film 42 not only can cause heterogeneity in thin film, and when thin film 42 and/or base material 44 from process equipment arch time-out, can not be controlled to the processing of thin film 42.
Monitoring and control film thickness can provide thickness uniform thin film, thereby also help to produce homogeneous film.The thickness of thin film can be monitored with gauge such as beta thickness gauge (Beta Gauge).Gauge can be the terminal coupling of drying oven or tunnel dryer at drying instrument with another gauge, is communicated with the opening of controlling and regulate applicator through feedback circuit, thus the homogeneity of control film thickness.
Usually polymer and polar solvent of suitably selecting by the combination warp, and required any active component or filler prepare described film product.Preferably, the solvent in the combination account for total combination at least about 30 weight %.Preferably by roller coat the substrate that this is combined to form being made thin film, preferably carry out drying by quick and controlled drying means then, to keep the homogeneity of thin film, more specifically say, is that non-self aggregation is evenly heterogeneous.The thin film that obtains preferably contains the following solvent of 10 weight % of having an appointment, the solvent that more desirably about 8 weight % are following, even following solvent and the following solvent of most desirably about 2 weight % of more desirably about 6 weight %.Described solvent can be water, polar organic solvent, includes but not limited to: ethanol, isopropyl alcohol, acetone, dichloromethane or its any combination.
To above-mentioned parameter, also can influence the material selection of different component of the present invention such as but not limited to the consideration of rheological characteristic, viscosity, mixed method, casting method and drying means.And the consideration that this class is selected suitable material makes the present composition, comprises in medicine and/or beauty treatment dosage form or the film product that the medicine in the per unit area and/or the difference of cosmetic activity agent are no more than 10%.In other words, be no more than 10 weight % by the difference that makes the medicine that exists in the whole substrate and/or cosmetic activity agent and determine homogeneity of the present invention.Ideally, described difference is below the 5 weight %, below the 2 weight %, below the 1 weight % or below the 0.5 weight %.
Film forming polymer
Film unit of the present invention comprises at least a water-soluble polymer.When needing, thin film also can comprise water-swellable polymer or insoluble polymer.
In some embodiments, the self-supporting heavy duty film comprises the water-soluble sugar based polyalcohol.For example, the glycosyl polymer can be cellulose or cellulose derivative.The object lesson of useful water-soluble sugar based polyalcohol includes but not limited to: dextrosan, amylopectin, hydroxypropyl emthylcellulose (HPMC), hydroxyethyl-cellulose (HPC), hydroxypropyl cellulose, carboxymethyl cellulose, sodium alginate, xanthan gum, Tragacanth, guar gum, acacin, arabic gum, starch, gelatin and their combination.
Some preferred embodiment in, the glycosyl polymer can be at least a cellulosic polymer, dextrosan or its combination.Thin film also can comprise the non-glycosyl polymer of water solublity or water-insoluble.The example of the non-glycosyl polymer of water solublity comprises: poly(ethylene oxide), polyvinylpyrrolidone, polyvinyl alcohol, Polyethylene Glycol, polyacrylic acid, methylmethacrylate copolymer, carboxy vinyl copolymer and their combination.The object lesson of useful insoluble polymer includes but not limited to: ethyl cellulose, Cellulose ethyl hydroxypropyl ether, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate and their combination.
Other preferred embodiment in, polymer is the combination of hydroxypropyl emthylcellulose and poly(ethylene oxide).Some other preferred embodiment in, polymer is the combination of dextrosan and poly(ethylene oxide).Other preferred embodiment in, polymer is the combination of dextrosan, hydroxypropyl emthylcellulose and poly(ethylene oxide).
Phrase used herein " water-soluble polymer " and variant thereof refer to be partially soluble at least water, preferably fully or most of water-soluble or absorb the polymer of moisture.In some embodiments, film unit of the present invention is exposed to wetting agent and dissolves up to small part., when being exposed to wetting agent, film unit of the present invention fully dissolves in other the embodiment at some.
The polymer that absorbs moisture is often referred to the water-swellable polymer.The used material of the present invention can have water solublity or water-swellable in room temperature and other temperature when being higher than room temperature.And described material can have water solublity or water-swellable under pressure below atmospheric pressure.Preferable, described water-soluble polymer is water solublity or the water absorption and swelling polymer with at least 20 weight % water intakes.Also can adopt the water-swellable polymer of water intake with 25 weight % or higher percentage ratio.Thin film of the present invention or the dosage form made by this class water-soluble polymer preferably have enough water solublity, can dissolve when contacting with body fluid.
Other polymer that can be used for mixing thin film of the present invention comprises biodegradable polymer, copolymer, block polymer and combination thereof.The known useful polymer or the type of polymer that satisfy above-mentioned standard are: poly-(glycolic) (PGA), poly-(lactic acid) (PLA), poly-diox, poly-oxalate, poly-(α-ester), polyanhydride, poly-acetas, polycaprolactone, poly-(ortho esters), polyamino acid, poly-amino-carbon acid esters, polyurethane, Merlon, polyamide, poly-(alkyl cyanoacrylate) and composition thereof and copolymer.Other useful polymer comprises, the space polymers of L-and D-lactic acid, the copolymer of two (right-the carboxyl phenoxy group) propanoic acid and decanedioic acid, the decanedioic acid copolymer, caprolactone copolymer, poly-(lactic acid)/poly-(glycolic)/ethylene glycol copolymer, the copolymer of polyurethane and (poly-(lactic acid)), the copolymer of polyurethane and poly-(lactic acid), the copolymer of a-amino acid, the copolymer of a-amino acid and caproic acid, the copolymer of α-benzyl glutamic acid and Polyethylene Glycol, the copolymer of succinate and poly-(ethylene glycol), polyphosphazene, poly-hydroxyl-alkanoate and composition thereof.Binary and ternary system have also been considered.
Other concrete available polymer comprises with trade name Medisorb and those commercially available polymer of Biodel.Described Medisorb material can be available from (the DupontCompany of E.I.Du Pont Company of Wilmington City, Delaware, USA State, Wilmington, Delaware), be designated as " poly (lactide-co-glycolide) " that contains " the 2-hydroxy polymer of propanoic acid, hydroxyl polymer-containing and hydroxyacetic acid " usually.4 kinds of these base polymers comprise lactide/glycolides 100L, it is believed that it is 100% lactide with the fusing point of 338-347 (170-175 ℃); Lactide/glycolides 100L it is believed that it is 100% Acetic acid, hydroxy-, bimol. cyclic ester with the fusing point of 437-455 (225-235 ℃); Lactide/glycolides 85/15 it is believed that it is 85% lactide and 15% Acetic acid, hydroxy-, bimol. cyclic ester with the fusing point of 338-347 (170-175 ℃); And lactide/glycolides 50/50, it is believed that it is to have 50% lactide of fusing point of 338-347 (170-175 ℃) and the copolymer of 50% Acetic acid, hydroxy-, bimol. cyclic ester.
Described Biodel material is represented the different polyanhydrides material of all kinds of chemical property.
Although can adopt various polymer, the polymer of selecting preferably provided the viscosity of expection for mixture before drying.For example, if local be insoluble to selected solvent, then need to provide to have more full-bodied polymer and help keep homogeneity with reagent or other component.On the other hand, if described component dissolves in solvent, then preferably provide to have more low viscous polymer.
Described polymer has played important function aspect the thin film viscosity influencing.Viscosity is the local a kind of characteristics of liquids with the stability of reagent in Emulsion, colloid or suspension of control.Usually the viscosity of substrate changes in 000 centipoise at about 400-100, preferably is about 800-60, and 000 centipoise is most preferably 1,000-40,000 centipoise.Preferably, become membrane matrix viscosity after the beginning dry run, can increase fast.
Can regulate described viscosity with component according to selected part, the part is selected according to intramatrical other component with component.For example,, then can select suitable viscosity, avoid influencing unfriendly the homogeneity of obtained thin film in case described component precipitates if described component is insoluble to selected solvent.Can regulate described viscosity with different modes.In order to increase the viscosity of film matrix, can select to have more high molecular weight polymers or can add cross-linking agent, as calcium salt, sodium salt and potassium salt.Can regulate viscosity by attemperation or by adding the tackify component.The component that can increase viscosity or stable emulsion/suspension comprises having more high molecular weight polymers, polysaccharide and colloid, includes but not limited to: alginate, carageen polysaccharide, hydroxypropyl emthylcellulose, locust bean gum, guar gum, xanthan gum, dextran, arabic gum, gellan gum and combination thereof.
Also observe, some polymer that needs plasticizer could obtain fexible film when using separately usually can combine, and also can obtain fexible film when not needing plasticizer.For example, when coupling HPMC and HPC, can obtain to have suitable plasticity and elasticity so that the flexible robust thin film of making and preserving.Its flexible acquisition does not need other plasticizer or polyhydric alcohol.
In addition, use separately or unite with hydrophilic cellulosic polymers and/or dextrosan and to use poly(ethylene oxide) (PEO) can obtain the thin film of flexible robust.No longer need to add plasticizer and obtain flexibility.Comprise HPC and HPMC with the non-limitative example of the suitable cellulosic polymer of PEO coupling.There are not gelation temperature basically in PEO and HPC, and the gelation temperature of HPMC is 58-64 ℃ (from the Methocel EF of DOW Chemical product company).And, even being substantially free of organic solvent, these thin film also have enough flexibilities, can remove organic solvent and do not damage property of thin film.Therefore, if there is no then there is not plasticizer in solvent in the thin film.Thin film based on PEO also has good tear resistance, has little or no curlingly, and when polymers compositions comprises the PEO of proper level, has quick rate of dissolution.
For realizing required property of thin film, the level of PEO and/or molecular weight can change in the polymers compositions.Changing PEO content can influence such as character such as tear resistance, rate of dissolution and adhesion tendentiousness.Therefore, a kind of method of controlling property of thin film is to change PEO content.For example, in some embodiments, need quick dissolving films.By changing the content of polymers compositions, can realize required dissolution characteristics.
According to the present invention, PEO preferably is about the 20-100 weight % of polymers compositions.In some embodiments, PEO content preferably is about the 1-200 milligram.Hydrophilic cellulosic polymers and/or dextrosan are about 0-80 weight %, or with the ratio of PEO up to about 4: 1, preferable ratio is about 1: 1.
In some embodiments, preferably change PEO content so that some property of thin film to be provided.For obtaining to have the thin film of high tear resistance and quick rate of dissolution, the preferred level of PEO in polymers compositions is about 50% or higher.For realizing antistick characteristic, prevent that promptly thin film from adhering to maxillary, the PEO level preferably is about 20%-75%.Yet, in some embodiments, may wish to realize the maxillary adhesiveness, when for example being animal or child's administration.In this case, can use the PEO of higher level.More particularly, the structural intergrity of may command thin film and dissolution make thin film adhere to mucosa and remove easily, perhaps adhere to more firmly and are difficult to remove, and specifically depend on specific application.
The molecular weight of PEO can change.May need high molecular PEO, for example about 4,000,000, improve the mucosa-adherent of thin film.More preferably, molecular weight is about 100,000-900,000, more preferably from about 100,000-600,000, most preferably from about 100,000-300,000.In some embodiments, may preferred combination high molecular (600,000-900,000) PEO and low-molecular-weight (100,000-300,000) PEO in the polymers compositions.
For example, some property of thin film, for example fast rate of dissolution and high tear resistance can be realized by a small amount of high molecular PEO and relatively large low-molecular-weight EPO are made up.Preferably, comprise about 60% or more high-load low-molecular-weight PEO in the PEO alloyed polymer component of this compositions.
Be balance antistick characteristic, quick rate of dissolution and good tear resistance, preferred film composite can comprise the low-molecular-weight PEO of about 50%-75%, randomly make up with a small amount of high molecular PEO, the remainder of polymers compositions comprises hydrophilic cellulosic polymers (HPC or HPMC) and/or dextrosan.
The controlled release thin film
Term " controlled release " refers to that the part discharges with the speed of reagent with chosen in advance or expection.For example, be in some embodiments of medicine in the part with reagent, preferably control the process that it discharges from thin film.This speed can change according to purposes.Preferred speed comprises fast or middling speed release profiles and delay, continue or discharge in succession.Also considered the combination of release mode, strengthened release during as beginning, then continued to discharge part reagent with reduced levels.Considered that also local pulsed with reagent discharges.
The polymer that is selected for thin film of the present invention can also make local with the controlled disintegrate of reagent.This can local realize that with the water-fast basically thin film of reagent described part discharges with certain speed with reagent by providing to contain in thin film.This can realize by mixing various solubility or insoluble polymer, can also contain biodegradable polymer in the combination.Perhaps, the controlled release part through coating can be mixed in the easy molten film matrix with the reagent granule, thereby realize local controlled release attribute with reagent.
Drug world recognizes for a long time, and giving can be more more convenient than giving repeatedly single dose with regular intervals with the single dose of drug of the long-time release of active ingredients of mode of control; Also recognize it concerning patient and clinician, have the levels of drugs that can make in the blood and continue the stable advantage of maintenance for a long time.
The part that the present invention adopts can be mixed in the film composite of the present invention of controlled release forms with reagent.For example, drug particles can be used polymer (as respectively with trade name such as Aquacoat ECD and commercially available ethyl cellulose or the polymethacrylates of Eudragit E-100) coating.Drug solution also can be adsorbed onto on the polymeric material and mix in the film composite of the present invention.Also can use other component in this controlled release composition.
Part reagent
When the part is imported thin film with reagent,, therefore can determine local amount described in the per unit area with reagent because thin film is equally distributed.For example, when thin film is cut into individual, can very accurately know the amount of the part usefulness reagent in the described dosage unit.This be because in the particular area local amount with reagent basically with another part thin film in the onesize area local amount with reagent identical.When described local be medicament when being medicine with reagent, accurate dose is especially favourable.
The active component that can mix thin film of the present invention includes but not limited to: medicine, cosmetics, beauty treatment medicine (cosmeceutical) and nutritional medicine (nutraceutical) activating agent.As used herein, the beauty treatment medicine is meant and comprises the cosmetics that user had the bioactive ingredients of effect.Nutritional medicine is meant usually to sell with the irrelevant medicine form of food and to have physiologic effect or have the product from food separation or purification of the protective effect of antagonism disease.The example of nutritional medicine comprises beta-carotene and lycopene.
As used herein, the part is meant the reagent that is applied to certain surface areas with reagent, such as but not limited to some skin area or mucosal tissue zone.Thin film can be used as delivery system, and the part is delivered to the certain surface areas that needs with reagent.
In some embodiments, thin polymer film preferably comprises at least a or multiple water-soluble polymer.In other the embodiment, thin film comprises the combination of water solublity and insoluble polymer at some.During moistening, the dry film product dissolves at least in part.Film product of the present invention is contacted with wetting agent allow local with reagent from Film Fractionation or dispersion.Wetting agent can be polar solvent, for example water.Dissolving or dispersive part can easily be applied to certain surface areas, for example skin area with reagent.
Wetting agent can be placed substrate surface, comprise skin and wound, then thin film be placed on the wetting surface.Perhaps, thin film is placed substrate surface, comprise skin and wound, carry out hydration then.
Wetting agent can disperse from container, and container can independence or is attached to thin film.For example, container can be pumping bottle or the sealed tube that comprises wetting agent.
Perhaps, container can be the sealing that the comprises wetting agent bag that can break.Bag can independence or is attached to thin film.When bag broke, wetting agent directly contacted with thin film, cause local with reagent from thin film stripping or dispersion, thereby the part is applied to substrate surface with reagent.
Thin film can be positioned between the container and substrate surface (comprising skin and wound) that comprises solvent.Perhaps, thin film can be between container that comprises solvent and applicator.
For example, in some embodiments, a kind ofly be used to apply local system and comprise with reagent: contain the soluble polymeric films of local usefulness reagent, may be present in the solvent in the container, and the applicator that is used for the part is applied to reagent substrate surface.In some embodiments, applicator is the sponge applicator.Thin film can be deposited on the sponge applicator top of moistening.Perhaps, thin film can be deposited on dry sponge applicator top, and then moistening.
As hereinafter further as described in, in some embodiments, a kind of method for preparing thin film of the present invention comprises: with water-soluble sugar based polyalcohol, polar solvent with locally make up with reagent, form and have non-self aggregation evenly heterogeneous wet material or substrate.In some embodiments, use the mixture of water-soluble polymer, for example at least a glycosyl polymer and poly(ethylene oxide).Then, wet material or substrate form thin film and dry in a controlled manner.In some embodiments, the part with polymer and polar solvent combination is the form of liquid, solid or gel with reagent.
When make up with water-soluble polymer in solvent with reagent the part, the type of material of formation depended on the dissolubility of local usefulness reagent and polymer.If reagent and/or polymer dissolve in the selected solvent, then form solution.But if each component is not dissolved, then the material of Xing Chenging is classified as Emulsion, colloid or suspensoid.
In some embodiments, local is personal care agents with reagent.Local also can be medicament with reagent.
The suitable part that can comprise in the thin film of the present invention includes but not limited to the example of reagent: soap, body detergent, shampoo, hair conditioner, hairspray, wetting agent, oxter deodorizer and/or Antiperspirant, emulsifiable paste or gel, sunscreen and anthelmintic shave.
Local also can be protein and/or peptide with reagent.For example, in some embodiments, local is collagen, elastin laminin or its combination with reagent.
Some preferred agents of topical application include but not limited to: the medicine and the anesthetis of acne medicine, antibacterial (as antibiotic), hormone, prevention motion sickness.
In some embodiments, medicament can be the nanoparticle size, for example less than about 500nm, mixes formation self-supporting heavy duty film of the present invention with water-soluble copolymer component.In other the embodiment, with the nanoparticle size, for example preferred medicament less than about 200nm mixes with water-soluble copolymer component, forms self-supporting heavy duty film of the present invention at some.
The active substance and the pharmaceutical composition that can contain various medicaments, biologically active in the dosage form of the present invention.The example of useful medicine comprises: the ACE-inhibitor, anti-anginal drug, anti-arrhythmic, antasthmatic, anti-cholesterol medicine, analgesic, anesthetis, anticonvulsant, antidepressants, antidiabetic drug, anti-diarrhoeic prod, antidote, hydryllin, antihypertensive, the antibiotic medicine, the antilipoid medicine, anti-manic medicine, antinanseant, Aggrenox, the antithyroid goods, antineoplastic agent, antiviral agent, the acne medicine, alkaloid, products of amino acid, cough medicine, antigout drug (anti-uricemic drug), antiviral agents, short anabolism goods, whole body and non-general anti-infective, anti-malignant-tumor agent, antiparkinsonism drug, antirheumatic, appetite stimulator, biological response modifier, Hemoregulatory, the bone metabolism regulator, cardiovascular drug, central nervous system's stimulant, cholinesterase inhibitor, contraceptive, decongestant, food additive, dopamine-receptor stimulant, intrauterine thin film dystopy controlling agent, enzyme, remedial agent for erectile dysfunction, fertility factor, gastrointestinal drug, homeopathic therapeutic method's agent, hormone, hypercalcemia and hypocalcemia controlling agent, immunomodulator, immunosuppressant, migraine agent, the motion sickness therapeutic agent, muscle relaxant, obesity control agent, the osteoporosis agent, oxytocic, parasympatholytic, parasympathomimetic agent, prostaglandin, psychotherapy's agent, breathe agent, analgesic, smoking deterent, sympatholytic, medicine trembles, the urinary tract medicine, vasodilator, laxative, antacid, ion exchange resin, antipyretic, appetite suppressant, expectorant, antianxiety drugs, antiulcerative, anti-inflammatory agent, coronary artery dilator, the brain expander, peripheral vasodilator, intend neurologic agent, analeptic, antihypertensive, vasoconstrictor, the migraine treatment agent, antibiotic, tranquilizer, psychosis, antineoplastic agent, anticoagulant, antithrombotic, sleeping pill, Bendectin, antinauseant, anticonvulsant, neuromuscular drug, blood glucose increasing and blood sugar lowering, thyroid and antithyroid drug, diuretic, spasmolytic, agent is speeded to delay in the uterus, antiadipositas drug, promoting erythrocyte generates medicine, antasthmatic, anti-tussive agents, mucolytic, DNA and genetic modification medicine and combination thereof.
Through considering that the example that can be used for active constituents of medicine of the present invention comprises antacid, H 2-antagonist and analgesic.For example, can singly prepare and separate acid supplement with the calcium carbonate composition or with magnesium hydroxide and/or aluminium hydroxide coupling.And, antacid can with H 2The coupling of-antagonist.
Analgesic comprises Opiate and opium derivant, as oxycodone (with
Figure A20068004551700341
Commercially available), ibuprofen, aspirin, acetaminophen and randomly contain the combination of caffeine.Other examples that are used for medicine of the present invention have opioid agonist and antagonist, as bupermorphine and Na Luo ketone.
Can be used for other preferred agents of the present invention as other preferred active component and comprise diarrhea medicine such as imodium AD, hydryllin, cough medicine, decongestant, vitamin and breath freshener.Chang Danyong or coupling be can contain in the film composite of the present invention and flu, pain, fever, cough, congestion, rhinorrhea or hypersensitive medicine treated, as acetaminophen, ibuprofen, chlorphenamine maleate, dextromethorphan, dextromethorphan hydrobromide, phenylephrine hydrochloride, pseudoephedrine hydrochloride, diphenhydramine and their combination, for example dextromethorphan hydrobromide or Arterenol (Hoechst). (with
Figure A20068004551700351
Commercially available).
This paper also consider to use antianxiety drugs such as alprazolam (with
Figure A20068004551700352
Commercially available); Psychosis such as Crow azoles flat (clozopin, with
Figure A20068004551700353
Commercially available) and haloperidol (with
Figure A20068004551700354
Commercially available); Non-steroid antiinflammatory drug (NSAID) as the bicyclo-chlorfenac (with Commercially available) and etodolac (with
Figure A20068004551700356
Commercially available); Hydryllin example hydrochloric acid diphenhydramine (with
Figure A20068004551700357
Sell), for example loratadine (with
Figure A20068004551700358
Sale), astemizole is (with Hismanal TMSell), nabumetone (with
Figure A20068004551700359
Disappear and sell), diphhydramine hydrochloride (with
Figure A200680045517003510
Sell) and clemastine (with
Figure A200680045517003511
Sell); Bendectin example hydrochloric acid granisetron (with
Figure A200680045517003512
Commercially available) and nabilone (with Cesamet TMCommercially available); Bronchodilator as
Figure A200680045517003513
Salbutamol sulfate (with
Figure A200680045517003514
Commercially available); Antidepressants example hydrochloric acid fluoxetine (with
Figure A200680045517003515
Commercially available), sertraline hydrochloride (with Commercially available) and paroxetine hydrochloride (with Commercially available); Anti-cough medicine is as guaifenesin; Antimigraine as
Figure A200680045517003518
ACE-inhibitor such as enalaprilat (with
Figure A200680045517003519
Commercially available), captopril (with
Figure A200680045517003520
Commercially available) and lisinopril (with
Figure A200680045517003521
Commercially available); Sick medicine of Kang Aercihaimoshi such as nicergoline; And Ca H-antagonist such as nifedipine (with With
Figure A200680045517003523
Commercially available) and verapamil hydrochloride (with
Figure A200680045517003524
Commercially available), tranquilizer/sleeping pill such as Zaleplon (with
Figure A200680045517003525
Sell) and dust assistant clone (eszopiclone, with
Figure A200680045517003526
Sell).
Remedial agent for erectile dysfunction includes but not limited to: can promote blood to flow to penis and influence the autonomic nerve activity, if can increase parasympathetic nervous (cholinergic) and the active medicine of minimizing sympathetic nerve (Adrenergic).Useful non-limiting medicine comprise 'Xiduofeng ' as
Figure A200680045517003527
Non-in it reaches (tadalafils) as
Figure A200680045517003528
Vardenafil, apomorphine as
Figure A200680045517003529
Yohimbine Hcl as
Figure A200680045517003530
With Alprostadil as
Figure A200680045517003531
Consider to be used for H commonly used of the present invention 2-antagonist comprises that cimetidine, ranitidine hydrochloride, famotidine, nizatidine, ebrotidine, mifentidine, roxatidine, a sand are for fourth and roxatidine.
Active antacid composition includes but not limited to following: aluminium hydroxide, dihydroxyaluminum aminoacetate, glycine, aluminum phosphate, mincid, bicarbonate, bismuth aluminate, waltherite, bismuth subcarbonate, bismuth subgallate, basic bismuth nitrate, basic bismuth salicylate, calcium carbonate, calcium phosphate, citrate ion (acid or salt), glycine, Magnesium sulfate heptahydrate aluminum, magaldrate, aluminium-magnesium silicate, magnesium carbonate, magnesium glycinate, magnesium hydroxide, magnesium oxide, magnesium trisilicate, milk solids (milk solid), one alkali formula or Bibasic Calcium Phosphate aluminum, tricalcium phosphate, potassium bicarbonate, sodium tartrate, sodium bicarbonate, aluminium-magnesium silicate, tartaric acid and salt.
The pharmaceutically active agents that the present invention adopts can comprise anaphylactogen or antigen, such as but not limited to: the plant pollen of grass, tree or artemisiifolia; The animal scurf is promptly from the skin of cat and other fur-bearing animal and the little squama of alopecia; Insecticide is as dermatophagoides pteronyssinus, Apis and wasp; And medicine, as penicillin.
Antioxidant can also be added thin film, to prevent especially heliosensitivity activating agent degraded of activating agent.
Coloring agent also can be used to prepare thin film.This based colorant comprises food, medicine and cosmetics coloring agent (FD﹠amp; C), medicine and cosmetics coloring agent (D﹠amp; Or topical drug and cosmetics coloring agent (Ext.D﹠amp C); C).These coloring agent are dyestuffs, their corresponding color lakes, and some natural and deutero-coloring agent.The color lake is the dyestuff that is absorbed on the aluminium hydroxide.
Other example of coloring agent comprises known azo dye, organic or inorganic pigment, or the coloring agent of natural origin.Preferred inorganic pigments, as ferrum or titanyl compound, in the gross weight of all components, the concentration of these oxides of adding is about 0.001-10%, preferably about 0.5-3%.
And, also can add aromatic in the thin film.They can comprise the extract that derives from plant, leaf, flower, fruit and combination thereof.
Other part reagent
Except personal care agents and medicament, term " the local reagent of using " can also be any reagent that is applied to certain surface areas.For example, local can be the cleaning agent that is applied to the substrate of needs cleaning with reagent.In one embodiment, local is kitchen detergent with reagent, can be attached in the thin film and drying.In case moistening, kitchen detergent disperse to come out, can be used for cleaning vessel or other surface from thin film.
Be used to send the thin film of emulsion composition
Some above-mentioned parts can be classified as emulsion composition with reagent.The fluid that Emulsion normally is made of the heterogeneous mixture of two kinds of general immiscible liquid phases, one of them liquid phase form the drop that suspends in another liquid phase.Emulsion composition includes but not limited to: the skin nursing emulsifiable paste, and sunscreen, anthelmintic, hair conditioner, hairspray (as, the hair thickening agent), some shampoo and drug ointment.These products are sold with liquid or semisolid (as, ointment) form traditionally.
Find that liquid/liquid Emulsion is captured in the flowable film matrix, Gu liquid/liquid Emulsion is converted into liquid/Emulsion when dry.Have at least portion of water to be evaporated in the captive Emulsion during the film drying.Gained dry film product can be the solid film substrate that wherein is dispersed with a plurality of discrete lipophilic drops, shown in drop form by liquid/liquid Emulsion deposition.Yet thin film is with after water contacts, and exsiccant thin film is rehydrated easily, with the dissolving water-soluble base and form Emulsion again.Term used herein " lipotropy " is meant that lipid is had affinity or captivation.
In some embodiments, the lipotropy drop that is captured on during the film drying in the thin film can comprise medicine.When water once more during the hydration dry film, form pharmaceutical emulsion, be applicable to topical application.
In some embodiments, the method for emulsion composition produced according to the present invention comprises: water-based emulsions is provided; Water-based emulsions is converted into non-water dry emulsion, shown in dry emulsion be the form of self-supporting heavy duty film.This method also comprises: use dissolution with solvents thin film forms water-based emulsions again.
Emulsion usually needs a large amount of kinetic energy with " emulsifying " each composition, as violent mixing or shearing, form oil droplet in aqueous medium, but product provided by the invention can pass through low-down energy input, and forms Emulsion at an easy rate after water contacts.Owing to be easy in water-soluble base, form and suspension lipotropy drop, in case substrate contacts the back dissolving with water, in the water around drop is easy to be suspended in.
The lipotropy drop preferably has the discrete individual droplets of microcosmic of affinity to lipid.For example, the lipotropy drop can be that fat drop, oil droplet, wax drip, sterol drips, glyceride oil droplet and their combination.
Thin film of the present invention can form by the compositions that preparation comprises following composition, and described compositions comprises at least a water-soluble polymer, polar solvent (as water) and emulsion composition.Then, from the composition forming film of preparation, described thin film drying and many lipotropy drops are dispersed in the thin film.Be applicable to film forming water-soluble polymer as mentioned above.The emulsion composition that is used to prepare thin film comprises activating agent, thereby during drying, many lipotropy drops that comprise activating agent are dispersed in the thin film.It is stable and complete that Emulsion during drying can keep effectively, and after adding water and making Film Fractionation, restructural forms Emulsion.But the Emulsion that forms of local application reconstruct then.
Thin film of the present invention is particularly useful for sending small drug granule, for example nano-particle.Nano-particle is interpreted as average-size usually less than 1 micron granule.This typically refers to average diameter.In some embodiments, Emulsion of the present invention comprises drug particles, nano-particle for example, and they are captured in the lipotropy drop, and the lipotropy drop itself is captured in the thin film, and with discharging after suitable solvent such as the aqueous medium reconstruct.Yet activating agent not only is present in the lipotropy drop, and is present in the thin film dielectrics.In addition, one or more different activating agents can be present in the lipotropy drop, and are present in the film matrix simultaneously.
In another aspect of this invention, can adopt liquid crystal structure to send and/or control the release of medicine, for example United States Patent (USP) 5,891, and 845 is described, and the content of this patent is introduced in this description in the reference mode.These liquid crystal structures can be included in the thin film.Liquid crystal structure comprises the solid solution of medicine and thin film.
Though do not wish to be subjected to the constraint of any theory, believe that in the present invention the thin film rheological equationm of state changes so soon between dry period, makes and usually disruptive Emulsion in fact still is kept perfectly when heating and water evaporates.Even all moisture are evaporated in the film drying process, the characteristic of Emulsion also can remain basically.When adding entry again in thin film, Emulsion forms again, can be used for local delivery or oral.
In some embodiments, dry run is included under the temperature that exceeds the emulsion composition phase transition temperature and heats thin film.The phase transition temperature of Emulsion is meant that Emulsion is converted into the temperature of oil in water emulsion from water in oil emulsion, and vice versa.Usually, if attempt to remove water by drying from water-based emulsions, then Emulsion will change a phase (being oil phase) into.But, the method according to this invention heating thin film, oil droplet take place coalescent before, oil droplet promptly is captured in the thin film, thereby makes this system keep stable being converted into than Emulsion under the high energy state of the phase time that do not have water.For example, in some embodiments, thin film is heated to temperature above the Emulsion phase transition temperature, so that many oil droplets are captured in the thin film.At some in other the embodiment, the about 10-15 of drying minute.
Among the present invention, Emulsion prepares by the following method: provide many lipotropy oil droplets to be scattered in wherein water-soluble polymer solid film; The thin film that is dissolved in water, thus Emulsion formed.Emulsion can be applicable to the surface of needs, for example body surface.
Another aspect of the present invention relates to the method for preparing the reconfigurable emulsion composition of water.This method comprises the preparation compositions, and it comprises at least a water-soluble polymer; Polar solvent; And emulsion composition.This method also comprises dry described compositions, comprises the dried breast of lipotropy drop with formation, and described drop is dispersed in the water-soluble polymer solid matrix.As mentioned above, dry run can be included under the temperature that exceeds the Emulsion critical transition temperature and heat.In some embodiments, form dried breast after dry about 10-15 minute.
In some embodiments, the system that is used to apply Emulsion comprises: do breast, this dried breast comprises the lipophilic liquid that is dispersed in the soluble polymeric films; And the solvent that is used to dissolve described thin polymer film.Solvent is provided, makes this solvent form dried breast, thereby the dried breast of reconstruct is applied to substrate surface, comprise skin and wound with doing newborn directly the contact with reconstruct.Solvent can be present in independence or be attached in the container of thin film.Suitable containers includes but not limited to: the broken bag of pumping bottle, sealed tube and sealing.
This system can randomly comprise applicator, is used for the Emulsion of reconstruct is applied to substrate surface.For example, applicator can be a sponge.In some embodiments, thin film deposition is at the sponge applicator top of moistening.At some in other the embodiment, thin film deposition is at the top of dry sponge applicator, and then uses wet with solvent, thereby applies the Emulsion of reconstruct.
Thin film can be between solvent-laden container and skin area.Perhaps, thin film can be between solvent-laden container and applicator such as sponge applicator.
In some embodiments, thin film of the present invention is applicable to delivering drugs, cosmetics, beauty treatment medicine or nutritional medicine activating agent.For example, can comprise above-mentioned any activating agent, for example medicine, vitamin, mineral, medicine, medical herbs, plant amedica, animal extracts or product, beauty treatment composition, beauty treatment medicine or nutritional medicine from the sedimentary lipotropy drop of liquid/liquid Emulsion.In some embodiments, in the activating agent dissolving lipotropy drop.In other the embodiment, activating agent is suspended in the lipotropy drop at some.
The thin film that is used for the eutectic compositions
The present invention also provides and has been applicable to the film composite of sending the eutectic composition dispersion.Film composite comprises: the water-soluble solid polymeric matrix; And many eutectic compositions drops that are dispersed in the substrate.Form the dispersion of eutectic compositions during film composite contact water.As described herein, the eutectic compositions is the mixture of fusing point than its two or more components that composition is low separately.
In some embodiments, eutectic compositions is the mixture of prilocaine and lignocaine.Find, can form the eutectic compositions by the hydrochlorate original position of lignocaine and prilocaine, shown in following examples.Particularly, in the available hydrogen sodium oxide original position and propitocaine hydrochloride, to obtain forming the required prilocaine substrate of eutectic compositions with lignocaine.In the presence of water, prilocaine/lignocaine eutectic mixture and polymer blend are merged the thin film that comprises the eutectic oil dispersion that formation can be examined under a microscope.In case moistening, Film Fractionation becomes opaque, shows that eutectic oil discharges with emulsion-type droplet form.
Dosage
The part that film product of the present invention can hold is very wide with the quantitative range of reagent.No matter required dosage is a height or extremely low, and thin film can both provide exact dose (size and the initial concentration of activating agent in polymer/water combination by thin film are determined).Therefore, according to the type of the part of mixing thin film with reagent or pharmaceutical composition, described local dosage with reagent can be up to about 300 milligrams, preferably up to about 150 milligrams or be low to moderate the microgram scope, or any amount between them.
Film product of the present invention and method are very suitable for medicine high-effect, low dosage.This is that height homogeneity by described thin film realizes.Therefore, preferably adopt low-dose drugs, especially have more the racemic mixture of the activating agent of usefulness.
Defoaming composition
Can also use the froth breaking component in the thin film of the present invention.These components help air, as air pocket, discharge described film-forming composition.As mentioned above, this air pocket may cause forming non-uniform film.A kind of defoamer that is particularly useful is a simethicone.Yet the present invention is not limited to this, can also use other defoamer.
Simethicone is generally used for medical field treatment baby's flatulence or stomachache.Simethicone is the linear siloxane polymers of exhaustive methylation and the mixture of silicon dioxide, and described polymer contains through the stable polydimethylsiloxane repetitive in trimethicone endcapped unit.It contains the polymethyl siloxane of 90.5-99% and the silicon dioxide of 4-7% usually.Described mixture is water-fast Lycoperdon polymorphum Vitt, translucent thick liquid.
When disperseing in water, simethicone can scatter at the water surface, forms the low surface tension thin film.Like this, simethicone can reduce the surface tension of foam gas (as foam bubble) in the solution, and they are broken.The effect of simethicone is similar to the dual function of water medium oil and alcohol.For example, because the density of oil-based liquid is littler than the density of aqueous solution, so any residual bubble in the oily solution all can rise to the surface and faster and more easily dissipation.On the other hand, known alcohol/aqueous mixtures can reduce the surface tension that water density can reduce water again.Therefore, any bubble that remains in the mixed solution also can dissipate at an easy rate.Simethicone solution has the advantage of above-mentioned two aspects concurrently.It can reduce the surface energy that remains in any bubble in the aqueous solution, also can reduce the surface tension of aqueous solution.Because have the function of this uniqueness, simethicone has fabulous defoaming, can be used for physiology method (anti-flatulence) and need remove in any externalist methodology of bubble in the product.
In order to prevent in thin film of the present invention, to form bubble, can under vacuum condition, carry out blend step.Yet in case described blend step is finished, and film solution gets back to normal atmosphere (An) condition following time, imports gas again or make it to contact with mixture.Under many situations, minute bubbles can residue in this polymeric adhesive solution once more.Simethicone is mixed the formation that bubble can be alleviated or eliminate to film-forming composition basically.
Simethicone can about 0.01-5.0 weight %, and the content of the better 0.05-2.5 of being about weight % and the most desirable 0.1-1.0 of being about weight % joins in the film forming mixture, as defoamer.
Optional components
Various other components and implant can also be added in the thin film of the present invention.These can include but not limited to: surfactant; Help to make the plasticizer of each component compatibility in the mixture; Polyhydric alcohol; Defoamer, as contain the chemical compound of silicone, it forms more level and smooth film surface by making thin film discharge oxygen; And thermosetting cement, as pectic substance, antler glue and gelatin, help to keep each component dispersibility.
The various additives that can mix the present composition can provide various function.The example of various additives comprises excipient, lubricant, buffer agent, stabilizing agent, foaming agent, pigment, coloring agent, filler, extender, spice, release regulator, adjuvant, plasticizer, incremental dose, releasing agent, polyhydric alcohol, granulating agent, diluent, binding agent, buffer, absorbent, fluidizer, binding agent, antitack agent, acidulant, softening agent, resin, demulcent, solvent, surfactant, emulsifying agent, elastomer and composition thereof.These additives can add with active component.
Useful additive comprises, for example gelatin; Vegetable protein is as the protein of Helianthi albumen, soybean protein, cottonseed protein, Semen arachidis hypogaeae protein, Semen Vitis viniferae albumen, lactalbumin, lactalbumin isolate, haemproteins, egg protein, acroleic acid esterification; Water soluble polysaccharide is as alginate, carageen polysaccharide, guar gum, agar-agar, xanthan gum, gellan gum (gellan gum), arabic gum and relevant glue (Ficus elastica, karaya, tragacanth), pectin; The plain derivant of water solublity derivative fibre: alkylcellulose, hydroxy alkyl cellulose and hydroxyalkyl alkylcelluloses, as methylcellulose, hydroxy methocel, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxyethylmethyl-cellulose, hydroxypropyl emthylcellulose, HBMC, cellulose esters and hydroxy alkyl cellulose ester such as cellulose acetate-phthalate (CAP), hydroxypropyl emthylcellulose (HPMC); Carboxyalkyl cellulose, carboxyalkyl alkylcellulose, carboxyalkyl cellulose ester such as carboxymethyl cellulose and their alkali metal salt; Water-soluble synthetic polymer such as polyacrylic acid and polyacrylate, polymethylacrylic acid and polymethacrylates, polyvinyl acetate, polyvinyl alcohol, polyvinyl acetate phthalate (PVAP), polyvinyl pyrrolidone (PVP), PVY/ vinyl acetate copolymer and poly-.beta.-methylacrylic acid; The water-soluble chemical derivant of the same gelatin that also has phthalate that is fit to, gelatin succinate, cross-linked gelatin, lac, starch, cation modified acrylate and methacrylate, it has for example tertiary amine groups or quaternary ammonium group, as diethyllaminoethyl, can ammoniumization when needing; And other similar polymer.
The optional addition of this class extender can be any amount, and preferable range is up to about 80 weight %, preferably is about 3-50 weight % and 3-20 weight % (based on the weight of all components) more preferably.
Other additive can be an inorganic filler, and as the oxide of magnesium, aluminum, silicon, titanium etc., its preferred concentration is about 0.02-3 weight %, preferably is about 0.02-1 weight % (weight of all components).
The example of other additive is a plasticizer, comprises to account for polymer weight 0.5-30%, and the concentration range that preferably is about 0.5-20% adds polyalkylene oxides, as Polyethylene Glycol, polypropylene glycol, polyethylene propylene glycol; The organic plasticizer of low-molecular-weight is as glycerol, glycerol Monoacetate, diacetin or triacetate; Vinegar essence, Polysorbate, spermol, propylene glycol, Sorbitol, diethyl sulfosuccinate sodium, triethyl citrate, tributyl citrate etc.
Can also add other chemical compound and improve the flowability of starch material, as preferred hydrogenated form, especially at room temperature be solid animal or plant fat.The desirable fusing point of these fat is 50 ℃ or higher.Preferred C 12-, C 14-, C 16-, C 18-, C 20-and C 22The triglyceride of-fatty acid.Can not add extender or plasticizer and add separately fat, and can be advantageously add separately or with monoglyceride and/or dibasic acid esters or phospholipid especially lecithin.Ideal monoglyceride and dibasic acid esters are derived from above-mentioned C 12-, C 14-, C 16-, C 18-, C 20-and C 22All kinds of fat of-fatty acid.
Total consumption of fat, monoglyceride, glycerol dibasic acid esters and/or lecithin accounts for the about 5% of total composition weight at most, preferably is about 0.5-2%.
Also be suitable for adding silicon dioxide, calcium silicates or the titanium dioxide that concentration accounts for the 0.02-1% of total composition weight.These chemical compounds play the effect of thickening agent.
The consumption of these additives is enough to realize intended purposes separately.Usually, the combination of some can change the whole release profiles of active component in these additives, can be used to regulate promptly hinder or quicken discharge.
Lecithin is a kind of surfactant of the present invention that can be used for.The feeding coal of lecithin can be about 0.25-2.00 weight %.Other surfactant, promptly surfactant includes but not limited to: spermol, sodium lauryl sulfate, ICI Americas Inc (ICI Americas, Inc) Spans of Chu Shouing TMAnd tween TMCan also adopt the oil of ethoxylation, comprise the Oleum Ricini of ethoxylation, sell as BASF AG
Figure A20068004551700421
EL.Carbowax TMBe the another kind of regulator very useful to the present invention.Can adopt tween TMOr the combination of surfactant realizes required hydrophilic-lipophilic balance (" HLB ").Yet the present invention can not need to adopt surfactant, and thin film of the present invention or one-tenth film composite can be substantially free of surfactant but still can provide uniform properties required for the present invention.
Can improve operation of the present invention and product if find other regulator, the applicant requires all other regulators of this class are included in the claim scope of the present invention.
Other composition comprises makes thin film be easy to be shaped and the common binding agent useful to the quality of thin film.The non-limitative example of binding agent comprises starch, pre-gelatinized starch, gelatin, polyvinyl pyrrolidone, methylcellulose, sodium carboxymethyl cellulose, ethyl cellulose, polyacrylamide, Ju Yi Xi oxazolidinone and polyvinyl alcohol.
Other potential additive comprises: solubilizing agent for example forms the material of inclusion compound with active component.These reagent help to improve the character of insoluble and/or unstable activating agent.Usually, these materials are ring molecules, have hydrophobic internal cavities and hydrophilic outside.Insoluble and/or unsettled activating agent can embed hydrophobic internal cavities, thereby forms inclusion complex, clathrate water soluble.Therefore, the formation of inclusion complex allow insoluble and and/or unsettled activating agent be dissolved in the water.The especially ideal example of this reagent comprises cyclodextrin, by the deutero-cyclic hydrocarbon of starch.Yet other similar material is also included within the scope of the present invention.
Form thin film
Thin film of the present invention must be in flakes before dry.After the required component formation of mixing comprises the multicomponent substrate of polymer, water and activating agent or other required component, as multicomponent substrate as described in pushing, be coated with, sprawl, cast or drawing, sheet or thin film are made in described combination by any known method in this area.Plural layers if desired can realize that described combination contains identical or different composition by more than one combination of coextrusion each component.Can also make plural layers by certain combination being coated with, sprawling or be cast on the thin layer that has been shaped.
Although can adopt various one-tenth thin film technique, preferably select a kind of method that can prepare fexible film, as the reverse roll coating process.The pliability of thin film make diaphragm can preserve or cut into various dosage forms before wind up and transport.Preferably, all right self-supporting of thin film, perhaps in other words, when not having independent holder, thin film can keep its integrity and structure.And thin film of the present invention can be selected from edible or digestible material.
The casting film compositions
The present invention adopts the preparation method of the equally distributed basically self-supporting heavy duty film of each component.This self-supporting heavy duty film is particularly useful for sending activating agent shown in this article.The method for preparing thin film is designed to keep the composition homogeneity of each component that distributes in the whole thin film, when the activating agent that is combined with in the thin film such as medicine, especially needs this homogeneity.For medicine, thin film must be formed evenly, so that can be divided into independently thin film dosage unit, when administration, each dosage unit has the activating agent of appropriate amount, thereby guarantees to obtain approved by management.
A kind of method for manufacturing thin film is referring to No. the 10/074th, 272, U.S. Patent application, its complete content in the reference mode in conjunction with in this manual.In the method, the film preparation process comprises: thin film is applied thermal air current in case the fluid stopping moving moves the formation that causes aggregation or aggregate with molecular separating force, thereby keep the composition uniform distribution of each component in the thin film, form the viscoelasticity thin film fast; Comprise that also dry viscoelasticity thin film is to form the self-supporting heavy duty film.
Preferably, the bottom surface of thin film is applied thermal air current, and end face there is not air-flow basically.This just makes that thin film is depth drying before top surface forms the polymer skinning, otherwise skinning will destroy film surface, cause heterogencity.Exsiccant self-supporting heavy duty film is being uniform aspect component distribution, weight and the thickness.
At first thin film is sent into surperficial top side, applied thermal air current then.The preferred activating agent that comprises therein take place before the degraded the time form the moistening thin film by degassing substrate in intersegmental.Then thermal air current is put on surperficial bottom side, and the essentially no air-flow in top side.This method also comprises the separate dosage units that exsiccant divided thin film is slit into same size and composition.Between dry period, the speed height of the thermal air current that the thermal air current that the thin film bottom surface applies applies than top surface.The thermal air current that applies for the dry film end face will be less than the degree that may cause the surface to form ripple or skinning.This just makes and thin film enough stiffs that becomes allow moisture to pass through non-skinning surfaces evaporation with locking volume homogeneity simultaneously on viscosity.
This method also comprises following preliminary step: the masterbatch pre-composition that forms edible water-soluble polymer and water; Make the pre-composition degassing by mixing; The degassing pre-composition of scheduled volume is sent at least one mixer; Active component is joined in the mixer; And mix each component to realize uniform distribution.Then, form moistening thin film and dry.
In order to form thin film of the present invention, coating or casting method are particularly useful, especially when the needs plural layers.Concrete example comprises reverse roll coating, intaglio plate coating, immerse or dip coated, measuring stick or Meyer (Meyer) rod is coated with, slit mould or extrusion coated, slit or knife-over-roll coating (gap or knife over roll coating), airblade coating, curtain coating or its combination.
When according to the present invention during film forming, adopt print roll coating or be particularly preferred more specifically for reverse roll is coated with.This method can control and make the thin film that obtains to have the desirable homogeneity of the present invention admirably.In this method,, described coating material is put on the application roll quantitatively by accurately being arranged on the slit between metering roll and its following application roll.During near described coating material being sent to application roll support roller, its can transfer to base material from application roll.Three rollers and four roller methods all are in daily use.
The intaglio plate coating process relies on the dandy roll that moves in the coating fluid to carry out, and rag point on the roller or the applied material of line are filled.Excessive coating material on the roller is wiped off with doctor blade, can be deposited on the base material in the time of then between coating material is by dandy roll and compression roll.
Photogravure is very common, and wherein coating material was deposited on the intermediate calender rolls earlier before transferring to base material.
Immerse or the simple procedure of dip coated in, base material immersed under the normal condition have in the low viscous coating fluid, so as described base material when exposing liquid level coating material can flow back in the impregnating bath.
In the metering roll coating process,, have excessive coating material and be deposited on the base material when base material during by the roller in the impregnating bath.Described wire-wound metering roll is sometimes referred to as Meyer rod (Meyer Bar), can stay the coating material of aequum on base material.Described amount is determined by the diameter of used line on the rod.
In the slit modeling method, by gravity or under pressure coating material is extruded slit, arrive on the base material.If coating material is 100% solid, this method just is called " squeezing and pressing method ", and in this case, linear velocity can be more much higher than extrusion speed usually.Can guarantee that like this coating layer is thin more a lot of than slot width.
In slit or the knife-over-roll method, coating material is put on the base material, then by " slit " between " scraper " and the support roller.After coating material and base material passed through, excess stock was scraped.
Airblade coating is that coating material is applied to base material, through the strong injection of air knife excess stock " is blown off ".This method can be used for the aqueous coating material.
In curtain formula coating process, the continuous coating material curtain that the bottom has the liquid pool generation of slit falls within two slits between conveyer belt.Object to be coated along conveyer belt with the controlled velocity process, thereby its upper surface can be received coating material.
The extrusion film compositions
In optional embodiment, form film product of the present invention by extruding rather than casting method.Extruding is particularly useful for comprising the film composite of poly(ethylene oxide) based polyalcohol component, and is as described below.For example, can adopt the single screw pressing method according to the present invention.According to this pressing method, in polymer melt, form pressure, make melt push or be injected in the mould by mould.
Especially preferred is to adopt pressing method to form the film composite that comprises the PEO polymers compositions.Comprise PEO or PEO blend in the polymers compositions of these compositionss, need not to add plasticizer and/or surfactant and polyhydric alcohol basically.
Under less than about 90 ℃ operative temperature, compositions is extruded with sheet-form.By the extrusion film compositions, make it carry out extrusion operation, to obtain even substrate by roller or mould.Then by the known any mechanism of those of ordinary skills cool off through the extruding film composite.For example, can adopt chill roll, air cooling bed or water cooling bed.Cooling step especially needs for the film composite that comprises the PEO polymers compositions, because PEO is easy to keep heat.When needing, form sheet material by said method and can form different shape.
Dry film
Drying steps also is a key factor of keeping described film composite homogeneity.When not having thickening composition or pass through the compositions of (for example) selective polymer control viscosity, the component in the thin film is easier to assemble or is coalescent, and select for use controlled drying means to be even more important this moment.Need not controlled drying steps to become the optional method of thin film with exact dose be at predetermined groove top casting thin film.When adopting this mode,,, can not make activating agent move to contiguous dosage form although therefore component can be assembled because each groove itself all defines dosage unit.
, can realize during controlled or quickly drying method when needs by the whole bag of tricks.The whole bag of tricks that can adopt comprises those methods of needs heating.Remove the liquid carrier in the thin film in a certain way, to keep the homogeneity that wet thin film has, the non-self aggregation of perhaps more specifically saying so is evenly heterogeneous.
Preferably, carry out drying from the thin film bottom to the thin film top.Preferably, during the primary solidification that forms the solid viscoelastic structure, the thin film top does not have the air communication mistake basically.This can occur in several leading second in, as about 0.5-4.0 minute of drying process.The dry top surface that can prevent that the conventional drying method from often causing of control is destroyed and the phenomenon that forms again in this way.Can be by forming thin film and placing the top side on surface to realize it with top side and bottom side.Then, earlier to the heating of thin film bottom surface, evaporation to be provided or to remove the necessary energy of liquid carrier.It is can be quickly dry to carry out exsiccant thin film in this way, even with the air drying thin film or compare also like this with the drying that the conventional drying means are carried out.Different with the edge with the at first dry top side of air drying thin film, the central authorities and the edge that carry out exsiccant thin film by heated base obtain drying simultaneously.Do like this and can also prevent with the normal composition deposited phenomenon that takes place of the exsiccant thin film of conventional means.
The film drying temperature is about 100 ℃ or lower, preferably is about 90 ℃ or lower, is most preferably 80 ℃ or lower.
In some embodiments, the weight of dry preceding polar solvent is at least about 30% of film weight.In some other embodiment, to thin film carry out drying the percetage by weight of polar solvent can be reduced to about 10% or below.Preferably, dryly in about 10 minutes or shorter time, take place.
Can use separately or comprise control with the method for the another kind of above-mentioned other control method coupling control drying process and regulate the interior humidity of the drying equipment that is used for dry film.In this way, can avoid top surface dry too early.
In addition, also find suitably to control the length of drying time, promptly thermal sensitivity and the volatility with some component especially flavored oils and medicine balances each other.Can make the length and the speed of energy, temperature and conveyer belt coordinate to adapt to this activating agent mutually, and drop to loss, degraded or the ineffectivity of final thin film minimum.
The object lesson of suitable drying means is disclosed by Magoon.Magoon has designed a kind of method that is exclusively used in dry pulp.Yet the inventor is used to prepare thin film with this technology.
The method and apparatus of Magoon all is based on the interesting characteristic of water.Although water can by portion within it and and the external world between conduction and convection current carry out energy delivery, water can only be in water and to the water Propagation of Energy.Therefore, the equipment of Magoon comprises and is used to place surface pulp, that can see through infrared radiation.Following and the temperature control pond on described surface contacts.The temperature in described pond preferably is controlled under the temperature a little less than the water boiling temperature.When the pulp that will wet places on this equipment surface, produce " refractance window ".This means that infrared energy sees through the surface and can only pass to by the occupied surf zone of pulp, and can only provide energy herein up to the pulp drying.The equipment of Magoon can provide thin film of the present invention at efficient drying in the time, reduced the clustering phenomena of film composition.
The another kind of method of control dry run relates to regional drying means.The zone drying equipment can comprise the driving-belt drying duct that wherein has one or more arid regions.The condition of each arid region can change, for example optionally assigned temperature and humidity.Preferably sorted successively in each zone, so that the acceleration drying effect to be provided.
The speed of the dry conveyer in zone is preferably successive.Perhaps, in the moment of dry run, speed can change, to increase or reduce the time that thin film exposes under the condition of desired zone.No matter continuously still through improving, regional drying can dry film and surface skining does not take place.
According to an embodiment of regional drying equipment 100, as shown in Figure 9, thin film 110 is sent into continuous conveyor 120, conveyer belt 120 delivery thin film are by each arid region.First arid region 101 that thin film passes through is warm moist zones.Second area 102 is hotter drier, and the 3rd zone 103 also is a heat and dry.These different zones can be successive, and perhaps they are independently, like that, have shown first arid region 201, second arid region 202 and the 3rd arid region 203 among the figure in the regional as shown in figure 10 drying equipment 200.According to the present invention, regional drying equipment is not limited to three arid regions.When needing, thin film can form the controlled drying effect of the present invention by more or less arid region with different temperatures and humidity level.
In order further to control temperature and humidity, the arid region also can comprise atmospheric condition, for example noble gas.The zone drying equipment can further be configured to comprise other process during regional dry run, for example spraying and lamination process need only and can keep controlled drying according to the present invention.
The original depth of thin film is about 500-1, and 500 microns, or about 20 mils-60 mil, dried thickness is about the 3-250 micron, or about 0.1-10 mil.In some embodiments, the thickness of film product is greater than 0.1 mil.In other the embodiment, the thickness of film product is about 10 mils or littler at some.In other embodiment, the thickness of film product is about the 0.5-5 mil.Preferably, the thickness of dry film is about the 2-8 mil, more preferably from about the 3-6 mil.
The test of thin film homogeneity
Preferably in the thin film fabrication process, test the chemistry and the physics homogeneity of thin film of the present invention.Specifically, the homogeneity of taking out film sample and testing each sample room film composition.Can check that also film thickness and overall appearance are with the test homogeneity.For the reason of safety and effectiveness, thin film is preferably uniformly, especially comprises the thin film of active constituents of medicine.
A kind of method of testing homogeneity according to the present invention comprises: transmit thin film in manufacture process.This process can comprise makes thin film experience dry run, divided thin film is slit into independently dosage unit, and/or packs this dosage unit etc.When transmitting thin film with conveyer belt equipment for example in manufacture process, it is become at least one part by transverse cuts.Described at least one part has the opposite end that is independent of any other film portion.For example, if thin film is a volume, it is cut into independently rouleau.The cutting thin film can realize by many methods, for example cutter, razor, laser or be used to cut any other suitable device of thin film.
Get the sample of some small pieces then respectively from the opposite end of each several part, but do not destroy the zone line of each several part as the cutting thin film.Keep the complete thin film of the overwhelming majority that allows of zone line not interrupt the thin film concordance by manufacture process and in thin film, form the gap of introducing sample.Therefore, when the thin film warp is further processed as packed, can alleviate losing the misgivings of dosage.And, the integrity of keeping cutting part or rouleau in whole process will help to reduce owing to dangerous control problem is interrupted the probability of further thin film being processed or packing, and described dangerous control problem is as because of finding that sample cuttings loses activating alarm and quit work.
After film portion is taken out terminal small pieces or sampling fragment, the homogeneity of each constituent content between working sample.Can adopt any conventional method of inspection or testing film sheet, for example, perusal, operational analysis equipment and any other suitable method well known by persons skilled in the art.If test result shows, there is heterogencity between film sample, then change manufacture process.This can save time and spend, because can change this process before finishing the whole manufacturing cycle.For example, can change drying condition, mixing condition, composition components and/or thin film viscosity.Change drying condition and comprise change temperature, drying time, humidity level and exsiccator location etc.
And, in whole manufacturing process, may need repeated sampling and testing procedure.Test the thin film dosage that to guarantee to produce continuously homogeneous at a plurality of intervals.Change to manufacture process can be implemented in any stage, to reduce the heterogencity of sample room as far as possible.
The application of thin film
Thin film of the present invention all is well suited for many application.The height homogeneity of film composition especially is fit in conjunction with medicament them.And, can select the polymer that is used to make up thin film, make the thin film disintegration time that a scope be arranged.The variation of thin film disintegration time or prolong can be used for realizing the control to the activating agent rate of release, thereby obtains to continue the delivery system that discharges.In addition, can activating agent be administered to skin or other body surface, comprise mucomembranous surface with thin film.
Thin film can be used for the topical administration activating agent.Can pass through the above-mentioned thin film of preparation, and they are introduced the mammal skin surface, wetting surface is finished then.When needing, can prepare thin film, and with its adhere to second or supporting layer on, use (promptly being applied to skin) before with described thin film from second or supporting layer peel off.Can thin film be adhered on any in preferred water-fast those supports known in the art or the back lining materials with binding agent.If the use binding agent, preferred use can not can change the binding agent of activating agent character.The mucoadhesive compositions also is useful.Described film composite itself is exactly mucoadhesive in many cases.
In case thin film of the present invention has utilized the thin film moistening rapidly-solublely to be inclined to.Can pass through thin film produced according to the present invention, it be introduced in the liquid making its dissolving, and activating agent is introduced liquid.This can be used for preparing the liquid dosage form of activating agent, topical application then.
Preferred specific film shape or size.Therefore, thin film can cut into any required shape or size.
Preferably, with blister-pack of the present invention in the secluding air and the packing of moisture of sealing, with the protection activating agent can oxidation, hydrolysis, volatilization and interact with environment.Figure 1 shows that packaged pharmaceutical dosage unit 10, as local application's agent.Dosage unit 10 comprises and is packaged in the bag separately or between paper tinsel and/or the thin film 12 of 14 of plastics lamination sheets.As shown in Figure 2, bag 10,10 ' can interconnect through peelable seam or porous seam 16.Bag 10,10 ' can be packaged into volume as shown in Figure 5 or piles up as shown in Figure 3, and sells with allotter form as shown in Figure 4.Described allotter can contain a whole set of medicine of usually leaving at the treatment of desiring to carry out, but thin thin film and packing make this allotter littler and more convenient than the conventional bottle that is used to place tablet, capsule and medicinal liquid.
Thin film of the present invention runs into wetting agent such as water, perhaps with after mucosal areas contacts dissolves immediately.Wetting agent makes the Topically active agent that comprises in the thin film from thin film stripping or dispersion.Then, the part easily can be applied to skin or other certain surface areas with reagent.
A series of such dosage units preferably are packaged into together according to scheme or the Therapeutic Method (as supply 10-90 days) that concrete therapy is advised.Each thin film can be packaged on the backing, tears off during use.
More fully embody the features and advantages of the present invention by following illustrative embodiment, and can not think restriction any way of the present invention.
Embodiment
Embodiment 1
The skin nursing emulsifiable paste is attached in the film matrix
The present invention relates to the skin nursing emulsifiable paste is attached in poly(ethylene oxide)/hydroxypropyl emthylcellulose (70/30) film matrix.The skin nursing emulsifiable paste that adopts in the present embodiment is an emulsion composition.Have been found that the gained thin film is suitable as soluble skin emulsion film (solids content 22.38 weight %).Composition is shown in Table A.
Table A
Component Weight (g)
Poly(ethylene oxide) WSR-N80 4.73
Hydroxypropyl emthylcellulose E15 2.03
The skin nursing emulsifiable paste 1 3.35
Sorbitan monooleate NF (sorbester p17) 2 0.04
1Available from Stockhausen company, comprise three kinds of compositions of 2.15g and 1.2g water.
2Available from Farma International company (Coral Gables, Florida).
Skin nursing emulsifiable paste and sorbitan monooleate and 29.85 gram distilled water combinations with Table A join in 1100 bowls of dish of Degussa (Degussa).Being mixed to join in bowl dish poly(ethylene oxide) and hydroxypropyl emthylcellulose (Table A) then.Adopt the multi-functional compression machine of Degussa dentistry (Degussa Dental MultivacCompact) to mix the mixture of each component.Specifically, the preparation process of solution comprises: under the vacuum that increases gradually, mix each component at interval with speed and the preset time of 125rpm, shown in table B.
Table B
Time (minute) Mixing velocity (rpm) Vacuum (Hg)
20 125 17
20 125 24
12 125 26.5
8 125 28
Employing have the micro-scalable wedge shape rolled piece that is set at 450 microns K-control coating machine (Griff, Fallsington, PA), on the HDP face of solution-cast to 6330,6330 coated face and 55#PS/1/5 " IN " release paper, casting film.In 80 ℃ of baking ovens,, be about 3.50% (HR73 moisture analyser) to humidity with film drying 15 minutes.Thin film is easy to peel off from whole base materials.
The gained film thickness is 2.8 mils, has good tear resistance, has enough intensity during tearing, inadhesion, and can be by 180 ° of crooked tests of moisture analyser.
One small pieces thin film with after the water-wet, is easy to dissolving in hands, be formed on the skin nursing emulsifiable paste of sprawling easily on the skin.Thin film with form Emulsion again after water contacts.
Present embodiment has proved the feasibility for preparing soluble skin emulsion film.Thin film is cut into 1 1/ 2Inch * 2 1/ 2The small pieces of inch, every heavy 148 milligrams, has the homogeneity of film composite.
Embodiment 2
Sunscreen is attached in the film matrix
The present invention relates to sunscreen is attached in poly(ethylene oxide)/hydroxypropyl emthylcellulose (70/30) film matrix.The sunscreen that adopts in the present embodiment is an emulsion composition.Have been found that the gained thin film is suitable as soluble sunscreen emulsion film (solids content 22 weight %).Thin film is formed shown in table C
Table C
Component Weight (g)
Poly(ethylene oxide) WSR-N80 4.90
Hydroxypropyl emthylcellulose 2.10
Sunscreen 3 1.92
Sorbitan monooleate NF (sorbester p17) 0.044
3Blue Eremiatis argi (Blue Lizard) is protected sunscreen, contains: 1.76 gram (20%) activating agent and other compositions; And 0.16 the gram water.
Sunscreen and the sorbitan monooleate and 31.04 of table among the C restrained distilled water and mix and join in 1100 bowls of dish of Degussa.Mixture with poly(ethylene oxide) and hydroxypropyl emthylcellulose joins in this bowl dish then.Adopt the multi-functional compression machine of Degussa dentistry (Degussa Dental Multivac Compact) under the described identical condition of the table B of embodiment 1, to mix the mixture of each component.
Employing has the K-control coating machine of the micro-scalable wedge shape rolled piece that is set at 450 microns, on the HDP face with solution-cast to 6330, and casting film.In 80 ℃ of baking ovens with film drying 15 minutes.Thin film humidity is 2.94% (HR73 moisture analyser).
The gained film thickness is 3 mils, and the surface has some speckles, curls, and has good tear resistance, and is 5 to the thin film adhesion rate of 6330 HDP face.Have enough intensity during tearing, inadhesion, and can be by 180 ° of crooked tests of moisture analyser.Thin film is cut into 1 1/ 2Inch * 2 1/ 2The small pieces of inch, every heavy 152 milligrams.
One small pieces thin film after the moistening, is easy to dissolving in hands, be formed on the sunscreen of sprawling easily on the skin.Specifically, form sunscreen Emulsion during the water dissolving films again.
Embodiment 3
Antibacterial soap is attached in the film matrix
The present invention relates to antibacterial soap (Equate board) is attached in poly(ethylene oxide)/hydroxypropyl emthylcellulose (70/30) film matrix, as soluble soap-film (solids content 22 weight %).Thin film is formed shown in table D.
Table D
Component Weight (g)
Poly(ethylene oxide) WSR-N80 5.21
Hydroxypropyl emthylcellulose E15 2.23
The liquid antibiotic soap 4 9.62
Sorbitan monooleate NF (sorbester p17) 0.044
4The Equate board comprises: 1.32 gram (15%) activating agent and other compositions; And 8.3 the gram water.
In 1100 bowls of dish of Degussa, antibacterial soap and sorbitan monooleate are mixed with 22.9 gram distilled water.Mixture with poly(ethylene oxide) and hydroxypropyl emthylcellulose joins in bowl dish then.Under condition shown in the table E, adopt the multi-functional compression machine of Degussa dentistry to mix the mixture of each component.
Table E
Time (minute) Mixing velocity (rpm) Vacuum (Hg)
20 100 17
20 100 19.75
12 100 22
8 100 25
Employing has the K-control coating machine of the micro-scalable wedge shape rolled piece that is set at 450 microns, with on the HDP face of solution-cast to 6330,6330 coated face and 55#PS/1/5 " IN " release paper (Griff), and casting film.In 80 ℃ of baking ovens,, be about 1.60% (HR 73 moisture analysers) to humidity with film drying 15 minutes.
The gained film thickness is about 4.5 mils, and the thin film adhesion rate of the HDP face to 6330 is 6, and gets loose on all base materials.Also have the tear resistance of appropriateness, have enough intensity during tearing, inadhesion, and can be by 180 ° of crooked tests of moisture analyser.1 1/ 2Inch * 2 1/ 2The diaphragm of inch weighs 150 milligrams.
One small pieces thin film dissolves fairly goodly in hands after the moistening, and makes soap produce foam on skin.
Embodiment 4
Shampoo is attached in the film matrix
Present embodiment relates to shampoo is attached in poly(ethylene oxide)/hydroxypropyl emthylcellulose (70/30) film matrix.Used shampoo is an emulsion composition in the present embodiment.Have been found that the gained thin film is suitable as soluble shampoo diaphragm (solids content 22 weight %).Thin film is formed shown in table F.
Table F
Component Weight (g)
Poly(ethylene oxide) WSR-N80 9.87
Hydroxypropyl emthylcellulose E15 2.08
Shampoo 5 7.70
Menthol 0.09
5Paris L'Oreal active nutritional moisturizing shampoo comprises 1.76 gram (solids content 20%) activating agent and other compositions; And 5.94 the gram water.
Menthol component and 25.26 gram distilled water are placed 1100 bowls of dish of Degussa.Then, the mixture with poly(ethylene oxide) and hydroxypropyl emthylcellulose joins in this bowl dish.Adopt the multi-functional compression device of Degussa dentistry shown in table G, to prepare solution.
Table G
Time (minute) Mixing velocity (rpm) Vacuum (Hg)
20 125 17
20 100 24
12 100 26.5
4 100 28
Shown in the table G between 4 minutes mixed zones after, shampoo is joined in the solution, the speed with 100rpm under vacuum (28Hg) continues to mix 4 minutes.Employing has on the HDP face of K-control coating machine with gained solution-cast to 6330 of the micro-scalable wedge shape rolled piece that is set in 450 microns, casting film.With thin film in 80 ℃ of baking ovens dry 15 minutes.Moisture is 2.82% (HR73=moisture analyser) in the thin film.
Film thickness is 3.4 mils, and the thin film adhesion rate of the HDP face to 6330 is 5.It also has the tear resistance of appropriateness, has good tear strength, inadhesion, and can be by 180 ° of crooked tests of moisture analyser.1 1/ 2Inch * 2 1/ 2The diaphragm of inch weighs 162 milligrams.In case moistening in hands, the dissolving of diaphragm is fairly good, and shampoo produces foam.Specifically, thin film forms Emulsion after with water dissolution again.
Embodiment 5A
The liquid kitchen detergent is attached to (solids content 25%) in the film matrix
In the present embodiment, the liquid kitchen detergent is attached in poly(ethylene oxide)/dextrosan (80/20) film matrix.Soluble detergent diaphragm comprises 25 weight % solids.Thin film is formed shown in table H.
Table H
Component Weight (g)
Poly(ethylene oxide) WSR-N80 6.4
Dextrosan 6 1.6
The liquid kitchen detergent 7 2.92
6Stay-Lite III board derives from Tate Lyle company.
7Dawn ultra concentration kitchen liquid detergent comprises: 2 gram activating agent and other compositions; And 0.92 the gram water.
The mixture and the 29.08 gram distilled water of poly(ethylene oxide) and dextrosan are joined in 1100 bowls of dish of Degussa.Adopt the multi-functional compression device of Degussa dentistry, as preparation solution as described in the Table I.
Table I
Time (minute) Mixing velocity (rpm) Vacuum (Hg)
20 125 17
20 125 24
12 125 26.5
4 125 28
After 4 minutes incorporation time sections shown in the Table I, liquid kitchen detergent component is joined in bowl dish, the speed with 125rpm under vacuum (28Hg) continues to mix 4 minutes.
Employing has the K-control coating machine of the micro-scalable wedge shape rolled piece that is set in 450 microns, on the HDP face and coated face with gained solution-cast to 6330.With thin film in 80 ℃ of baking ovens dry 15 minutes.The moisture of thin film is 3.85% (HR 73 moisture analysers).
Film thickness is 3 mils, and the thin film adhesion rate of the HDP face to 6330 is 4 and has a good tear resistance.It also has enough tear strength, inadhesion, and can be by 180 ° of crooked tests of moisture analyser.1 1/ 2Inch * 2 1/ 2The inch diaphragm weighs 168 milligrams.Diaphragm is soluble in water, forms suds.Yet soap concentration is not enough.Therefore, the suds that need higher concentration.Shown in embodiment 5B, in the film matrix that the soap adding of higher concentration is identical, find that it is suitable as soluble kitchen detergent thin film.
Embodiment 5B
Spissated liquid kitchen detergent is attached to (solids content 35%) in the film matrix
Present embodiment relates to spissated liquid kitchen detergent is attached in poly(ethylene oxide)/dextrosan (80/20) film matrix.Have been found that the gained thin film is suitable as soluble kitchen detergent thin film (solids content 35 weight %).Thin film is formed shown in table J.
Table J
Component Weight (g)
Poly(ethylene oxide) WSR-N80 7
Dextrosan 6 1.75
The liquid kitchen detergent 7 14.50
6Stay-Lite III board derives from Tate Lyle company.
7Dawn ultra concentration kitchen liquid detergent comprises: 8.75 gram activating agent and other compositions;
And 5.75 the gram water.
Distilled water (26.75 gram) is placed 1100 bowls of dish of Degussa.Mixture with poly(ethylene oxide) and dextrosan joins in bowl dish then.Adopt the multi-functional compression device of Degussa dentistry, shown in table K, prepare solution.
Table K
Time (minute) Mixing velocity (rpm) Vacuum (Hg)
12 125 17
12 100 24
8 100 26.5
4 100 28
After 4 minutes incorporation time sections shown in the table K, the liquid kitchen detergent is joined in bowl dish, the speed with 100rpm under vacuum 24Hg continues to mix 2 minutes.
Employing has the K-control coating machine of the micro-scalable wedge shape rolled piece that is set in 500 microns, on the HDP face with gained solution-cast to 6330, and casting film.With thin film in 80 ℃ of baking ovens dry 15 minutes.Moisture in the thin film is 4.78% (HR 73 moisture analysers).
Thin film is 9 to the thin film adhesion rate of 6330 HDP face, has good tear resistance, has enough tear strength, inadhesion, and can be by 180 ° of crooked tests of moisture analyser.4 inches * 2.75 inches diaphragms weigh 5.79 milligrams.Diaphragm is met water and is easily dissolved, and forms enough kitchen washing suds.
Embodiment 6
Other antibacterial soap is attached in the film matrix
Present embodiment relates to antibacterial soap is attached in poly(ethylene oxide)/hydroxypropyl emthylcellulose (70/30) film matrix.Thin film is suitable as the soluble soap-film of washing one's hands (solids content 22 weight %).Thin film is formed shown in table L.
Table L
Component Weight (g)
Poly(ethylene oxide) WSR-N80 4.87
Hydroxypropyl emthylcellulose E15 2.08
Antibacterial soap 8 2.86
Menthol .09
7The antibiotic hand soaps of Ultra Dawn comprises: 1.76 gram (20%) activating agent and other compositions; And 1.1 the gram water.
Menthol and 30.1 gram distilled water are placed 1100 bowls of dish of Degussa.Mixture with poly(ethylene oxide) and hydroxypropyl emthylcellulose joins in this bowl dish then.
Adopt the multi-functional compression device of Degussa dentistry, as preparation solution as described in the table M.
Table M
Time (minute) Mixing velocity (rpm) Vacuum (Hg)
20 125 17
20 100 24
12 100 26.5
4 100 28
After 4 minutes incorporation time sections in table M, add antibiotic hand soaps, the speed with 100rpm under vacuum 28Hg continues to mix 4 minutes.
Employing has the K-control coating machine of the micro-scalable wedge shape rolled piece that is set in 450 microns, on the coated face with the HDP face of gained solution-cast to 6330 and 6330, and casting film.With thin film in 80 ℃ of baking ovens dry 15 minutes.Percentage humidity is 2.6% (HR73 moisture analyser) in the thin film.
Film thickness is 3 mils, all gets loose from two kinds of base materials, and the thin film adhesion rate of the HDP face to 6330 is 5, and has appropriate tear resistance.It also has good tear strength, inadhesion, and can be by 180 ° of bend tests of moisture analyser.1 1/ 2Inch * 2 1/ 2The inch diaphragm weighs 153 milligrams.
After the hands moistening, the thin film caking shows the film matrix that the hand soaps needs are different.
Embodiment 7
Anesthetis is attached in the film matrix
Present embodiment relates to and prilocaine/lignocaine (50/50) eutectic is contained 50 milligrams dosage level with per 110 milligrams of diaphragms is attached in PEO/ hydroxypropyl emthylcellulose/dextrosan (70/10/20) film matrix.During film drying, the eutectic oil droplet is captured in the film matrix.In case the film matrix moistening is suitable as prilocaine/lignocaine eutectic dispersion.Prilocaine/lignocaine eutectic at room temperature is an oil, thereby has better percutaneous permeability than corresponding salt form.
Thin film is formed shown in table N:
Table N
Component Weight (g)
Poly(ethylene oxide) WSR-N80 5.82
Hydroxypropyl emthylcellulose E15 0.83
Dextrosan 1.66
Lignocaine/prilocaine (50/50) eutectic mixture 7.95
Sodium chloride 1.056
Menthol 0.17
In order to obtain to form the required prilocaine substrate of eutectic with lignocaine, to use among the NaOH and the hydrochlorate of prilocaine according to following reaction, this reaction original position is carried out, and is as further described below.
Prilocaine HCl+NaOH → prilocaine+NaCl+H 2O
Now the method for preparing film product will be described.At first distilled water (29.29 gram) is joined in 1100 bowls of dish of Degussa.Then 4.636 gram L-67s, 3.61 gram 20%NaOH solution (containing 0.722 gram NaOH and 2.88 gram water) and 3.977 gram lignocaine are joined in bowl dish with described order.Then, the blend with 0.17 gram menthol and poly(ethylene oxide), hydroxypropyl emthylcellulose and dextrosan joins in bowl dish.Adopt the multi-functional compression device of Degussa dentistry under the described condition of table O, to mix the mixture of each component.
Table O
Time (minute) Mixing velocity (rpm) Vacuum (Hg)
20 125 17
20 125 24
12 125 26.5
8 125 28
Employing has on the HDP face of K-control coating machine with gained solution-cast to 6330 of the micro-scalable wedge shape rolled piece that is set in 550 microns, casting film.Thin film was about 2.83% to humidity in dry 17 minutes in 80 ℃ baking oven.Thin film is cut into 1 1/ 4* 1 inch diaphragm weighs 107 milligrams.
Examine under a microscope, the gained thin film is the dry film that contains the eutectic oil dispersion.Thin film carries out above-mentioned observation after adding water, and is as further described below.
Dry film has excellent tear resistance, cohesiveness is only arranged slightly and have enough tear strength.It is 6 to the thin film adhesion rate of 6330 HDP face, is slit into gratifying size with die cuts.
Behind the skin moisturizing, thin film is placed on the wet skin, thin film begins fusion and becomes opaque, shows that eutectic oil discharges with the form of emulsion-type droplet.The oil passing in time that discharges is absorbed in the skin, and this can indicate by the reduction of thin film opacity.

Claims (136)

1. self-supporting heavy duty film, it comprises:
(i) comprise the water-soluble polymer composition of poly(ethylene oxide) and glycosyl polymer; With
(ii) part reagent.
2. thin film as claimed in claim 1 is characterized in that, described thin film is exposed to behind the wetting agent to the small part solubilized.
3. thin film as claimed in claim 1 is characterized in that, described thin film is exposed to behind the wetting agent solubilized basically.
4. thin film as claimed in claim 1 is characterized in that, described glycosyl polymer is selected from: at least a cellulosic polymer, dextrosan and combination thereof.
5. thin film as claimed in claim 1, it is characterized in that described glycosyl polymer is selected from: dextrosan, amylopectin, hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, carboxy methyl cellulose, sodium alginate, xanthan gum, Tragacanth, guar gum, acacin, arabic gum, starch, gelatin or its combination.
6. thin film as claimed in claim 1 is characterized in that described water-soluble polymer composition comprises the combination of hydroxypropyl emthylcellulose and poly(ethylene oxide).
7. thin film as claimed in claim 1 is characterized in that described water-soluble polymer composition comprises the combination of dextrosan and poly(ethylene oxide).
8. thin film as claimed in claim 1 is characterized in that described water-soluble polymer composition comprises the combination of dextrosan, hydroxypropyl emthylcellulose and poly(ethylene oxide).
9. thin film as claimed in claim 1, it is characterized in that described water-soluble polymer composition also comprises the non-glycosyl polymer that is selected from down group: polyvinylpyrrolidone, polyvinyl alcohol, Polyethylene Glycol, polyacrylic acid, methylmethacrylate copolymer, carboxy vinyl copolymer and combination thereof.
10. thin film as claimed in claim 1, it is characterized in that, described thin film also comprises insoluble polymer, is selected from: ethyl cellulose, Cellulose ethyl hydroxypropyl ether, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate or its combination.
11. thin film as claimed in claim 1 is characterized in that, described film thickness is greater than 0.1 mil.
12. thin film as claimed in claim 1 is characterized in that, described film thickness is that about 0.5 mil is to about 5 mils.
13. thin film as claimed in claim 1 is characterized in that, described part is a personal care agents with reagent.
14. thin film as claimed in claim 1 is characterized in that, described part is a medicament with reagent.
15. thin film as claimed in claim 1 is characterized in that, described part is a soap with reagent.
16. thin film as claimed in claim 1 is characterized in that, described part is the health washing reagent with reagent.
17. thin film as claimed in claim 1 is characterized in that, described part is a shampoo with reagent.
18. thin film as claimed in claim 1 is characterized in that, described part is a hair conditioner with reagent.
19. thin film as claimed in claim 1 is characterized in that, described part is a hair fixing reagent with reagent.
20. thin film as claimed in claim 1 is characterized in that, described part is a wetting agent with reagent.
21. thin film as claimed in claim 1 is characterized in that, described part is oxter deodorizer and/or Antiperspirant with reagent.
22. thin film as claimed in claim 1 is characterized in that, described part is shave emulsifiable paste or gel with reagent.
23. thin film as claimed in claim 1 is characterized in that, described part is a sunscreen with reagent.
24. thin film as claimed in claim 1 is characterized in that, described part is an anthelmintic with reagent.
25. thin film as claimed in claim 1 is characterized in that, described part is an antibacterial with reagent.
26. thin film as claimed in claim 25 is characterized in that, described antibacterial is an antibiotic.
27. thin film as claimed in claim 1 is characterized in that, described part is the acne medicine with reagent.
28. thin film as claimed in claim 1 is characterized in that, described part is a hormone with reagent.
29. thin film as claimed in claim 1 is characterized in that, described part is the reagent that prevents motion sickness with reagent.
30. thin film as claimed in claim 1 is characterized in that, described part is an anesthetis with reagent.
31. thin film as claimed in claim 30 is characterized in that, described anesthetis is the combination of prilocaine and lignocaine.
32. thin film as claimed in claim 1 is characterized in that, described part is protein or peptide with reagent.
33. thin film as claimed in claim 32 is characterized in that, described protein is selected from: collagen, elastin laminin and combination thereof.
34. thin film as claimed in claim 1 is characterized in that, described part is selected from reagent: medicine, cosmetics, beauty treatment medicine and nutritional medicine activating agent.
35. a soluble basically self-supporting heavy duty film, it comprises:
(i) water-soluble polymer composition, it comprises at least a glycosyl polymer; With
(ii) shampoo.
36. a soluble basically self-supporting heavy duty film, it comprises:
(i) water-soluble polymer composition, it comprises at least a glycosyl polymer; With
(ii) hair conditioner.
37. a soluble basically self-supporting heavy duty film, it comprises:
(i) water-soluble polymer composition, it comprises at least a glycosyl polymer; With
(ii) sunscreen.
38. a soluble basically self-supporting heavy duty film, it comprises:
(i) water-soluble polymer composition, it comprises at least a glycosyl polymer; With
(ii) antibiotic hand soaps.
39. a soluble basically self-supporting heavy duty film, it comprises:
(i) water-soluble polymer composition, it comprises at least a glycosyl polymer; With
(ii) kitchen detergent.
40. a soluble basically self-supporting heavy duty film, it comprises:
(i) water-soluble polymer composition, it comprises at least a glycosyl polymer; With
(ii) anthelmintic.
41. a soluble basically self-supporting heavy duty film, it comprises:
(i) water-soluble polymer composition, it comprises at least a glycosyl polymer; With
The emulsifiable paste of (ii) preserving moisture.
42. a soluble basically self-supporting heavy duty film, it comprises:
(i) water-soluble polymer composition, it comprises at least a glycosyl polymer; With
Emulsifiable paste or gel (ii) shave.
43. a soluble basically self-supporting heavy duty film, it comprises:
(i) water-soluble polymer composition, it comprises at least a glycosyl polymer; With
(ii) antibiotic.
44. send the part and use compositions and methods for one kind, described method comprises:
Dry film is provided, dissolving at least in part after this thin film moistening, described thin film comprises: (i) water-soluble polymer composition, it comprises poly(ethylene oxide) and glycosyl polymer; The (ii) local reagent of using;
Described thin film is contacted, the local reagent of using of stripping with wetting agent;
The part of stripping is applied to the surf zone that needs with reagent.
45. method as claimed in claim 44 is characterized in that, described wetting agent is a polar solvent.
46. method as claimed in claim 44 is characterized in that, described wetting agent is a water.
47. method as claimed in claim 44 is characterized in that, described wetting agent is from container allocation, described container independence or be attached to described thin film.
48. method as claimed in claim 44 is characterized in that, described part is applied to skin area with reagent.
49. method as claimed in claim 44 is characterized in that, described dry film is deposited on the skin moisturizing zone.
50. method as claimed in claim 44 is characterized in that, described dry film is deposited on the skin area, contacts with wetting agent then.
51. method as claimed in claim 44 is characterized in that, described part is applied to the substrate surface that needs cleaning with reagent.
52. method as claimed in claim 44 is characterized in that, described part is a personal care agents with reagent.
53. method as claimed in claim 44 is characterized in that, described part is a medicament with reagent.
54. method as claimed in claim 44, it is characterized in that described part is selected from reagent: sunscreen, wetting agent, shampoo, conditioner, hairspray, soap, anthelmintic, emulsifiable paste or gel, acne medicine, antibiotic, anesthetis, hormone or oxter product shave.
55. method as claimed in claim 44 is characterized in that, described glycosyl polymer is selected from: at least a cellulosic polymer, dextrosan and combination thereof.
56. method as claimed in claim 44, it is characterized in that described glycosyl polymer is selected from: dextrosan, amylopectin, hydroxypropyl emthylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, carboxy methyl cellulose, sodium alginate, xanthan gum, Tragacanth, guar gum, acacin, arabic gum, starch, gelatin or its combination.
57. method as claimed in claim 44 is characterized in that, described water-soluble polymer composition comprises the combination of hydroxypropyl emthylcellulose and poly(ethylene oxide).
58. method as claimed in claim 44 is characterized in that, described water-soluble polymer composition comprises the combination of dextrosan and poly(ethylene oxide).
59. method as claimed in claim 44 is characterized in that, described water-soluble polymer composition comprises the combination of dextrosan, hydroxypropyl emthylcellulose and PEO.
60. method as claimed in claim 44 is characterized in that, the thickness of described dry film is about the 0.5-5 mil.
61. a method for preparing the heavy film unit of self-supporting, described method comprises:
(a) with polar solvent, local with reagent and comprise poly(ethylene oxide) and the water-soluble polymer composition of at least a glycosyl polymer makes up, form the equally distributed material of described component;
(b) by described material filming;
(c) provide surface with top side and bottom side;
(d) thin film is sent into surperficial top side;
(e) heat with dry film in surperficial bottom side;
(f) the independently film unit that exsiccant divided thin film is slit into.
62. method as claimed in claim 61 is characterized in that, described combination step is included under the vacuum mixes each blending ingredients.
63. method as claimed in claim 61 is characterized in that, described material is by the reverse roll coating film forming.
64. method as claimed in claim 61 is characterized in that, described material is by the extruding film forming.
65. method as claimed in claim 61 is characterized in that, described drying is carried out under about 80 ℃ temperature.
66. method as claimed in claim 61 is characterized in that, described drying was carried out 10-15 minute approximately.
67. method as claimed in claim 61 is characterized in that, described drying is carried out in temperature control oven.
68. method as claimed in claim 61, described method also comprise each dry film unit is packed.
69. one kind comprises the allotter of film unit according to claim 1.
70. a compositions, it comprises:
The water-soluble polymer solid matrix;
Be dispersed in the many lipotropy drops in the described substrate;
Described compositions forms liquid/liquid Emulsion after being exposed to water.
71., it is characterized in that described polymeric matrix comprises the water-soluble polymer that is selected from down group as the described compositions of claim 70: biopolymer, through the biopolymer and the synthetic polymer of chemical modification.
72. as the described compositions of claim 70, it is characterized in that described polymeric matrix comprises the water-soluble polymer that is selected from down group: cellulosic polymer, poly(ethylene oxide), dextrosan, amylopectin, sodium alginate, xanthan gum, Tragacanth, guar gum, acacin, starch, gelatin, polyvinylpyrrolidone, polyvinyl alcohol, Polyethylene Glycol, polyacrylic acid, methylmethacrylate copolymer, carboxy vinyl copolymer or its combination.
73., it is characterized in that described lipotropy drop comprises activating agent as the described compositions of claim 70.
74. as the described compositions of claim 70, described compositions also comprises the activating agent that is dissolved in the lipotropy drop.
75. as the described compositions of claim 70, described compositions also comprises the activating agent that is suspended in the lipotropy drop.
76. as the described compositions of claim 70, described compositions also comprises the activating agent that is selected from down group: medicine, cosmetics, beauty treatment medicine and nutritional medicine activating agent.
77., it is characterized in that described lipotropy drop is formed by emulsion composition as the described compositions of claim 70.
78. a self-supporting heavy duty film that is used to send liquid/liquid Emulsion, it comprises:
The water-soluble polymer solid matrix wherein is dispersed with many discrete lipotropy drops that formed by emulsion composition.
79., it is characterized in that described polymeric matrix comprises the water-soluble polymer that is selected from down group as the described thin film of claim 78: biopolymer, through the biopolymer and the synthetic polymer of chemical modification.
80. as the described thin film of claim 78, it is characterized in that described polymeric matrix comprises the water-soluble polymer that is selected from down group: cellulosic polymer, poly(ethylene oxide), dextrosan, amylopectin, sodium alginate, xanthan gum, Tragacanth, guar gum, acacin, starch, gelatin, polyvinylpyrrolidone, polyvinyl alcohol, Polyethylene Glycol, polyacrylic acid, methylmethacrylate copolymer, carboxy vinyl copolymer or its combination.
81., it is characterized in that described lipotropy drop comprises activating agent as the described thin film of claim 78.
82., it is characterized in that described activating agent is selected from as the described thin film of claim 81: medicine, cosmetics, beauty treatment medicine and nutritional medicine activating agent.
83. a method for preparing Emulsion, described method comprises:
The water-soluble polymer that wherein is dispersed with many lipotropy drops solid film is provided;
The thin film that is dissolved in water, thus Emulsion formed.
84. as the described method of claim 83, it is characterized in that described water-soluble polymer comprises the water-soluble polymer that is selected from down group: cellulosic polymer, poly(ethylene oxide), dextrosan, amylopectin, sodium alginate, xanthan gum, Tragacanth, guar gum, acacin, starch, gelatin, polyvinylpyrrolidone, polyvinyl alcohol, Polyethylene Glycol, polyacrylic acid, methylmethacrylate copolymer, carboxy vinyl copolymer or its combination.
85., it is characterized in that described lipotropy drop comprises activating agent as the described method of claim 83.
86., it is characterized in that described activating agent is selected from as the described method of claim 85: medicine, cosmetics, beauty treatment medicine and nutritional medicine activating agent.
87. a method for preparing the thin film that is used for active agent delivery, described method comprises:
The preparation compositions, it comprises: at least a water-soluble polymer, polar solvent and comprise the emulsion composition of described activating agent;
Composition forming film by preparation;
By making many lipotropy drops that comprise activating agent be dispersed in method dry film in the thin film.
88. as the described method of claim 87, it is characterized in that described water-soluble polymer is selected from: cellulosic polymer, poly(ethylene oxide), dextrosan, amylopectin, sodium alginate, xanthan gum, Tragacanth, guar gum, acacin, starch, gelatin, polyvinylpyrrolidone, polyvinyl alcohol, Polyethylene Glycol, polyacrylic acid, methylmethacrylate copolymer, carboxy vinyl copolymer or its combination.
89., it is characterized in that described polar solvent is a water as the described method of claim 87.
90., it is characterized in that described emulsion composition is selected from as the described method of claim 87: shampoo, hair conditioner, hairspray, skin nursing emulsifiable paste, sunscreen, anthelmintic and cream.
91., it is characterized in that described activating agent is selected from as the described method of claim 87: medicine, cosmetics, beauty treatment medicine and nutritional medicine activating agent.
92., it is characterized in that described drying steps is included under the temperature above Emulsion critical phase transition temperature and heats as the described method of claim 87.
93., it is characterized in that the about 10-15 of described drying steps minute as the described method of claim 87.
94. a method for preparing the reconfigurable emulsion composition of water, described method comprises:
The preparation compositions, it comprises: at least a water-soluble polymer, polar solvent and emulsion composition;
Dry described compositions forms the lipotropy drop and is dispersed in the interior dry Emulsion of solid, water soluble polymeric matrix.
95. as the described method of claim 94, it is characterized in that described water-soluble polymer is selected from: cellulosic polymer, poly(ethylene oxide), dextrosan, amylopectin, sodium alginate, xanthan gum, Tragacanth, guar gum, acacin, starch, gelatin, polyvinylpyrrolidone, polyvinyl alcohol, Polyethylene Glycol, polyacrylic acid, methylmethacrylate copolymer, carboxy vinyl copolymer or its combination.
96., it is characterized in that described polar solvent is a water as the described method of claim 94.
97., it is characterized in that described emulsion composition is selected from as the described method of claim 94: shampoo, hair conditioner, hairspray, skin nursing emulsifiable paste, sunscreen, anthelmintic and cream.
98., it is characterized in that described lipotropy drop comprises activating agent as the described method of claim 94.
99., it is characterized in that described activating agent is selected from as the described method of claim 98: medicine, cosmetics, beauty treatment medicine and nutritional medicine activating agent.
100., it is characterized in that described drying steps is included under the temperature above Emulsion critical phase transition temperature and heats as the described method of claim 94.
101., it is characterized in that the about 10-15 of described drying steps minute as the described method of claim 94.
102. a method of sending emulsion composition, described method comprises:
Provide many lipotropy drops and be scattered in wherein water-soluble polymer solid matrix;
Make described polymeric matrix be exposed to wetting agent,, thereby form Emulsion with dissolve polymer substrate;
Described Emulsion is applied to the surf zone that needs.
103., it is characterized in that described Emulsion is selected from as the described method of claim 102: shampoo, hair conditioner, hairspray, skin nursing emulsifiable paste, sunscreen, anthelmintic and cream.
104., it is characterized in that described lipotropy drop comprises activating agent as the described method of claim 102.
105., it is characterized in that described activating agent is selected from as the described method of claim 104: medicine, cosmetics, beauty treatment medicine and nutritional medicine activating agent.
106. as the described method of claim 102, it is characterized in that described polymeric matrix comprises the water-soluble polymer that is selected from down group: cellulosic polymer, poly(ethylene oxide), dextrosan, amylopectin, sodium alginate, xanthan gum, Tragacanth, guar gum, acacin, starch, gelatin, polyvinylpyrrolidone, polyvinyl alcohol, Polyethylene Glycol, polyacrylic acid, methylmethacrylate copolymer, carboxy vinyl copolymer or its combination.
107., it is characterized in that described wetting agent is a water as the described method of claim 102.
108., it is characterized in that described wetting agent is from container allocation as the described method of claim 102, described container independence or be attached to described polymeric matrix.
109., it is characterized in that described lipotropy drop is formed by Emulsion as the described method of claim 102.
110., it is characterized in that described surf zone is a body surface area as the described method of claim 102.
111., it is characterized in that described polymeric matrix is deposited on the skin area of moistening and forms Emulsion as the described method of claim 102.
112., it is characterized in that described polymeric matrix is deposited on the skin area as the described method of claim 102, contact with wetting agent then and form Emulsion.
113. a compositions, it comprises:
The water-soluble polymer solid matrix;
Be dispersed in the many eutectic compositions drops in the described substrate;
Described compositions is exposed to the dispersion that forms the eutectic compositions behind the water.
114., it is characterized in that described eutectic compositions comprises the mixture of prilocaine and lignocaine as the described compositions of claim 113.
115., it is characterized in that described eutectic compositions is formed by the hydrochlorate original position of lignocaine and prilocaine as the described compositions of claim 113.
116. one kind is used to apply local system with reagent, described system comprises:
Be included in the part reagent in the soluble polymeric films, described thin polymer film comprises poly(ethylene oxide) and glycosyl polymer;
The solvent that is used for dissolving films, described solvent directly contact with thin film and make local with reagent from thin film stripping or dispersion, thereby the part is applied to the surf zone that needs with reagent.
117. as the described system of claim 116, described system also comprises the applicator that is used for described part is applied to reagent the surf zone of needs.
118., it is characterized in that described applicator is a sponge as the described system of claim 117.
119., it is characterized in that described thin film deposition is on the end face of the sponge applicator of using wet with solvent as the described system of claim 117.
120., it is characterized in that described thin film deposition applies part reagent then with wet with solvent as the described system of claim 117 on dry sponge applicator end face.
121., it is characterized in that described solvent is in container as the described system of claim 116.
122., it is characterized in that described container is independent of thin film as the described system of claim 121.
123., it is characterized in that described container is attached to thin film as the described system of claim 121.
124., it is characterized in that described thin film is between container that comprises solvent and skin area as the described system of claim 116.
125 as the described system of claim 117, it is characterized in that, described thin film is between container that comprises solvent and sponge applicator.
126. a system that is used to apply Emulsion, described system comprises:
Do breast, it comprises the lipotropy drop that is dispersed in the soluble polymeric films; With
The solvent that is used for dissolving films, described solvent rebuilds dried breast with doing breast directly to contact, thereby the Emulsion of reconstruct can be applied to the surf zone that needs.
127. as the described system of claim 126, described system also comprises the applicator that is used for the Emulsion of reconstruct is applied to the surf zone of needs.
128., it is characterized in that described applicator is a sponge as the described system of claim 127.
129., it is characterized in that described thin film deposition is on the end face of the sponge applicator of using wet with solvent as the described system of claim 127.
130., it is characterized in that described thin film deposition applies the Emulsion of reconstruct then again with wet with solvent as the described system of claim 127 on the end face of dry sponge applicator.
131., it is characterized in that described solvent is in container as the described system of claim 126.
132., it is characterized in that described container is independent of thin film as the described system of claim 131.
133., it is characterized in that described container is attached to thin film as the described system of claim 131.
134., it is characterized in that described thin film is between container that comprises solvent and skin area as the described system of claim 126.
135., it is characterized in that described thin film is between container that comprises solvent and sponge applicator as the described system of claim 127.
136. a method for preparing Emulsion, described method comprises:
(a) provide water-based emulsions;
(b) described water-based emulsions is converted into non-aqueous dried breast, wherein, described dried breast is the form of self-supporting heavy duty film;
(c) use dissolution with solvents thin film forms water-based emulsions again.
CN 200680045517 2005-12-06 2006-12-05 Topical film compositions for delivery of actives Pending CN101321511A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102869333A (en) * 2010-06-22 2013-01-09 雅芳产品公司 Magnetically-oriented cosmetic fibers
CN110494541A (en) * 2017-03-30 2019-11-22 陶氏环球技术有限责任公司 Self-supported membrane

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7357891B2 (en) 2001-10-12 2008-04-15 Monosol Rx, Llc Process for making an ingestible film
US20190328679A1 (en) 2001-10-12 2019-10-31 Aquestive Therapeutics, Inc. Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions
US20070281003A1 (en) 2001-10-12 2007-12-06 Fuisz Richard C Polymer-Based Films and Drug Delivery Systems Made Therefrom
US8765167B2 (en) 2001-10-12 2014-07-01 Monosol Rx, Llc Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions
US8603514B2 (en) 2002-04-11 2013-12-10 Monosol Rx, Llc Uniform films for rapid dissolve dosage form incorporating taste-masking compositions
US11207805B2 (en) 2001-10-12 2021-12-28 Aquestive Therapeutics, Inc. Process for manufacturing a resulting pharmaceutical film
US8900498B2 (en) 2001-10-12 2014-12-02 Monosol Rx, Llc Process for manufacturing a resulting multi-layer pharmaceutical film
US10285910B2 (en) 2001-10-12 2019-05-14 Aquestive Therapeutics, Inc. Sublingual and buccal film compositions
US8900497B2 (en) 2001-10-12 2014-12-02 Monosol Rx, Llc Process for making a film having a substantially uniform distribution of components
US20110033542A1 (en) 2009-08-07 2011-02-10 Monosol Rx, Llc Sublingual and buccal film compositions
CA2691272A1 (en) * 2007-06-29 2009-01-08 Union Carbide Chemicals & Plastics Technology Llc Hair styling and conditioning personal care films
US20100204341A1 (en) * 2007-06-29 2010-08-12 Wei Hong Yu Personal care dissolvable films
JP2010532377A (en) * 2007-06-29 2010-10-07 ユニオン カーバイド ケミカルズ アンド プラスティックス テクノロジー エルエルシー Personal care dissolvable film
US20090297591A1 (en) * 2008-05-30 2009-12-03 Orient Pharma Co., Ltd. Compositions And Methods For The Transdermal Delivery Of Pharmaceutical Compounds
KR102086311B1 (en) 2009-06-12 2020-03-06 선오비온 파마슈티컬스 인코포레이티드 Sublingual Apomorphine
EP2448553A2 (en) * 2009-06-30 2012-05-09 Dow Global Technologies LLC Sunscreen-containing dissolvable films comprising water-soluble cellulose ether
MY150626A (en) 2009-10-30 2014-02-07 Ix Biopharma Ltd Fast dissolving solid dosage form
ES2569339T3 (en) * 2010-06-10 2016-05-10 Midatech Ltd. Nanoparticle Film Management Systems
US9149959B2 (en) 2010-10-22 2015-10-06 Monosol Rx, Llc Manufacturing of small film strips
AU2011343429B2 (en) 2010-12-16 2016-10-20 Sunovion Pharmaceuticals Inc. Sublingual films
AU2012267605C1 (en) * 2011-06-10 2015-09-24 Aquestive Therapeutics, Inc. Combination peptide-nanoparticles and delivery systems incorporating same
JP2014214133A (en) * 2013-04-26 2014-11-17 日立化成株式会社 Method of producing nano film transfer sheet product, and transfer method of nano film layer of the nano film transfer sheet
FI127262B (en) 2013-09-04 2018-02-15 Yrkeshoegskolan Arcada Ab Microbiologically clean surfaces
JP6315754B2 (en) * 2013-10-02 2018-04-25 花王株式会社 Sheet cosmetic
WO2015107544A2 (en) * 2013-12-17 2015-07-23 Zim Laboratories Limited Pharmaceutical microemulsion immobilized in a thin polymer matrix and methods of making them
CA3127926A1 (en) 2015-04-21 2016-10-27 Sunovion Pharmaceuticals Inc. Methods of treating parkinson's disease by administration of apomorphine to an oral mucosa
US11273131B2 (en) 2016-05-05 2022-03-15 Aquestive Therapeutics, Inc. Pharmaceutical compositions with enhanced permeation
KR20190005199A (en) 2016-05-05 2019-01-15 어퀘스티브 테라퓨틱스, 아이엔씨. Enhanced delivery fffffrin composition
WO2019058397A1 (en) * 2017-09-21 2019-03-28 Jubeln Lifesciences, Pvt. Ltd. Formulation and development of topical or transdermal film
CA3105187A1 (en) 2018-06-28 2020-01-02 Arx, Llc Dispensing method for producing dissolvable unit dose film constructs
CN113149023B (en) * 2021-03-11 2023-05-02 昆明理工大学 Preparation method of mesoporous silica nanoparticle transdermal delivery eutectic system
CN116098882A (en) * 2023-04-06 2023-05-12 山东诚创蓝海医药科技有限公司 Composition containing lidocaine prilocaine and preparation method thereof

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19646392A1 (en) * 1996-11-11 1998-05-14 Lohmann Therapie Syst Lts Preparation for use in the oral cavity with a layer containing pressure-sensitive adhesive, pharmaceuticals or cosmetics for dosed delivery
DE10034491A1 (en) * 2000-07-15 2002-01-24 Scs Skin Care Systems Gmbh Foil dermatics
US20020131990A1 (en) * 2000-11-30 2002-09-19 Barkalow David G. Pullulan free edible film compositions and methods of making the same
US6419906B1 (en) * 2001-03-12 2002-07-16 Colgate Palmolive Company Strip for whitening tooth surfaces
JP4850346B2 (en) * 2001-03-15 2012-01-11 救急薬品工業株式会社 Mucosal patch
AU2002348432B2 (en) * 2001-10-12 2007-08-09 Aquestive Therapeutics, Inc. Thin film with non-self-aggregating uniform heterogeneity, process for their production and drug delivery systems made thereform
CA2411889A1 (en) * 2001-11-16 2003-05-16 National Starch And Chemical Investment Holding Corporation Films containing starch
JP2004043450A (en) * 2002-05-16 2004-02-12 Kyukyu Yakuhin Kogyo Kk Quickly soluble filmy preparation
US6841574B2 (en) * 2003-01-03 2005-01-11 Nexmed Holdings, Inc. Topical stabilized prostaglandin E compound dosage forms
WO2004087084A1 (en) * 2003-03-26 2004-10-14 The Procter & Gamble Company Rapidly dissolving edible film compositions with cellulose film forming polymers
FR2865130B1 (en) * 2004-01-21 2007-10-05 Oreal ANHYDROUS FILM FOR MAKE-UP OR CARE OF LIPS.
SE0401031D0 (en) * 2004-04-22 2004-04-22 Duocort Ab A new glucocorticoid replacement therapy

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102869333A (en) * 2010-06-22 2013-01-09 雅芳产品公司 Magnetically-oriented cosmetic fibers
CN110494541A (en) * 2017-03-30 2019-11-22 陶氏环球技术有限责任公司 Self-supported membrane
CN110494541B (en) * 2017-03-30 2021-04-30 陶氏环球技术有限责任公司 Self-supporting film

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JP2009518405A (en) 2009-05-07

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