Spray-spun bandage composition
United States Patent 1 Gurney SPRAY-SPUN BANDAGE COMPOSITION [75] Inventor: John A. Gurney, East Brunswick,  
 [73] Assignee: Johnson &amp; Johnson, New  
 Brunswick, NJ.  
 [22] Filed: Apr. 4, 1974 [21] Appl. No.: 457,875  
 [52] US. Cl. 128/155; 260/25 E [51] Int. Cl. A61f 13/00 [58] Field of Search 128/155-157,  
 [56] References Cited UNITED STATES PATENTS 3.419.506 12/1968 Gander 260/25 E 3,577,516 5/1971 Gould et a1. 128/155 3,608,070 9/1971 Nouvcl 128/156 3,705,669 12/1972 Cox et al. 260/25 E Primary E.\-aminer-Lawrence W. Trapp Attorney, Agent, or FirmSteven P. Berman; Jason Lipow [5 7 ABSTRACT A bandage composition especially suitable for application from aerosol containers onto wound surfaces. These compositions comprise A, B A, block polymers wherein the A, and A, blocks are a nonelastomeric polymers and the B block is an elastomeric polymer, together with solvents for the block polymers and propellants. The composition may also include local anesthetics and antibiotic or antiseptic agents. When applied to a wound surface, an opaque adherent flexible fibril mat, which is breathable to air, yet is largely occlusive to liquids is formed.  
 2 Claims, No Drawings SPRAY-SPUN BANDAGE COMPOSITHON- This application is a continuation-in-part of my copending applicationSer. No. 219,537, filed Jan. 20, 1972, now abandoned.  
 DISCLOSURE OF THE INVENTION The present invention relates to sprayable compositions that are useful for protecting such topical injuries as bruises, abrasions, minor cuts and burns, nonpoisonous insect bites and plant or contact dermatitis during the period of their healing. More particularly, this invention relates to compositions which are applied onto wound surfaces from aerosol containers.  
  The protection of wounds with various forms of adhesive cloth bandages is well known. Yet, despite the wide acceptance of such bandages, the advent of the formable so as not to hinder movement, and sufficiently comfortable so as not to motivate removal. Also, a bandage should wear well, and yet when desired be easily removed by peeling without injury to the healing wound.  
  Previous attempts to formulate sprayable bandage compositions for delivery from aerosol containers have not entirely met with success. Although they protect wounds satisfactorily, on the whole, they have not met the other requisites of a bandage such as wearability, air circulation and the like. Some commercial sprayable bandages have taken the form of films, but such films, following application, have had extended drying times and, therefore, were subject to dripping or sagging from the wound surface. Furthermore, such films were usually transparent and therefore required an opacifying agent, such as a starch derivative, in order to render the film opaque. From a patients psychological standpoint, a wound is preferably covered from view during its period of healing.  
  The compositions of this invention have the advantage that they spray not as wet material that dries forming a film, but rather they are spun in a semi-dry condition to form fibrils which mat, forming a fibrous covering for the wound.  
  The compositions of this invention can be applied at a minimal spin distance, that is, a minimal distance between the aerosol spray head and the wound surface which results in a less diffuse pattern and a concentration of the bandage where desired. After the mat is formed, there results a breathable-to-air dressing which is largely occlusive to liquids and maintains the wound surface in a&#39;clean condition. Furthermore, the dressings of this invention are adherent to the skin, providing for extended wear, and yet can easily be removed by peeling.  
  The composition &#39;of this invention comprises an A-B-A block copolymer wherein the A blocks are nonelastic polymers and the B block is an elastomeric polymer; these polymers being specifically chosen to provide the desirable properties enumerated above in a sprayable bandage composition. The chosen polymer is combined with a specifically chosen solvent. system and a propellant system to produce an aerosol delivered spray-on bandage will form the semi-dry fibrils as discussed above.  
  The block polymers that are suitable for this invention were selected from polymers described in US. Pat. No. 3,299,174 issued on Jan. 17, 1967 to Calvin J. Kuhre et a1. and US. Pat. No. 3,265,765 issued on Aug. 9, 1966 to Geoffrey Holden et a1. These polymers have the general formula:  
  A;B,,A where each A represents an independently selected nonelastomeric polymer block having a number average molecular weight in the range of 2,000 to 100,000 and a glass transition temperature above 33C each B represents an elastomeric polymer block having a number average molecular weight in the range of 25,000 to 1,000,000 and a glass transition temperature below 10C. Thus, x, y and z are large integers, such that A B and A would in of themselves be recognizable as high polymers.  
  These block copolymers are to be distinguished from graft polymers, wherein segments depend from intermediate points to a linear chain. One essential characteristic of the block copolymers used herein is that the elastomeric mid-section block has a glass transition temperature below 10C, preferably below 25C. Furthermore, while the end-section non-elastomeric blocks may have a molecular weight range from 2,000 to 100,000 and a glass transition temperature above 33C, it is preferable that the end-section blocks have number average molecular weights from 5,000 to 50,000 each and a glass transition temperature above 50C. Also, while the elastomeric mid-section block can have a number average molecular weight from 25,000 to 1,000,000 it is preferred that it be between 50,000 and 500,000.  
  The difference between the glass transition temperature of end-section blocks A and mid-section block B should suitably be at least 40C, preferably being to C. The end blocks in suitable polymers constitute l050%, preferably being 15-40% of the total polymer weight.  
  Specifically, in accordance with this invention, the A block, or inelastic portion of the copolymer is chosen to be polystyrene having an average molecular weight of from 2,000 to 100,000 and a glass transition temperature of at least 33C and constitutes about 10-50% of the total copolymer weight.  
  The B block, or elastomeric portion of the copolymer is selected from the group consisting of polyisoprene and polybutadiene and has a molecular weight of from 25,000 to 1,000,000 and a glass transition temperature of less than 10C.  
  The amount of copolymer which can be satisfactorily employed ranges from about 1.5 to 10% by weight of the total bandage composition. The use of a larger quantity of copolymer will usually result in the formation of a film, rather than the desired fibril strands. The use of less copolymer will require an extended spraying time to build up the desired mat, although after sufficient spraying with such a copolymer deficient composition, a satisfactory bandage will eventually form.  
  In this specific copolymer, the crystalline styrene domain crosslinks provide substantial tensile strength along with a low molecular weight which allows for an increased weight percent solubility. The isoprene or butadiene continuous phase of the copolymer contribute to the elasticity so apparent in these spray-spun ter of from about 7.3 to about 10. This latter term is defined in Polymer Handbook [V pp. 34l-368, Brandrup I et al. Editors, Interscience Publishers, N.Y., N.Y.,  
 (1967). The solvents from the extreme end of the soludressings. More particularly, the ratio of styrene to isobility parameter range tend to give a loss of either elasprene or butadiene and the molecular weight has been ticity or tensile strength, while solvents at the middle of found to affect properties of convenience such as the the range and blends of solvents having a solubility patime required to produce a dressing dry enough to use, rameter at the middle of the range are satisfactory. and an interrelated property of the distance between Some particularly desirable crosslinking regulators are the spray nozzle and the wound surface during applical0 petroleum ether, n-hexane, cyclopentane, cyclohextion. These properties are herein referred to as drying ane, n-heptane, n-octane, iso-octane, tetrahydrofuran, time and spin distance. The spin distance&#34; is the methyl ethyl ketone, ethyl acetate, methylene chloride minimum distance required to produce a fibril mat and acetone. The crosslinking regulator of choice is a which is free of visible bubbling or wetness and the mixture of acetone and cyclohexane, in a ratio no less drying time&#34; is the interval of time from the instant than 30% by weight acetone based on total weight of spraying has been completed until the mat can gently crosslinking regulator. Preferably the acetone is from be patted without deformation. 40-80% by weight. As already stated, the minimum Typical results for the preferred copolymers appear quantity of crystalline crosslinking regulator necessary below in Tables 1 and 2. In general, it appears that into achieve flexibility in the finished bandage and yet creases in molecular weight have an appreciable effect not unduly increase either spin distance or drying time on both spinning distance and drying time. should be employed. This quantity should comprise Table 1 from about 2-l0% by weight of the bandage composition based on the above suitable quantities of copolymer. T lDt&#39;ofA-B-ASt eBl kC lrne yplca a d 0c S152 rs Drying In Table 3 there 1s set forth the effect of the quant1ty Relalive of the crosslinking regulators on drying time and spin 17 v&#39; 11 s 1 met ,Z&#39;, wt 0 lscoslty Inc es S distance. Table 41llustrates the effect of the who of acetone to cyclohexane on spinning products. 1 Styrene l .230 3 4 lsoprene 70 Table 3 2 Styrene 15 1.432 4 5 30 lsoprene 85 3 Styrene 28 1.293 4 6 Effect of Solvent on Spin Distance and Drying Times Butadiene 72 Upright Inverted 4 Styrene 40 L435 5 l0 Solvent, g Spin Dry Spin Dry Butadiene 60 3.0 12:0.4 3.2:11 3.1102 3311.3 An index of molecular weight. Determined at 30&#34;C and 0.4 wtfl in toluene. 6.0 3310.7 4.0:tl .4 3.2+0.6 3.0+l .2 65 of copolymer. 5 g tetrahydrol&#39;uran, 196g 65/35 and 60/40 9.0 3.6.10.9 4.01512 3,410.9 3.8il.6 dichlorndilluoromethane-vinyl chloride blends.  
  *7.0:0.9g of copolymer 1. l80g 52/48 wt.&#39;71 vinyl chloride dichlorodifluoromethane, lOg dimethyl ether. solvent /60 wt T bl 2 acetone-cyclohexane.  
 . 40 Molecular Weight Comparison of Spinning Factors Tabl 4 Can Upright Can Inverted Copolymer, 6g Mats/can Spin Dry Spin Dry Cyclohexane and Acetone l&#34; 26il 4:1 7i Sfl Sfl By Weight of Acetone in Upright Inverted 2+ 2115 10:3 15:4 14:3 18:4 Cyclohexane/Acetone Mixtures Spin Dry Spin Dry &#39;10; 40/60 actone-cyclohexane, 190g 38/62 vinyl chloride/CF, 61, I00 4 2 6 5 +10g 40/60 acetone-cyclohexane, 190g 35/65 vinyl chlorideICF Cl1 8O 4 4 l0 5 60 8:2 812 1634 7 0 6i3 6:3 14+ 11 In order for the polymer to form the deslred fibrils as it leaves the aerosol spray-head, it must be contained &#34;with a gcopolymer 1; 78.4 g vinyl chloride; ll7.6 gdichlorodillurormethane. in the aerosol can in a dissolved state. This is accom- I plished by dissolving the copolymer in a solvent system To provide the drlvmg force for expuls1on of the comprising an appropriate propellant blend nd ancompos1t1on from the aerosol contamer, apropellant 1s other solvent referred to herein as a crystalline crossused- In Order to provide for a conslstent composmon linking regulator, i.e., regulating the amount of endthroughout the period of use, as prevlously stated, 1t 15 section block crystalline cross-linking domains during des1rable that the propellant, and the balance of the use. Preferably the solvent system forms a stable single compositlon form a smgle llquid phase. wrth th1s criteliquid phase, but solvent systems that are meta-stable, ia in ind, any Suitable propellant recognized by the forming a single liquid phase upon agitation of the aeraerosol art 1s suitable provided that 1t 1s 1nert chemlosol container are also satisfactory. It is desirable that cally to the balance of the spray spun bandage compothe minimum amount of crosslinking regulator solvent sition. Suitable and usually employed propellants 1nbe employed so as to promote rapid drying of the mat. clude vinyl chloride and mixtures of vinyl chloride and As a crystalline crosslinking regulator for the polymers, dichlorodifluoromethane. In addition, other propelgenerally solvents such as cyclic and straight and lants such as other fluorochlorohydrocarbons known as branched chain hydrocarbons of C to C in length; the the Freons and the Genetrons can also be employed as lower alkyl carboxylic acid esters, the di-substituted lower alkyl carbonyls; and the mono and di halogen substituted lower alkyl groups have a solubility paramepropellants. The preferred propellant is a blend of dichlorodifluoromethane and vinyl chloride in a range of 40 to 50% by weight propellant of dichlorodifluoromethane and 60 to 50% by weight propellant of vinyl chloride. Blends of propellants having 60% or more dichlorodifluoromethane by weight form two liquid phases, the upper phase containing copolymer 1 (Kraton XT-610l) and a lower phase containing only propellants, and the cyclohexane and acetone blend. Meta-stable solution blends of 65% by weight dichlorodifluoromethane and 35% by weight vinyl chloride can be prepared by dissolving the copolymer first in the vinyl chloride and then adding the dichlorodifluoromethane. These 65/35 blends reverted to a system of two liquid phases after two to three months storage and are not considered as satisfactory as the other specified propellants and propellant blends.  
  The quantity of propellant used is critical only in that if an insufficient. amount is used the driving force to expel the entire composition from the container will be lacking. Generally, the composition comprises from 75-95% by weight propellant. Propellant in excess of this amount is wasteful and requires a prolonged spraying to form a suitable bandage. Using less does not utilize fully the contents and results in inconveniently long spinning distances of the aerosol container, although some suitable bandages will initially be formed until there no longer is sufficient propellant to expel the contents of the container.  
  In order to improve on the quality of the fibrils formed, it has been found desirable to replace a portion of .the usually employed propellant or propellant blend in the formulation with a different propellant herein termed a fibril regulator. This fibril regulator has a lower boiling point than the usually employed propellant and is capable of developing higher pressures. Such fibril regulators should independently develop a pressure of at least 70 lbs/in gauge at 20C. Preferred fibril regulators include propane, dimethylether, monochloropentafluoroethane (F-1l5), and chlorodifluoromethane (F-22). They preferably replace no more than about of the usually employed propellant, i.e., no more than about 9.5% by weight of the spray spun bandage composition. Additional fibril regulator does produce finer fibrils but can develop pressures which are excessive for the integrity of the aerosol container under conditions of high temperature, such as can be encountered under storage conditions.  
  These components, the block polymers, the propellants and the solvent, are those that are essential to a spray-spun bandage formulation. In addition, the formulation, if desired, can also include small but effective amounts of anesthetics, antibiotics and antiseptics.  
  Examples of antiseptics or anti-infectives which can be included in the spray-spun bandage formulation are the quaternary ammonium salts such as alkyldimethylbenzyammonium chloride commercially available as Zephiran Chloride; ethylmercurithio salicylic acid (commercially available as Thimei&#39;osal); and benzyl phydroxybenzoate (Benzyl paraben). These are included at concentrations of about 0.5 to 0.01% by weight and like the antibiotics are preferably dissolved in the solvent or propellant to insure uniform application.  
  Where an antibiotic is employed, it is preferable that it be dissolved in either the solvent or propellant as opposed to being dispersed, although this is satisfactory. The antibiotics are used at concentration of less than 1% of the total formulation weight and generally are effective at a concentration of&#39; 0.050.01%= The 91% ferred antibiotics are bacitracin and neomycin although depending on the bacterial strains expected to be encountered, erythromycin, the penicillins and tetracyclines, as well, can be employed.  
  It is sometimes desirable that a local anesthetic be included in the formulation even though the cooling effect of evaporating propellant does provide some anesthesia.  
  The preferred anesthetics are those of the same type especially benzocaine, ethyla&#39;minobenzoate and butylaminobenzoate, which are used in concentrations of from about 0.5 to 0.01% by weight.  
  To further illustrate the spray spun bandage compositions of this invention, the following examples are set forth for the purpose of elucidation and not limitation.  
 EXAMPLE I A spray-spun bandage formulation was prepared by dissolving 6.0g of a block copolymer comprising 30% styrene and isoprene which had a relative viscosity of 1.230 in 100g of a cosolvent composed of 40% by weight acetone and 60% by weight cyclohexane. This solution was loaded into a conventional aerosol container fitted to receive a valve with a 0.020 inch inside diameter vapor tap and having a 0.040 inch inside diameter body and capillary dip tube with l90.0g of a blend comprising 38% by weight vinyl chloride and 62% by weight CF C1 The valve was immediately crimped to the cooled can which completed the filling operation. When the contents of this can were applied to a model wound, the formulation had a spin distance of 4:1 inches. The drying time was 7:3 seconds. When the container was sprayed in the inverted position, the spin distance was 5:2 inches and at this spin distance had a drying time of 8:3 seconds.  
  The bandage formed had good wear qualities and could be peeled off without difficulty. There were 26:1 mats of an approximate 2 inch diameter delivered from the can that wore well up to 8 hours.  
 EXAMPLE ll Another spray-spun bandage formulation was prepared by dissolving 6.0g of a block copolymer comprising 15% styrene and isoprene which had a relative viscosity of 1.432 in 10.0g of a solvent as in Example 1. This solution was then cold loaded into a conventional aerosol container with l90.0g of a mixture comprising 35% by weight vinyl chloride and 65% by weight dichlorodifluoromethane. When sprayed on a model wound surface the upright can delivered 21&#39;5 mats that were easily removed by peeling or rubbing. These mats had a spin distance of 10:3 inches and a drying time of 15:4 seconds. When the container was sprayed in the inverted position the spin distance was l4fl inches and the drying time 18:4 seconds.  
 EXAMPLES 111 V1 Formulations were prepared as in Example 1 except in place of the block copolymer there used, 6.0g of.  
 each of the block copolymer referred to in Table 1.  
 EXAMPLE V11 T0 the solutiil 6f copolymer and solvent of Exaifi&#39;ple l is added 01055 @f bacitracin and 0.05g of nearnyaia.  
 EXAMPLE V111 A 48/52 wt blend of dichlorodifluoriilthane vinyl chloride condensed to liquid with a dry iceisopropanol cold bath was added to a seamless steel aerosol can which contained 7g of copolymer l and 3g of 40/60 wt acetonecyclohexane. Immediately after the blend was weighed in, g of dimethyl ether also liquidied with a dry ice bath was added and a valve with a 0.020 in. vapor tap and 0.050 in. capillary dip tube crimped into place.  
 Can pressure at 70F 60&#39; *l psig Mats/can 46:2  
 Spin distance, upright 3.4i0.6 in Spin distance, inverted 3110.2 in Drying time, upright 3.4il.2 sec Drying time, inverted 2.7:] 0 sec To determine the effects of the spray-spun bandage on wound healing, the spray-spun bandage of Example Vlll was tested on a linear incisional wound model as follows:  
  The upper backs of four human volunteers were clipped and then prepped with PREPTIC SWAB. Three, superficial incisions MM long and approximately 300p. deep were made with a sterile scalpel (blade No. ll). The incisions were then sprayed with the spun dressing for 12-15 seconds at a distance of 4-5 inches. The central portions of the wounds were biopsied once to yield information at l, 2 and 3 days post wounding. The biopsies were small, elliptical samples obtained after infiltration of these areas with ca. 0.3-0.4cc 2% lidocaine hydrochloride. The fresh tissue was quick-frozen for cryotomy (Slee HR Cryostat). Sections were cut at 6 1., fixed in Wolmans solution and stained with hematoxylin and eosin.  
  Gross observations of the incisions revealed a slight to moderate eschar formation on day 1 post wounding. The eschar was present on all wounds for the three days post wounding. Inflammation was slight to moderate on all wounds on day 1 post wounding. By day 3 post wounding, only one wound was slightly inflamed. No gross infection was seen in any of the wounds at any of the time periods.  
  After seven hours of wear only two of the four subjects had the dressing intact over the wounds. The edges of the dressing were not adhered. The intact dressings were resprayed as were the exposed wounds. On day 1 post wounding, only one original dressing was intact. All wounds were resprayed. On day 2 post wounding, one subject had one dressing from day 0 intact. Two subjects had one dressing intact each while the fourth subject had both dressings intact. Once again, all areas were resprayed. By day 3 post wounding, all the dressings were intact.  
  Three of four wounds were re-epithelialized on day 1 following wounding. The wounds were slightly hyperplastic and a fibrin network was seen in the dermis. Slight inflammation was evidenced by the presence of a few polymorphonuclear leukocytes. An eschar was seen in all of the wounds.  
  By day 2 post wounding, all wounds were reepithelialized and slightly depressed. Once again an eschar was seen in all of the wounds. By day 3 post wounding, the epidermis was differentiated as evidenced by the presence of the granular layer. A slight scab remained on the wounds.  
  Histological evaluation of human incisions dressed with Spun Dressing showed that three of four wounds were re-epithelialized by day 1 post wounding. All wounds were re-epithelialized by day 2 and differentiated by day 3 post wounding. No gross inflammation was seen in these wounds at any of the time periods tested. No dressing particles were seen in the wounds.  
  These results indicate that the Spun dressed wounds healed better than previously studied untreated wounds.  
 WHAT IS CLAIMED IS:  
  1. A bandage composition for dispensing a fibrous covering for a wound from aerosol containers comprismg:  
 about 1.5 to 10% by weight of the bandage compositionof an A-B-A block copolymer wherein (1) said A block is polystyrene having an average molecular weight of from 2,000 to 100,000 and a glass transition temperature of at least 33C and constituting about lO-50% of the total copolymer weight and (2) said B block is selected from the group consisting of polyisoprene and polybutadiene, said B block having a molecular weight of from 25,000 to 1,000,000 and a glass transition temperature of less than 10C;  
 about 2-l0% by weight of said bandage composition comprising a mixture of acetone and cyclohexane, said mixture comprising no less than 30% by weight of said acetone; and a propellant comprising -95% by weight of the bandage composition, a portion of said propellant comprising no more than 10% by weight of said bandage composition being capable of independently developing a pressure of at least 70 pounds per square inch guage at 20C, said propellant and said acetone-cyclohexane mixture having together a solubility parameter of from about 7.3 to about 10.  
 2. The composition of claim 1 wherein said acetone in said mixture comprises 40 to by weight.