United States Patent 3608070

The dressing excipient is composed essentially of vinyl pyrrolidone-vinylacetate copolymer which is soluble in a lower aqueous alcohol and which is capable of giving a film on the skin; a thixotropic agent of a triglyceride of hydroxylated fatty acids having 12-24 carbon atoms, preferably 12-hydroxystearic acid glyceride; a solvent for the resin, which fairly rapidly dries on the skin, namely aqueous alcohol; and a plasticizer of polyoxyethylene-glycol and/or acetoglycerides.

Application Number:
Publication Date:
Filing Date:
Primary Class:
Other Classes:
424/78.02, 602/52, 602/904
International Classes:
A61K8/02; A61K8/66; A61K9/70; A61L15/14; A61L15/42; A61L15/44; A61L26/00; (IPC1-7): A61B17/04; A61K15/00; A61L15/00
Field of Search:
128/156,334 424
View Patent Images:
US Patent References:
3214338Medicament releasing film-forming ointments and process of makingOctober 1965Ehrlich
2804073Fluid surgical dressingAugust 1957Gallienne et al.

Primary Examiner:
Rose, Shep K.
What is claimed is

1. An excipient for an adhering abrasion-resistant dry flexible surgical wound dressing applicable to an injured region of the skin for forming a solid nonocclusive film, covering the skin and permitting cutaneous breathing and perspiration thereof, upon drying, which consists essentially of, for each 100 parts of a copolymer of vinylpyrrolidone and vinylacetate, 15-35 parts of a thixotropic agent imparting rigidity, hardness and water resistance to the film, of a triglyceride of hydroxylated fatty acid of 12-24 carbon atoms, 20-40 parts of a plasticizer, preventing the film from pulling the skin, selected from the group consisting of the diacetic ester of glyceryl monooleate, polyoxyethylene glycol, and mixtures thereof, and 60-120 parts of an aqueous alcoholic solvent for the resin.

2. An excipient according to claim 1 wherein said thixotropic agent also comprises up to 80 percent thereof of a siliceous mineral material chosen from the group consisting of bentonite, colloidal silica and kaolin.

3. An excipient according to claim 1 wherein said thixotropic agent is the triglyceride of 12-hydroxystearic acid.

4. An excipient according to claim 1, characterized in that the plasticizer consists of the diacetic ester of glyceryl monooleate.

5. An excipient according to claim 1 wherein the solvent is aqueous ethanol.

The invention concerns a new surgical dressing applicable to the skin in the form of an ointment or cream which, on drying, leaves a solid, but flexible film.

It is often useful to be able to cover an injured region of the skin with an adhering film in order to maintain it in contact with a medicament substance, because it frequently occurs that known adhesive tapes must be avoided in certain patients because they produce manifestations of intolerance. On the other hand, on certain parts of the body, it is difficult or even impossible to apply an ordinary or adhering dressing. It is also known that difficulties are often encountered in removing a dressing from a painful part; even if there is no manifestation of particular intolerance, the removal may be very painful.

While adhering wound-dressing compositions embodying a water-soluble polymer have been contemplated, and some have even been commercialized, these prior compositions have not been entirely satisfactory and even those commercialized have not found wide usage. These prior compositions inevitably suffer from one or more of the following defects:

1. The drying time for the formation of the protective film is too long.

2. The film shrinks when drying.

3. The dried film peels off.

4. The dried film is not sufficiently flexible.

5. The dressing is difficult to remove with water.

6. The dressing is likely to stain garments when coloring substances, such as dyestuffs or tar, are present.

7. There is no sufficiently intimate adherence to dermatosis, and peripheral diffusion, causing secondary inflammation around the dermatosis, frequently occurs.

8. The dressing does not allow cutaneous perspiration to take place.

9. The dressing is too occlusive and does not let skin breath.

10. The medicament contained therewith too rapidly penetrates the patient's body.

The present invention solves these difficult problems and makes it possible to secure firmly over a small or large area of any part of the body a special dressing which can be readily positioned and removed. A considerable advantage of the new dressing resides in that it can be positioned in an extremely short time, for example of the order of 1 minute, and that is removed simply by dissolving it in water, accompanied by very light rubbing, so that the patient does not suffer any pain (on the other hand, the dressing will remain intact even when wetted as long as it is not rubbed). Another advantage of the new dressing according to the invention is the possibility which it offers for containing the desired medicament substances and the dressing permits only slow penetration of the medicament to the patient thus avoiding overall resorption. Thus, this new dressing can cover the skin and retain in position thereon an appropriate medicament, or even itself contain, in dispersion or solution, one or more suitable medicament substances. Other advantages include absence of staining, intimate adherence to dermatosis and the ability to permit both cutaneous perspiration and breathing of the covered skin.

The excipient of the new dressing may contain notably various active principles employed in dermatology, such as antibiotics and other bactericides, disinfectants, cicatrizants, cellular regeneration elements, antimycotics, anti-inflammatory agents, venotonic agents, anticoagulants, coagulants, analgesics, antiallergic diffusion products, keratolytics, revulsants, radio protectors, ichthammol, antisolar agents, antitussives, decontractants, local anaesthetics, sulphonamides, benzyl alcohol, quaternary ammonium compounds, zinc salts, enzymes, tars, coloring agents, and the like.

On the other hand, the excipient according to the invention is very suitable for the preparation of a paste based upon a radiological protector, for example Pb powder, Pb silicate or sulfate or the like.

It is known that such effective dermatological products as tars and various colored substances, for example parachlorophenoxetol, have unpleasant properties; these products stain everything and their stains are difficult to remove. Now, when they are incorporated in the excipient according to the invention, they remain just as effective, but completely cease to stain, since this excipient, which contains tar or coloring agent, forms on the skin a dry, completely nonsoiling film which can readily be removed with water. The application of the invention to this kind of medicament materials therefore affords a considerable advance.

The dressing excipient according to the invention is composed essentially of vinyl pyrrolidone-vinylacetate copolymer which is soluble in a lower aqueous alcohol and which is capable of giving a film on the skin; a thixotropic agent of a triglyceride of hydropylated fatty acids having 12-24 carbon atoms, preferably 12-hydroxystearic acid glyceride; a solvent for the resin, which fairly rapidly dries on the skin, namely aqueous alcohol; and a plasticizer preferably of polyoxyethylene-glycol and/or acetoglycerides.

The proportions of these constituents are such that the product obtained is in the form of an ointment or a cream, depending upon the concentration.

In addition to the essential triglyceride of hydroxylated fatty acid having 12-24 carbon atoms, such as the preferred 12-hydroxystearic acid glyceride or the alternate glycerides of acids such as ricinoleic, ricinostearolic, hydroxypalmitic, hydroxycapric or hydroxy arachidic, the thixotropic agent may also comprise other materials known to produce thixotropic effects, as referred to, for example, in Modern Plastics Encyclopedia, 1968, page 396. Such agents may be notable mineral, organic or mixed compounds, namely siliceous minerals, more particularly based on aluminum, magnesium and/or silicon and comprising hydroxy groups; kaolin; colloidal or microcrystalline silica; clays, above all of the montmorillonite group, notably bentonite, optionally modified by organic compounds such as amines or compounds having onium groups which replace some of the cations (Na) of the bentonite; oxides; carbonates or sulfates of alkaline-earth metals; metallic stearates, more particularly those of aluminum, zinc or calcium; waxes; etc; those preferred are cationic bentonite, kaolin and/or colloidal silic, particularly in extra fine form, e.g., aerosil. Where used, such other thixotropic agents may comprise up to 80 percent of the total thixotropic material present, the remainder being the triglyceride, preferably the triglyceride of 12-hydroxystearic acid.

The thixotropic agent performs a very special and important function in the dressing according to the invention, since it imparts to the product the mechanical stability necessary for obtaining an ointment. Without this constituent, the product would form a too-fluid mixture; owing to its presence, the ointment acquires, immediately after it has been spread onto the skin, appropriate rigidity and hardness, due to the thixotropic effect of the adjuvant. In addition, the thixotropic agent, more particularly triglyceride of hydroxystearic acid, imparts to the film obtained the desired resistance to water and to mechanical actions.

The proportion of thixotropic agent in the dressing composition may vary somewhat; generally, it is from 15 to 35 parts by weight based on 100 parts by weight of the resin, and preferably it comprises 18-27 parts by weight.

The plasticizer has the function of preventing the film from pulling the skin and flaking. As plasticizer there may be employed: (1) a polyoxyalkylene polyol (ether), such as polyoxyethylene glycol; (2) a mixed ester of polyol, i.e., a combination of a polyol (glycol, glycerine) with two different organic carboxylic acids, one of which is a fatty acid and the other a lower aliphatic acid; (3) a mixture of an ether (1) with an ester (2). The mixed esters can be illustrated by the following formulas in the cases of ethylene-glycol and of glycerine taken as polyols:

where R-CCOH is an aliphatic lower acid, such as for example acetic, propionic, butyric, etc., up to six carbon atoms, and R'-COOH is a fatty acid, for instance oleic, stearic, palmitic, etc.

Particularly useful seem acetoglycerides, that is mixed esters of glycerine as above, in which RCOO- is acetic group and R'COO- fatty acid moiety, mainly oleic. A particularly advantageous plasticizer is the diacetic ester of glyceryl monoleate. These materials function very well and are harmless to the skin. The proportion of plasticizer may be from 20 to 40 parts per 100 parts resin and preferably from 25 to 30 parts based on the weight of the resin.

The solvent most commonly employed in pharmacy being ethyl alcohol, it is ethanol (95°) [95 percent by volume] which constitutes the most suitable solvent for the excipient according to the invention. The total quantity of solvent is generally of the same order, i.e., about 60 to 120 parts per 100 parts resin, as that of the resin. However, the preferred quantity is 70-80 parts solvent per 100 parts resin.

The specific resin for use according to the invention is a copolymer of vinylpyrrolidone and vinyl acetate, containing by weight 20 to 80 percent of vinylpyrrolidone and 80 to 20 percent of vinylacetate. Best copolymers are those which contain 30 to 70 percent of vinylpyrrolidone with 70 to 30 percent vinylacetate. It has been found that particularly suitable excipient is obtained when one mixes a copolymer rich in vinylpyrrolidone (e.g., 60 to 70 percent vinylpyrrolidone) with a copolymer poor in vinylpyrrolidone (for instance having 30 to 40 percent of vinylpyrrolidone). Thus, a preferred dressing, according to the invention, contains a mixture of copolymers, such that in 100 parts of the mixture there are:

25 to 45 and better yet 28 to 38 parts of a copolymer having 60 to 70 percent vinylpyrrolidone, remainder vinylacetate and

75 to 55 and better yet 72 to 62 parts of a copolymer having 30 to 40 percent vinylpyrrolidone, remainder vinylacetate.

The new excipient is prepared by very intimately mixing the four kinds or more of the above-indicated compounds. It is to be noted that the finer the dispersion of the triglyceride of 12-hydroxystearic acid (with or without added bentonite) in the product formed, the more the latter imparts a favorable thixotropy to the formation of the dressing on the skin. As indicated above, various medicament substances may be incorporated in the excipient; this incorporation may take place during the preparation, or after the latter, by mixing the medicaments with the ointment already formed.

The invention is illustrated by the following nonlimiting examples:


Preparation of an excipient according to the invention. The weights are in grams.

Resin: vinyl polyvinylpyrrolidone acetate (PVP/AV) 630 [60% VP-40% V Acetate] 15 (PVP/AV) 335 [30% VP-70% V Acetate] 30 Thixotropic agents: triglyceride of 12-hydroxy-stearic acid ("Trixcin R") 4 aerosil 6 Plasticizers: polyoxyethylene glycol (Carbowax 400") 5 acetoglycerides LC (diacetic ester of glyceryl monooleate 7 Solvents: sterilized water 14.7 ethanol (95°) 2.4 egg yolk alcoholate (15%) 15.9

In the course of the manufacture, it is necessary to add a certain quantity of 95° ethyl alcohol in order to counteract the losses 1% the evaporation of the solvent. 2% 630 and the triglycerides of 12-hydroxystearic acid are first introduced. The two powders are first well mixed by stirring and the acetoglyceride LC and the egg yolk alcoholate are added. The mixture is stirred until a paste is obtained, whereafter the aerosil (colloidal silica) is added in proportions of 4 percent to 7 percent, and then the water. The mixture is stirred until all the lumps have disappeared. The polyoxyethylene glycol (Carbowax) is added and then the alcohol, if necessary, and finally the PVP/VA 335.

There is thus obtained a very unctuous ointment which can be readily applied to the skin. When used in a thin layer, it dries in less than a minute and gives a film having suitable resistance to abrasion, which is readily soluble in water, which facilitates washing, i.e., removal of the dressing.


Formula (a)

In 100 parts by weight of excipient prepared in accordance with example 1 is incorporated the following mixture:

0.4 part of Biclotymol, i.e., 2,2'-methylene-bis (4-chlorothymol)

0.2 part of parachlorphenoxytol

0.2 part of vitamin A acetate (100,000 IU/g)

0.6 g. of lignocain hydrochloride

6.0 parts of ethyl alcohol (95°)

0.12 part of 2.5 percent eosin solution.

Formula (b)

For an ointment for use by sportsmen.

Glycerol ether of ortho-cresol 10 g. Methyl nicotate 1 g. Escin (anti-inflammatory substance emanating from horsechestnut) 1 g. Glycol salicylate 5 g. Excipient q.s.%

Formula (c)

A product for application to the chest for coughing.

Isopropyl myristate 0.25 g. Methyl nicotate 0.25 g. Guaiacyl nicotate 0.50 g. Eucalyptole 3.0 g. Camphor 0.50 g. Pine oil 2.0 g. Thyme oil 1.0 g. Spirit of turpentine 2.0 g. Thymol essence 0.25 g.

Formula (d)

For blood circulation and massage of aching legs.

Escine 1.0 g. Lysozyme 1.0 g. Heparin 10,000 IU Hesperidin methyl chalcone 1% Nicotinic acid 2%


From 0.1 to 1 g. of hydrocortisone acetate is incorporated in the excipient of example 1, which gives an excellent anti-inflammatory dermatological dressing.


The following formulas, for 100 g. of excipient of example 1 illustrate some of the dressings comprising medicamental substances incorporated in accordance with the invention.

(Example 4) 0.10 to 1 g. of Biclotymol 0.10 to 1 g. of triamcinolone acetonide

(Example 5) 0.10 to 1 g. of neomycin sulfate (expressed as base)

(Example 6) 5 to 20 g. of undecylenic acid

(Example 7) 5 to 10 g. of flavonoids

(Example 8) 1 to 5 g. of promethazine


dihydroxyanthranol 0.2-10% Salicylic acid 1-20% or more (up to 500%) Resorcinol 1-20% Thioresorcinol 1-20% Coal tar 1-40% Vegetable tar 1-40% Thuya dye 1-20% Derivative of lead or other radio protector 1-100% Sulfur 5-30%

Other compositions according to the invention comprise the excipient, in which there has previously been dissolved or dispersed a dyestuff, for example methylene blue, acridine yellow, mercurochrome, silver fluoresceinate or the like. They may also serve as bases in antiacne masks. The excipient according to the invention is also suitable as a support for allergens.