FR2718330A1 - Antiseptic articles. - Google Patents

Abstract

Sanitary or hygienic antiseptic articles, in particular for packaging pharmaceuticals, foodstuffs and cosmetics, and at least partially consisting of a non-occlusive assembly of filaments made of synthetic material, particularly nitrocellulose, polyamide, especially polyhexamethylene adipamide, and epsilon-caprolactam polymer, and surface-saturated with benzalkonium chloride of which at least 50 % consists of a tetradecyl radical incapable of being released under the expected conditions of use.

Description

ANTISEPTIDE ARTICLES
The invention relates to the plastics industry and their applications in the fields of pharmaceutical, cosmetic, food packaging and sanitary or hygiene articles. It is more particularly articles made of filamentary plastic material with antiseptic properties.

 The properties of certain plastics are known for superficially fixing antiseptic substances. This is particularly the case of polyamides with benzalkonium chloride. But it has been found that the retention capacity and, consequently, the antiseptic efficiency of the treated polyamides varied according to the types of polyamide and benzalkonium chloride and their degree of saturation. This variability of the properties is incompatible with the marketing of industrial products of quality and constant properties.

où R désigne un radical alkyle de structure CnH2n+l où n est un nombre pair compris entre 8 et 18, les valeurs n = 12 et 14 étant prédominantes. The most widely used commercial benzalkonium chloride as antiseptic, especially in eye drops, is a mixture of alkylbenzyldimethylammonium chlorides of the general formula

where R denotes an alkyl radical of structure CnH2n + 1 where n is an even number between 8 and 18, the values n = 12 and 14 being predominant.

The C12 compound is generally present at 40% in the mixture and that at C14 at 20%. The C12 + set
C14 constituting at least 70% of the mixture.

 However, comparative studies have revealed that it is the compound with n = 14 (tetradecyl radical C14H29) which has the best antiseptic activity.

Bactericidal activity of BAK

<tb> Length <SEP> of <SEP> Concentration <SEP> minimal <SEP> bactericidal <SEP> in <SEP> lml <SEP>
<tb><SEP> channe <SEP> R <SEP> S. <SEP> Aurens <SE> S. <SEP> Typhosa <SEP> Aeruginosa
<tb><SEP> C12 <SEP> 45 <SEP> 40 <SEP> 120
<tb><SEP> C14 <SEP> 15 <SEP> 12 <SEP> 40
<Tb>
Other comparative studies have revealed that among the synthetic materials commercially suitable for superficially fixing benzalkonium chloride, the most effective chemically and mechanically are nitrocellulose, polyhexamethylene adipamide, sold under the name "nylon 6-6", and linear polymer-caprolactam sold in particular under the name "Nylon 6".

 Moreover, complementary comparative studies have demonstrated that among the various industrially feasible structural forms, it is in the form of superficially saturated filaments of benzalkonium chloride that the best antiseptic efficacy is obtained in practical applications. The amount of benzalkonium chloride fixed for the same mass of material is all the greater as the filaments are finer. In fact, the retention capacity increases with the specific surface of the support material, and also depends on its shape.

Thus, it has been found that it is possible to fix about 188 mg of BAK per 100 g of the "SARTOLON 0.45 p" nylon 6 filtration membranes of the German company.
SARTORIUS against approximately 221 mg per 100 g of BYODINE C 0.45 "nylon 6-6 filter membranes of the so-called PALL company, and approximately 544 mg per 100 g of filter membrane" SM 11 307-050 0.45 "in nitrocellulose from the German company SARTORIUS These membranes are formed by felting filaments approximately 0.10 mm in diameter.

For wires about 0.14 mm in diameter, the fixed BAK is about 37 mg per 100 g of nylon 6 yarn, and about 55 mg per 100 g of nylon 6-6 yarn. The nylon 6 yarns set about 44 mg per 100 g in 0.4 mm diameter, 61 mg in 0.2 mm diameter and 61 mg in 0.14 mm diameter.

 In some countries, particularly in France, pharmaceutical regulations require the addition of a preservative, such as benzalkonium chloride, in solutions packaged in containers with repetitive samples. These preservatives, however, have the risk of secondary side effects, especially in eye drops. It has therefore been proposed to capture the preservative at the passage of a filter so as to dispense a purified sterile solution, but the portion of the latter remaining in the filter and the dispensing tip remains exposed to pollution between two distributions. It is the same for the downstream face of bacteriological filter membranes.

 The object of the invention is notably to overcome such disadvantages and to industrially produce antiseptic articles of constant and efficient properties at low cost.

 The invention relates to antiseptic articles, in particular for the packaging of pharmaceutical, food, cosmetic and sanitary or hygiene products, characterized in that they consist, at least in part, of a non-occlusive assembly of antiseptic filaments of a synthetic material of the group consisting of nitrocellulose, polyhexamethylene adipamide, and the linear polymer of ε-caprolactam, superficially saturated with benzalkonium chloride, at least 50 per cent by tetradecyl radical not releasable under the conditions provided for use.

 The antiseptic filaments can be assembled to form a woven, knitted, twisted or twisted wick, as well as a web formed by weaving, knitting, carding, juxtaposition / layering or felting.

 The filaments thus assembled advantageously have about 0.15 mm in diameter to ensure between them a rolling of the liquid suitable for good sterilization and filtration, with good mechanical strength. Thinner filaments can be felted to form filter membranes.

 The articles, objects of the invention may constitute in particular filter cartridges for containers or conduits of sterile liquids formed of antiseptic filaments assembled in a permeable cylindrical mass surrounded by a sealed cylindrical sheath open at both ends.

 They find a particularly advantageous application in sterile liquid packs comprising a flexible wall container whose neck is provided with a nozzle channeling the liquid outlet through a filter cartridge of antiseptic filaments.

 Such a cartridge may be constituted by a bundle of braided, twisted, and / or stranded antiseptic filaments or by a stack of fibrous washers forming a cylindrical mass sheathed in plastic material which is overmolded in a dropper tip.

 In such packages, it is generally preferable that the tip is capped with a removable cap whose bottom is lined with a sheet of antiseptic filaments which is applied against the outlet opening of the mouthpiece to seal between the liquid distributions.

 In order to ensure asepsis inside a container, or upstream of a duct, when the cartridge is not impregnated with liquid and can therefore not fulfill its antiseptic role, at least one of the ends will be provided. of the cartridge of a bacteriological hydrophilic filter membrane with pores of about 0.2 Am aperture.

 When it is desired to dispense a liquid containing an antiseptic, more particularly benzalkonium chloride, the uptake properties of this antiseptic can be used with the synthetic materials to which the invention relates while protecting the residual purified liquid from the pollution. dispensing tip. For this, according to the invention, one can equip the tip of a composite filter element whose upstream portion contains unsaturated filaments of benzalkonium chloride, and the downstream portion contains antiseptic filaments saturated with benzalkonium chloride.

 To ensure the maximum protection, the elements of the tip, other than the filaments, to be exposed to the outside and in contact with the liquid during its distribution, will be made of an antiseptic material similar to that of the filaments , and saturated with antiseptic.

 For other practical applications of the invention, the antiseptic filaments can be assembled into tufts whose base is enclosed in a frame to form a brush, for example for dental use, or a brush, for example for the application of topical skin.

 In addition to the sterile packaging of liquids, the invention has multiple and various applications: mention may be made especially of brushes, combs and brushes for hygienic or cosmetic use, dressings, surgical drapes, covers, gloves, respiratory masks, podological insoles, sterile tissues, braided tubes of sterile liquid line, various filters.

 The invention will be more clearly understood by a few examples, as well as by the examination and detailed description of the accompanying drawings, which relate to practical embodiments chosen simply by way of illustration from the many embodiments, adaptations and variants of the invention conceivable by an experienced technician.

On these drawings
FIG. 1 is an elevational view in axial section of a bottle equipped with a sterile dispensing tip according to the invention.
FIG. 2 is a view similar to that of FIG. 1, of a variant of an endpiece
Figure 3 is a view similar to that of Figure 2, another end variant;
Figure 4 and a side view of a toothbrush according to the invention
Figure 5 is a side view of a swab brush according to the invention; and,
Figure 6 is a view similar to that of Figure 1 of another variant.

 In these figures, the corresponding elements are designated by the same reference numerals, possibly assigned an index. The dimensions and the respective proportions of these elements may not be respected for a better clarity of the drawings.

 The packaging shown in Figure 1 is particularly suitable for eye drops and other pharmaceuticals. It essentially comprises a bottle 1 with a flexible wall, for example polyethylene. In its neck is inserted sealingly a tip 2, for example polyamide saturated with benzalkonium chloride dominated tetradecyl radical, terminated by a dropper mouth 4 and capped with a cap 3, for example polyamide, whose base is screwed on a thread of the base of the mouthpiece. The bottom of the cap is lined with a buffer 11 formed of an elastic ply of antiseptic filaments entangled with polyamide or nitrocellulose, saturated with benzalkonium chloride predominantly tetradecyl radical. The axial channel of the nozzle is lined with a filter cartridge 5 formed of a bundle 6 of antiseptic polyamide or nitrocellulose filaments saturated with benzalkonium chloride predominantly tetradecyl radical, assembled into a permeable cylindrical mass surrounded by a sheath cylindrical sealed 7, for example polyethylene.

 In the variant of Figure 2, the bottom of the cap 3a has a conical stud 8a which comes to marry the cavity 3a of the stilligoutte mouth of the nozzle 2a. The upstream opening of the filter cartridge 5a is sealed by a bacterial filtering membrane 9a with pores approximately 0.2 μm in aperture, welded or held by its periphery against an internal shoulder of the axial channel of the endpiece by a ring 10a, for example polyamide saturated with benzalkonium chloride predominantly tetradecyl radical, set in the axial channel of the tip.

 FIG. 3 represents another variant of a nozzle that can be adapted to the bottle of FIG. 1 for the purified distribution of a liquid conditioned with a preservative. In this variant, the cap 3b is not screwed but snapped onto the base of the nozzle 2b. The axial channel of the nozzle is lined with a composite filter element formed of a downstream filter cartridge 5b containing antiseptic filaments, of polyamide or nitrocellulose saturated with benzalkonium chloride predominantly tetradecyl radical, and an upstream filter cartridge 5'b containing sensor filaments of the preservative contained in the packaged liquid, virgin polyamide or nitrocellulose, the downstream and upstream cartridges are separated by a bacterial filter membrane 9b pore of about 0.2 Am aperture.

 For the variants of Figures 2 and 3 can be used, in particular, bacteriological filter membranes "BYODINE" or "SARTOLON" trade.

 In the tip of Figure 6, the filter cartridge 5c is formed of a stack of permeable fibrous rings 12c welded at their periphery 13c and directly overmolded in a tip 2c whose base 14c is crimped into the neck 15c of a container lc blown plastic, previously filled. This structure is particularly suitable for sterile packaging facilities with an integrated process for the manufacture and sealing of "Blow Still Seal" containers, such as those marketed under the trademark "BOTTELPACK" by the Swiss company ROMMELAG, or under the trademark "ALP" by the Automatic Liquid Packaging Company of the United States of America. A cap 3c, screwed, whose bottom is lined with an antiseptic buffer llc, protects the tip, it is itself sheathed in an extension 16c of the neck of the bottle made at the same time as crimping, connected to the crimped portion by a frangible zone 17c which breaks at the first unscrewing of the cap and thus constitutes a guarantee of non-prior use for the user.

Filter cartridges and other antiseptic articles which are the subject of the invention may be made using conventional wire working techniques, in particular as described in the following examples.
Example 1 - Tressaae: a primary tubular braid approximately 0.4 mm in diameter is first formed by braiding together 12 strands of wire 15/100 mm in diameter. Twelve primary braids were then braided together to form a cylindrical braid of about 2.5 mm which was encapsulated by peripheral annular extrusion of the same material to form a sheath about 4 mm in diameter with a radial thickness of about 0 mm. , 8 mm. Then cut into cylindrical sections to the desired length, for example about 20 mm for the filter cartridges 5, 5a of Figures 1 and 2 and about 10 mm for the cartridges 5b, 5'b of Figure 3.

 Example 2 - Toronaae: a cylindrical primary strand approximately 0.84 mm in diameter is first formed by twisting 21 strands of yarn 14/100 mm in diameter together. A primary strand is used as an axis to twist together 6 other primary strands to obtain a cylindrical strand about 2.5 mm in diameter which is coated by extrusion of translucent low density polyethylene forming a sheath of about 4 mm. diameter with a radial thickness of about 0.8 mm. Then cut into cylindrical sections to the desired length for the intended application.

 Example 3 - Carding: in a conventional machine of the "RANDO WEBER" type, a nonwoven web is prepared by aerated carding of sections of polyamide filaments of about 15 to 30 mm in length and about 0.13 to 0.16 mm in length. diameter of which at least a portion are curled. Monomer of the same polyamide is sprayed into the web to join the filaments together only at their points of intersection and polymerized to obtain a filterable web which can be used, after saturation with benzalkonium chloride, for non-woven antiseptic textile applications. Cutting such a slab into slices, for example by ultrasonic welding of the slices allows for the pad 11 disposed at the bottom of the cap 3 of the packaging of Figure 1, and the washers 12c of the packaging of Figure 6.

 Example 4 - Juxtaposition / Sunposition: A sheet of adjacent contiguous turns of polyamide filaments is deposited on a drum which is covered by deposition of at least one analogous non-parallel orientation sheet. A homogeneous sheet of crossed filaments is thus obtained which is cut into slices which are stacked to form a filter cartridge overmoulded directly or after sheathing in a tip, such as that of FIG. 6.

Example 5 - Imprecnation: A solution of benzalkonium chloride in the aqueous solvent of the liquid to be conditioned is used. Thus, for eye drops, a solution of benzalkonium chloride at a concentration of 100 g / ml in an aqueous solution of
NaCl at 0.9 g% (pH 7.2). The filaments or other articles to be saturated in this excess solution are soaked for about 2 hours at normal ambient temperatures and pressures, then, after draining and drying, they are washed with a 0.9 g% aqueous NaCl solution (pH 7.2) until disappearance of benzalkonium chloride in the effluents. Drain and dry at a temperature below about 1100C.

When using a 60/40 standard 60/40 benzalkonium chloride (BAK) solution with a duodecyl radical (BAK C12) and a 40% tetradecyl radical (BAK)
C14) is found in the BAK fixed on polyamide proportions of BAK C12 and BAK C14 ranging from 50/50 to 40/60 which reveals a greater affinity of polyamides for BAK C14, all the more interesting as the BAK C14 has a higher bactericidal activity than BAK C12.

To determine the amount of BAK fixed on polyamide filaments or other supports, it is extracted three times by stirring at room temperature in a solvent mixture of 40 parts of methanol and 60 of aqueous solution of anhydrous sodium acetate. distilled water (8.5 g / l), adjusted to pH 5.0 with acetic acid for 30 minutes, with 2 ml of solvent per 100 mg of polyamide. The washing solvents are then conventionally analyzed with a high pressure liquid chromatograph, such as the one sold under the name HEWLETT PACKARD 1050, with recorder.
HELWETT PACKARD 3390 A and WATERS column (3.9 x 150 mm) y
Bondpak CN-lOssm-Ref. 86688. After calibration, the calculations are made from the peak areas corresponding to the
BAK C12 and BAK C14. It is thus possible to control both the total amount of BAK fixed (C12 + C14) and the relative proportions of BAK C12 and BAK C14.

Claims (13)

 1. Antiseptic articles, in particular for the packaging of pharmaceutical, food, cosmetic and sanitary or hygiene products, characterized in that they consist, at least in part, of a non-occlusive assembly of antiseptic filaments of a synthetic material, of the group comprising nitrocellulose, polyhexamethylene adipamide, and the linear polymer of ε-caprolactam, superficially saturated with benzalkonium chloride, at least 50 percent of non-releasable tetradecyl radical under the intended conditions of use.  2. Articles according to claim 1, characterized in that the antiseptic filaments constitute a web formed by weaving, knitting, carding, juxtaposition / superposition, or felting.  3. Articles according to claim 1, characterized in that the antiseptic filaments are assembled in wick plait, knitted, stranded or twisted.  4. Articles according to one of claims 1 to 3, especially filter cartridges for containers or conduits of sterile liquids, characterized in that they consist of antiseptic filaments, assembled into a longitudinally permeable cylindrical mass surrounded by a cylindrical sheath watertight open at both ends.  5. Articles according to one of claims 1 to 4, in particular packages of sterile liquids, characterized in that they comprise a container (1) with a flexible wall whose neck is provided with a nozzle (2) channeling the outlet liquid through a filter cartridge (5) of antiseptic filaments (6).  6. Articles according to one of claims 4 and 5, characterized in that the cartridge (5) is constituted by a bundle of antiseptic filaments (6) braided and / or twisted forming a cylindrical mass sheathed plastic which is overmolded in a butigoutte mouthpiece 2.  7. Articles according to claim 6, characterized in that the filaments are about 0.15 mm in diameter.  8. Articles according to one of claims 4 and 5, characterized in that the cartridge is constituted by a stack of permeable fibrous rings 12c, tubularly sheathed plastic over-molded in a dropper tip.  9. Articles according to one of claims 6 to 8, characterized in that the tip is capped with a cap (3) removable whose bottom is lined with a web (11) of antiseptic filaments which applies against the opening (4) outlet of the nozzle (2) to close it between the liquid distributions.  10. Articles according to one of claims 4 to 8, characterized in that at least one end of the cartridge (5) is lined with a filter membrane (9a) hydrophilic bacteriological pore of about 0.2 ym opening.  11. Articles according to one of claims 4 to 10, characterized in that the cartridge contains a composite filter element whose upstream portion (5'b) is formed of unsaturated filaments of benzalkonium chloride and the downstream portion (5b ) of filaments saturated with benzalkonium chloride.  12. Articles according to one of claims 5 to 11, characterized in that the elements of the tip, other than the filaments, to be exposed to the outside and in contact with the liquid during its distribution are made of an antiseptic material similar to that of the filaments.  13. Articles according to one of claims 1 and 3, characterized in that the antiseptic filaments are assembled in tufts whose base is clamped in a frame to form a brush or a brush.