FR2701397A1 - Product for topical administration of medicinal or cosmetic substances - Google Patents

Abstract

Product for the topical administration of medicinal or hygienic substances, characterised in that it is made of a cheesecloth made of nonwoven textile fibres. The product, that is to say a cheesecloth made of nonwoven polyamide or polyester (PET) or polypropylene fibres in particular, impregnated with active solute, packaged chiefly in ready-for-use heat-welded unit-dose sachets, is particularly intended for the administration of medicines (Art. L 511 of the Public Health Code) on the teguments and the mucosa and especially in neonatology and in the pharmacotherapeutic class of dermatology, and for the application of cosmetic products (Art. L 658-1 of the P.H.C.). The invention is characterised by the use of nonwovens which are absorbent by capillarity, made of fibres which are nonabsorbent with regard to the pharmaceutical use, tangled and calendered, exhibiting comfort characteristics in use and enabling a protocol of investigations of container-content interaction to be established especially because of the specifiability of the polyamide, polyester (PET) or polypropylene fibres.

Description

DESCRIPTION
The technical field of the invention is that of GALENICS or pharmacotechnology which aims to "find for each active substance the drug presentation best suited to the treatment or prevention of a specific disease".

The invention relates to the production of ready-to-use impregnated stamens intended for application to the integuments and mucous membranes of active medicinal or hygienic solutes.

"ETAMINE" is the term chosen - little used, meaning "light veil" - to designate what is called by use by quasi-barbarism "towel" or wipe ".

The invention relates to the use of an absorbent non-woven veil made with non-absorbent synthetic fibers.

The nonwoven veil is impregnated with active solute and packaged in ready-to-use dose sachets.

The impregnated nonwoven sails can be packaged in bulk - ready-to-use - in containers.

The invention relates in particular to the use of nonabsorbent fibers of
POLYAMIDE, POWESTER and POLYPROPYLENE.

The fibers of POLYAMIDE, POLYESTER or POLYPROPYLENE are used by the textile manufacturer to form nonwovens residing in veils of scrambled and bonded fibers.

The fibers are scrambled by carding in the case for example of POLYAMIDE and POLYPROPYLENE and then bonded by calendering, that is to say thermobonded. the fibers are scrambled and bound by a jet of water in the case for example of POLYESTER.

The veils of tangled nonabsorbent fibers are impregnated by simple capillarity.

The nonwoven sails used in galenics are in the form of rolls which are then cut into "stamens" to size, then impregnated with the aid of metering pumps of the determined quantity of active medicinal or hygienic solutes. For presentations in single sachets: 'é1: amino is introduced folded into the 3-sided welded sachet and is impregnated, after inie' * lon the dose in the sachet. As an example, pre-impregnated stamens can be conditioned in number in a container.

The stamens impregnated with POLYAMIDE, POLYESTER and
POLYPROPYLENE in particular are intended for the administration of drugs (
Art. L 511 of the Public Health Code) and the application of cosmetological products (Art. L 658-1 of the CSP)
In the state of the art and pharmaceutical technique it is the absorbent fibers which are used or described and specified in the Pharmacopoeia.

The applicators (that is to say tampons or compresses) are then temporarily impregnated with active solutes.

When the applicators (tampons or compresses) are prepared in advance, they are in the form of absorbent fiber fabrics (gauze, compress, tulle)
The families of absorbent products produced with absorbent fibers described are the following: - hydrophyl cotton - hydrophyl cellulose wadding, - hydrophyl cotton gauze - hydrophyl viscose wadding, - hydrophyl cotton tulle, - compresses impregnated with hydrophyl cotton nonwoven etc ...

These traditional families of products are used for the ability of the body of fibers to absorb in themselves the active medicinal or hygienic solutions.

In the state of the art and of the pharmaceutical technique in particular, the topical active solutions are administered using pads or compresses made of absorbent tissue, made with absorbent fibers: in the following pharmaco-therapeutic areas: - anesthesia of contact, - dermatology {(dermocortocoides, local antibacterials, local antifungals, antiacnefics, wound detergents, local seborrhea inhibitors, local antipruritics, kerotolytics (corricides, verrucides), psoriasis, rosacea, local antimitotics, topical trophic action, antialopecics, local anticouperosics, antiphotosensitizers ...), - topical proctology (hemorrhoidal pathology), - external antiparasitics, - repellents in rheumatology and pneumology, - anti-inflammatory drugs in rheumatology, - stomatnlogy etc ...

involving several dozen pharmacologically and chemically active molecules from different families.

To "find for each active substance the drug presentation best suited to the treatment or prevention of a specific disease" corresponding to the nonlimiting list of pharmacotherapeutic classes established above, the problems which are in particular to be resolved by the galenist are the following: - search for the product or device capable of avoiding contamination of the active solute (possibly sterile) during each use. In non-unitary presentation (bottle for example) the solute is contaminated by simple exposure to the open air and moreover by contact with the applicator if it is a cotton ball taken in a sachet.

- the applicator-applied substance compatibility, ie container-content interaction ", - the stability of the active solute because the active solutes have a duration of stability in closed packaging before use different from that after use, ie after opening of the packaging and venting of the active solute, - the absorption capacity of the applicator used and its capacity for restoring the active solute during its application (for pharmacotechnical reasons and therefore for economic reasons , linked to the impregnation of the applicator with the most suitable dose of active solute.

- patient comfort. Indeed it is a question of avoiding the use of "textiles" considered too aggressive when it is a premature, the eyelid of a newborn, sensitive mucous membranes in a particular way and d 'generally because the galenist must find the least aggressive and least traumatic form of administration possible - the entire SPECIFICABILITY of the textile fibers used. We hear by
SPECIFICABILITY the ability to specify.

The model of pharmaceutical specifications (ie specification) is defined by the MONOGRAPHS as conceived by the National Pharmacopoeias including the French Pharmacopoeia, comprising characters, identification reactions, impurity limit tests, dosages, etc. - l use of substances, excipients or articles described in the Pharmacopoeia when the Pharmacopoeia Monographs are enforceable.

specifications are established in the French Pharmacopoeia, in particular under the following Monographs: * for POLYAMIDE (polyamide packaging sheets, polyamide 6 yarns, polyamide 6-6 yarns, polyamide 6, polyamide 6-10, polyamide 1 1 for sheets and for molding ...), ** for POLYESTER (polyethylene terephthalate packaging sheets, polyethylene terephthalate threads, polyethylene terephthalate ...), *** for POLYPROPYLENE (polypropylene for containers intended for parenteral preparations),
No Pharmacopee describes nonwovens of POLYAMIDE, POLYESTER, or POLYPPxOPJT / ENE in particular.

In the state of the art and technique, the TEXTILE industry manufactures many varieties of nonwovens, in particular of POLYAMIDE fibers,
POLYESTER and of: POLYPROPYLENE.

To date, there are no manufacturing operations reserved for the galenic use of nonwovens of POLYAMIDE, POLYESTER and POLYPROPYLENE in particular.

Nonwovens find many applications in the most diverse fields: - use of POLYAMIDE 6 fiber nonwoven for making clothing linings, - use of POLYPROPYLENE or POLYESTER fiber nonwovens in furniture, clothing. .

and generally used in electronics, agriculture, automobile etc ...

The textile industry produces a wide variety of sails in nonwoven fibers, simple or mixed, untreated or treated using technological additives such as lubricants, binders, thermal stabilizers, antioxidants, reinforcing agents etc ... (non-exhaustive list ).

The nonwoven sails made of POLYAMIDE or POLYPROPYLENE fibers are made dry by scrambling the fibers then bonding by calendering (thermobonding) without the use of any technological additive for example;
POLYESTER nonwoven sails are made by scrambling using water jets then binding by calendering without using any additives for example.

As an example of the manufacture of nonwovens, the following schematic description of the process for manufacturing nonwoven web coils of polyamide 6 fibers follows: * reception of bales of packaged and identified fibers (identity check, labeling check, check of conformity ...) ** decompacting of the bales on bale breaker (prior cleaning control, hygrometry control ...) *** conveying by fiber air flow **** fiber storage and flaking * **** combing the fibers (with two upper and lower cards) ****** transfer of the sheet in two scrambled veils ******* calendering (thermobonding with temperature and calendering speed control) * ******* winding of the sheet on reel then exit of the reel on carriage, packaging of the reel, transfer of the reel for cutting, cutting, packaging and storage awaiting shipment
This diagram describes a manufacturing process without recourse to any technological additive and should not be retained as limiting of the possible processes.

There is also a method of bonding polyester fibers by acrylic binder.

The technical problems which arise for the galenist with regard to the use of nonwoven textile products are as follows: - assurance of a specified manufacturing process allowing the reproducibility of the determined quality, - the existence of manufacturing processes which do not require to no technological additive such as lubricants, binders, stabilizers, antioxidants for example, - the SPECIFICABILITY of the POLYAMIDE, POLYESTER or POLYPROPYLENE used for the manufacture of fibers and then the nonwoven veil by the textile industry, - hydrophobicity or negligible absorption of POLYAMIDE, POLYESTER or POLYPROPYLENE fibers in particular: with regard to pharmaceutical use, - absorption capacity of nonwovens of POLYAMIDE, POLYESTER or POLYPROPYLENE fibers in particular; and the capacity for restoring the active solution during the application of the impregnated nonwoven fabric on the integuments and mucous membranes, - comfort of use of the applicator in newborns in particular and on sensitive mucous membranes, - possibility of impregnation stamens in nonwovens by true solutions, suspensions, aqueous, hydroalcoholic or other solutes of fluid, semi-fluid or other consistency, emulsions or others.

The invention resides in the use of a nonwoven of POLYAMIDE, of POLYESTER or of POLYPROPYLENE in particular, which remedies: - the drawback of non-absrbarcedu the support to impregnate active solutes in the sense that the veils of nonwoven POLYAMIDE , POLYESTER or
POLYPROPYLENE is impregnated by simple capillarity: * for example a non-woven veil of POLYAMIDE 6 with a dimension of 13 cm
X 12 cm weighing 0.54 g. dry, impregnated and drained contains 1.5 to 2.5 ml of active solute, ie an absorption capacity of 300 to 500 percent. These figures are given by way of example and cannot constitute a standard or exhaustive results of experiments.

* by way of example, a nonwoven veil of POLYESTER (PET) with a dimension of 13 x 12 cm weighing 1.14 g dry, impregnated and drained contains 8 to 9 ml of active solute. These values cannot constitute a standard or an optimum result and are given by way of example of the absorption capacity of nonwoven webs produced with nonabsorbent fibers.

- the drawback of absorbing the active solute in the body of absorbent fibers in the sense that the fibers of POLYAMIDE, POLYESTER or
POLYPROPYLENE are non-absorbent with regard to pharmaceutical use: POLYAMIDE is used for the manufacture of syringes, IUDs, mitral valves, bags, threads. The nonabsorbent nature of the polyamide is allowed in pharmaceutical use.

The recovery in humidity - which begins at the end of the manufacture of the fibers - at 10 C and 65% relative humidity is 3.5 to 4.5% (source: Institut Textile de
France) (values: Polyamide 6).

These values do not constitute a standard or limits for the acceptability of fibers used for making nonwovens for the manufacture of impregnated stamens for the application of medicinal or hygienic solutions.

POLYESTER is used for the production of bags, threads, tubular knits for vascular prostheses, of the larynx, of the esophagus in particular. The nonabsorbent nature of POLYESTER (PET) is allowed in pharmaceutical use.

The recovery in humidity - which begins at the end of the manufacture of the fiber - at 10 C and 65% relative humidity is about 0.4% (source: Textile Institute of
France)
This value is given in the same way for reference without constituting a standard or limit of acceptability.

POLYPROPYLENE is used for the manufacture of syringes, vials of serum, bags ... Its non-absorbent character is allowed in pharmaceutical use. The recovery rate under the conditions cited is 0.05 percent. This value does not constitute a standard or an acceptability limit for fibers for use mentioned above.

- the disadvantage of NON-SPECIFICABILITY of material used in the sense that the
POLYAMIDE, POLYESTER and POLYPROPYLENE in particular are known and specifiable chemical bodies: POLYAMIDE is the name of the family of polymers characterized by the amide bond resulting from the condensation of an organic acid group on an amine. POLYAMIDES are designated by the number of carbons in their constituents. In the family of polyamides retained POLYAMIDE 6, the
POLYAMIDE 12 and polyamides 6-6, 6-10, 6-12, 11. For example POLYAMIDE 6 is poly (imino / oxo 1 hexamethylene) obtained by polymerization of epsilon-caprolactam or 2H-azepinone-2 hexahydro .

POLYPROPYLENE is a propylene homopolymer or a propylene copolymer containing up to 20% ethylene. The linear chains consist of propylene units in the case of a monomer or of alternating propylene and ethylene units in the case of copolymers.

POLYESTER (PET) is the common name for POLY (TEREPHTHALATE
ETHYLENE) which is the poly (oxyethyleneoxyterephaloyl) obtained by polycondensation of terephthalic acid and ethylene glycol or by transesterification between methyl terephthalate and ethylene glycol followed by polycondensation.

The powders or granules of POLYAMIDE, POLYESTER (PET) and
POLYPROPYLENE in particular, are transformed into fibers mainly by extrusion using technological adjuvants (lubricants in particular) which will have to satisfy limit impurity tests and skin and eye safety tests.

- the drawback of the necessary use of technological additives during the transformation of fibers into nonwovens by the textile industry, in the sense that nonwovens of fibers of POLYAMIDE, POLYESTER or PeLN'PROPYLENE can be scrambled and bound without use of no technological aid.

- the drawback of retaining the active solute in the applicator in the sense that the active solute is returned in an effective amount when it is used on the integuments and mucous membranes. For example, a nonwoven veil of fibers of
POLYAMIDE 6 with a dimension of 12 cm x 13 cm impregnated with 2.5 ml of active solute returned during its application on 100 cm 2 of hairless skin 2 ml of active solute. These values cannot constitute a standard or an acceptability threshold for a nonwoven cheesecloth - in nonabsorbent fibers of POLYAMIDE, POLYESTER (PET) or POLYPROPYLENE in particular, impregnated with active solute for pharmaceutical or cosmetic use.

The invention resides in the use of a nonwoven of POLYAMIDE fibers,
POLYESTER (PET) or POLYPROPYLENE in particular, for the manufacture of stamens impregnated with aqueous active, alcoholic, hydrolacoolic solutes etc. of liquid, fluid, semi-fluid consistency, impregnated by capillary action and intended for the administration of medicaments or for the application of cosmetics on the integuments and mucous membranes.

The impregnation of stamens in nonwoven POLYAMIDE, POLYESTER,
POLYPROPYLENE in particular, can be produced industrially using metering pumps with commercially available equipment and packaged on the same machine in unit dose sachets in ready-to-use heat-sealed paper / PE / aluminim / PE complex.

The impregnated stamens can be presented in number, packaged in a multipurpose container.

I following diagram without being limiting and exhaustive is given only by way of illustration of the invention.

MANUFACTURE OF POLYAMIDE 6 NONWOOD STAMINS
IMPREGNATED WITH PHYSIOLOGICAL SERUM
PACKAGED IN UNIT BAGS
FOR NEWBORN EYE CARE
Polyamide / chemical body
chemical industry raw material
Synthesis of polyamide 6 by polymerization of 1 epsilon-caprolactam. Production of polyamide 6 in powder or granules (without coloring agent),
* control of precursors
* control of the finished product: identity, characteristics, tests, impurity limit tests according to specifications. certificate of conformity.

Polyamide / fiber
chemical industry raw material
Manufacture by extrusion of 1.7 Dtex fibers, 3.8 mm long uncoated,
* control of polyamide 6 powders or granules upon receipt,
* control of the finished product: approval, characters, tests, mechanical tests, limit tests according to specifications. certificate of conformity.

 * control of skin and eye safety in rabbits of the technological additive used during manufacture. safety certificates.

Polyamide / textile product
textile industry raw material
Manufacture of a nonwoven veil of 35 g./m2 by dry scrambling of polyamide 6 fibers without mixing and calendering (thermobonding) the fibers within the limit of approximately 21% of bonded surface.

* control of polyamide 6 fibers upon receipt,
* control of finished product: identity, mechanical tests, percentage of bound surface, inclusions, according to specifications. certificate of conformity to the specifications.

Impregnated stamens / pharmaceutical product
Injectiott of 2ml of aqueous NaCl solute at 9 / m / v in a sealed bag 3
sides in which a 12cm x 13cm cheesecloth has just been introduced
non-woven polyamide 6 with a grammage of 35g./m2, folded on itself.

 Welding of the bag. (note: impregnation takes place in the sealed bag).

* control upon receipt of the non-woven polyamide 6 veil according to monograph (identification, characters, mechanical tests, tests, limit tests ...),
* controls during production (cutting size of the stamens, volume of solute injected, sealing of the paper / PE / aluminum / PE sachets ...

according to Standard Operating Procedures and monographs),
* control of finished product: analytical tests, pharmaceutical tests of extractable volume, tightness according to monograph,
STERILIZATION of the impregnated, bagged, sutured stamens by ionizing radiation at a dose of 15 kGy: analytical tests after exposure to radiation, sterility test. Batch release.

Claims (6)

(1) Product for the topical administration of drugs (Art. L 511 of the CSP) or cosmetological products (Art. L 658-1 of the CSP) characterized in that it consists of: - a fiber stamen nonwoven textiles, non-absorbent with regard to pharmaceutical use, - a substance with pharmacological or cosmetic effect impregnated in the cheesecloth by capillary action. (2) Product for topical administration according to claim (1) characterized in that the textile fibers are made of POLYAMIDE (polyamide 6 or polyamide 12 or polyamide 6-10 or polyamide 6-12 or polyamide 11). (3) Product for topical administration according to claim (1) characterized in that the textile fibers are made of POLYESTER (polyethyl terephthalate)). (4) Product for topical administration according to claim (1) characterized in that the fibers are made of POLYPROPYLENE. (5) Product for topical administration according to claim (1) characterized in that the substances are in the form of true solutions, suspensions, emulsions, collol dales, aqueous, alcoholic, hydroalcoholic solutions, fluid or semi-fluid. (6) Product for topical administration according to claims (1) (2) (3) (4) characterized in that the nonwoven veils have the galenic characteristic of softness and silky.