CA1190207A - Absorbent dressing and process for producing same - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
An absorbent dressing, which is atoxic, compatible with the tissue and well adapted to the shape of the wound and can be easily removed again, protects the wound against infections and confines it in that it absorbs bacteria, fungi, toxins, proteins and inflammation mediators and which thus is suitable for covering intensely oozing infectious wounds as well as affected areas in skin and tissue diseases, consists of potentially macroporous particulate mixtures of regenerated cellulose and a polysaccharide derivative con-taining carboxylate groups. For producing said dressing viscose solutions containing the admixed polysaccharide derivative are thermally coagulated after shaping, purified and dried.

Description

The present inventiorl relates to an absorbent dress-ing to be used for covering and cleaning intensely oozing infectious wounds and affected areas in skin and tissue diseases and to a process for producing same.
It i5 known that a modern dressing which can be used for defec-t wounds of variable genesis, but particularly also for problem indications such as Ulcus cruris, decubital ulcers, diabe-tic gangrene, chronically infected wounds and second- and third-degree burns, must be toxicologically un-objectionable, immunologically compatible, producible withoutproblems, storable and sterilizable. Furthermore, for the ventilation of the wound a modern dressing must have an ade-quate permeability to gas, it must properly adhere to the wound surface wi-thout sticking to the scab of the wound and it must have a high absorptive power for factors interfering with the wound healing process such as wound exudate, bac-teria, and necrotic cell material. It must have an intensive wound-cleaning effect and thus confine and prevent infections and in addition it must promote granulation and/or epitheli-zation. It is also known tha-t conventional dressings, which usually are fabrics and materials of natural or synthetic - fibres, primarily of regenerated cellulose in the form of short or long fibres, satisfy these requirements only to a very incomplete extent. In particular, they stick to the wound or wound scab so that when changing the dressing the protective scab is torn open, the healing process is inter-rupted and naturally extended. Furthermore, the absorptivity of conventional dressings is limited so that particularly bacteria are not absorbed, This has the result -that frequent-ly it is only possible to confine the infection with theadditional use of antibacterial active substances such as antibiotics or sulphonamides. To overcome these disadvantages there were developed dressings as disclosed for example in DDR Patent 97,547, German Offenlegungsschriften 1,2Q9,702, 1,254,295, 1,492,409 and 1,629,425, and U.S. Patents 2,923, 298, 3,012,918, 3,043,301, 3,285,245, 3,434,472, 3,438,371, 3,441,021, 3,446,208, 3,457,919, 3,579,628 and 3,750,666, whlch are underlaid on the side of the wound with a non-adhesive, flexiBle perforated plastic sheet of polyethylene, polypropylene, polyvinylchloride, polyvinyl acetate, poly-ethylene terephthala-te, e-thylene/vinyl acetate copolymers, polyacrylates or polyvinyl pyrrolidone. Dressings which have on the side of the wound similarly acting thin, perfor-ated metal foils of silver, aluminium or zinc instead of the perforated plastic sheets are also known for example, from German Offenlegungsschriften 1,161,384 and 1,417,379 and U.S. Patent 2,934~066. These dressings do not stick to the wound but they let the wound exudate pass through the perfor-ations and this exudate can be absorbed by the subse~uent absorbent layers such as cellulose, press cotton, cotton felt.
Apart from the fact that the absorptivity of these dressings is fundamentally not increased the greasy-purulent exudate of intensely infected wounds clog the openings so that exudate pockets providing excellent growth possibilities for bacteria are forming. The metal-underlaid dressing foils have a further disadvantage, namely that a chaffing effect cannot be excluded entirely.
An increased absorp-tivity of the dressings is attained by the use of natural or synthetic materials which are insoluble in water but do not swell with water. These materials are, f~r example, chitin and chitosane. (MIT Sea Gran-t Rep. MIT SG 1978, Proc. Int. Conf. Chitin/Chitosane 1977, page 296-305), collagen (DDR Patent 56,587, British Patent 1,195,062, U.S. Patents 3,471,598, 3,491,760, 3,80Q,792, 2Q~

3,939,831 and 4,089,333~, wet cross-linked cellulose fibres, particularly formalized co-tton and rayon fibres (German offen-legungsschrift l,~g2,365) which suitably still contain 5 to 20~ by mass oE the Na salt of.carboxymethyl cellulose (CMC~
(Cerman Offenlegungsschrift 2,638,6541, mixed fibres of cellulose regenerate and Na-CMC (V.S. Patent 3,858,585) and cross-linked C~C products (German Offenlegungsschrift 2,357, 079), hydrolysis products of cross~linked copolymers of vinyl esters and unsaturated carboxylic acids (German Offen-legungsschrift 2,653,135~, cross-linked polyacrylamides and sulphonated polystyrenes (German Offenlegungsschriften 1,617, 998 and 1,642,072, U.S. Patent 3,669,193), cross-li.nked poly-N-vinyl pyrrolidones and morpholinones (U.S. Patent 3j810, 648~, cross-linked dextrans, starches, dextran and starch derivatives (DDR Patent 109,513, German Offenlegungsschrift

2,403,269~ and foamed plastics from urea/formaldehyde and melamine/formaldehyde resins (German Offenlegungsschriften 1,246,173 and 1,247,553), which can additionally contain butadiene/styrene or butadiene/acrylo-nitrile copolymers (U.S. Patent 3,314,425), and foamed plastics from polyurethane (Deutsche Offenlegungsschrift 2,103,590, British Patents 1,065,994, and 1,253,845, U.S. Patents 3,157,178, 3,648,692,

3,975,567 and 3,978,955). The hydrolysis products of the cross-linked vinyl acetate/methacrylate copolymers can absorb for example, up to 100 times their weight Oc water and wound exuda-te, the cross-linked polyacrylamides up to 70 times their weight and the cross-linked poly-N-vinyl pyrrolidones at least 15 times their weight.
~ost of -the dressings are fabrics or materials of fibre-like products, i,e., they are used in the form of flat shaped articles. Covering wound with particular materials such as dusting powders or the like is applied comparatively seldom although in case of uneven and fissured wounds these powders show great advantages as compared with the flat shaped dressings, Particular materials suitable for covering wounds are described, for example, in the German OEEenlegungsschrift No. 2,4Q3,26~ They are microbeads of cross-linked polysac-charides and polysaccharide derivatives, particularly of cross-linked dextrans, which are applied directly to the wound. It is also known that spherical regenerated cellulose particles can be used for the same purpose. These two mat-erials have a high sorptive power for wound secretions and can also remove bacteria, fungi, toxins, inflammation media-tors (prostaglandines) and plasma proteins (fibrogen cleavage products) from the surface of a wound.
Despite many evidently pOSitive properties these two particular materials also have a number of disadvantages which limit their use on a wide scale. The particles, which are constructed from cross-linked dextrans and whose gel matrix has no real pores neither in the dry state nor in the moist state, swell upon contact with water and aqueous solu-tions while their volume substantially increases and produce a gel layer, wherein the permeability to gas is reduced. This disadvantage is actually overcome in the generated cellulose particles which have a macroporous structure and thus absorb water without any swelling, but it is exactly their porosity which causes nonaqueous media, for cxample, organic solvents, to be absorbed and this can have an unfavourable effect in specific forms of application. Furthermore their steriliza-tion with ~ rays is associated with a yellow to brown colora-tion. The particular material mentioned above can be pro-duced by means of conventional processes, the cellulose par-ticles, for example, by acidifying emulsified cellulosc D2~

- solutions (Swedish Patent 382,066, U.S. Patent 3,597,350~, by instilling viscose solutions lnto suitable coagulating baths (Japanese Paten-ts 73.21738l 73.4082 and 73.607S3), by short-time heatlng particulate cellulose esters, as for example, cellulose aceta-te, in silicone oil to 290-300C
(Japanese Patents 78.07759 and 73.86749) or by -thermal coagulation of viscose dlspersions (Czechoslovak Pa-tent 172,640, DDR Patent 118,887, German Offenlegungsschrift 2,523,839, U.S. Patent 4,055,510). However, the cellulose particles obtainable according to this process provide an absorbent dressing of the above quality only when they are so dried that their microporosity is mai.ntained. According to the prior art this can be achieved only with special dry-ing processes whi.ch are cumbersome and economically unfavour-able.
Therefore, the present invention provides a dress-ing which is atoxic and tissue-compa-tible and can be readily adapted to the shape of the wound and to the skin and tissue portions concerned and even to uneven and fissured wounds and which rapidly removes the exudate from intensely oozing wounds and is easy on the patient, that is to say, a dressing which also binds bacteria, fungi, toxins, proteins and pros-taglandins, in addition to the exudate, and is sterilizable and resterilizable and promotes granulation and epitheliza-tion but which moreover tends to swell only to a minor extent due to its trueand laten-t macroporosity so that the permea-bility to gas of the layer covering the wound remains substan-tially unaffected, and finally which is economically advan-tageous due to a favourable basi.s of raw materials and a simple method of production and can be applied on a wide scale.
Taking into account the raw material situation and the good experience with particulate materials the present invention provides a dressing which has the above quality and is based on cell~lose moldings as well as a process fo~
producing same.
It has been surprisingl~ found that dry particulate products of mixtures of regenerated cellulose and a carboxy-late-groups-containing polysaccharide derivative, referred to hereinaEter as polysacchari:de derivative, provide a dress-ing oE -the desired quali-ty. This is further surprising be-cause the polysaccharide derivatives mixed with the regener-ated cellulose are plasma coagulating per se and have anhaemostatic eEfect. This should result in undesired incrust-a-tion. However, this kind of incrustation does not occur.
The particula-te products applied to -the wound can be spheri-cal par-ticles or granulates having a diameter > 10~. They absorb aqueous wound secretes of any consistency and with them also bacteria, fungi, toxins, proteins and inflammation mediators rapidly and substantially without pain so that wound infections are confined or prevented and the wound dries rapidly but remains elastic. The granular structure of the particles, which is also retained in the exudate-saturated state, also stimulates the granulation and epithelization.
The high inherent stability, which is attained by the compar-atively slight swelling of the particles, assures good venti-lation of the wound.
The polysaccharide derivatives, mixed and molded with regenerated cellulose, result in the dressing according to -the present invention, must be at least 50% soluble in water. For example, sodium carboxy-methyl cellulose, sodium carboxy-methyl starch and sodium alginate are suitable. Their proportion in the polymer mixture is 3 to 30~.
As compared with the spherical particles of pure regenerated cellulose the particulate products from mixtures of regenera~e cellulose ~d polysaccharide derivates i.e., the products accoxding to the present invention, are distinguish-ed in that the dryin~ step required according to the produc-tion process can be carried out in a conventional manner.
In fact the originally present system of pores collapses while the particles are shrinking, but upon wetting with water under conditions of application the pore system is substantially regenerated so that not only do the particles equal -the pure cellulose particles in their sorptive power but they even exceed them.
The hydrophilic character of the polysaccharide derivatives used and their chromatographic separating power are additionally noticeable in a positive manner.
While the pure cellulose particles can absorb germs only into the interparticulate capillary spaces, wherein they are retained only relatively loosely, the special internal structure of the particles according to the present inven-tion and the ionic character of the polysaccharide derivatives cause a substantially more rigid bond. A further advantage lies in that the capability of absorbing water and the kine-tics of water and exudate absorption can be adjusted withinrelatively wide limits over the production process and that a better adaptation to various requirements thus is possible.
~ further substantial advantage is that the par-ticulate products according to the present invention retain their positive effect even in the presence of glycerol or polyalkylene glycols, enabling the production of pasty pre-parations. Furthermore it has been found that by using small amounts of glycerol or polyethylene glycol, preferably 5 to 30%, damage in -the radiation~chemical sterilization can be plevented. This damage would otherwise occur associated with a deterioration of the produc-tion parameters and with yellow coloration.
~ 7 -The particulate products according to the present inventian are usually appl1ed to the wound in a layer thick-ness of up to Smm and, when required, secured by a light conventional pressure bandage. The change of dressing, which should be carried out after the saturation of the particles with wound exudate but not later than after 14 to 20 hours, is very simple and easy, for example, by rinsing the particle layer with water or normal saline solution and by applying the particulate material once more.
According to the present invention the dressing is obtained by a method in which a technically conventional vis-cose solution is mixed with a polysaccharide derivative hav-ing the above specification in an amount of 5 to 50~ relative to the total mass of polymer mixture in the viscose solution, this mixture is thermally coagulated and the coagulate is purified, wetted with 5 to 30% of polyalkylene glycol and dried.
The particulate structure of the products can be produced prior to and after the coagulation. In a particular embodiment the particles are produced by a method in which a viscose solu-tion containing the additional polysaccharide derivative is dispersed dropwise in a suitable conventionaI
mannex, for example, by dispersing in an organic liquid im-miscible with water and thermally coagulated and regenerated by heating to temperatures of 50 to 100C within 30 to gO
minutes.
In a further embodiment of the process of the pre~
sent invention the viscose solution containing the polysac-charide derivative is treated under comparable conditions but without preceding fine dispersion and the coagulate is obtained in the form of plates, rods or blocks, which are then mechanically comminuted in a suitable manner.

~ fter washing and drying the finely divided c~umbs powdery granular products are obtained, When required, these products are sub~ected to dry grlnding in order to attain the deslred particle size spectrum.
To purlfy the particulate products thus obtained and simultaneous].y to control their properties they are sub-jected -to a number of washlng operations with low molecular alcohols, prefexably methanol, or ethanol, or ketones, pre-:Eerably acetone, with aqueous solutlons of these alcohols and~or ketones and~or with water or aqueous solutions, as for example, dilute acids or alkalls, the procedure being such that 5 to 50~ of the admixed polysaccharide derivative are washed out.
These products can he dried by means of simple conventional processes, as for example, on a fluidized bed dryer. For this purpose the particles are first freed from the excess last wash liquid by centrifuging or filtering with suction. This wash llquid should sultably be a non-aqueous or at least a partially non-aqueous medium and when required, already contains an addition of polyalkylene glycol or glycerol.
In a preferred embodiment of the process sodium carboxy-methyl cellulose having an average degree of substi-tution (DS~ of 0.4 to 1.0 is used as the polysaccharide derivatlve.
Depending on the klnd and amount of sodlum carboxy-methyl cellulose used and on the manner ln which the process ls carrled out during the aftertreatment and drylng operation more or less lntensely shrunk, substantlally lsometrlc par-tlcles are obtai.ned, These particles can absorb b.etween 1.5alld 20 ml of water per gram of dry substance. The partlcles obtained by dispersing are approxlmately spherical and have a _ 9 _ 2~7 comparatively smooth surface. The particles produced in a different manner Kave irregular shapes and rough surfaces but this does not have a detrimental effect on the important product characteristics~
The particles according to the present invention which consist of the polymer mixture can Eundamentally be dried as carefully as the pure regenerated cellulose materials.
In this case products which are less shrunk and have a high macroporosity even in the dry state are obtained. If the polysaccharide derivatives are added to the viscose solution in a dissolved form and in a concentration such that this results in a reduction of the total polymer concentration of the solution or if large amounts of the polysaccharide deri-vative are removed from the moist particles by the subsequent treatment steps, then there result, after careful drying, materials having a substantially increased pore space as com-pared with the pure regenerated cellulose products.
The application of the dressing proposed by the present invention and its production will be described by the following Examples.
Example 1 The intensely secreting wound of a patient having an Ulcus cruris was covered with an approximately 3mm layer of the dressing according to the present invention. The dressing consisted of dry spherical regenerated cellulose particles, which had been sterilized wi-th ~ rays, contained 10~ of sodium carboxy-methyl cellulose and had an average particle size of 0.2mm and a water absorption of 3.2~1 per gram. The water absorption was determined by means of the centrifugal method (Cell. Chem. Technol. 21 (1978), ~19-428 and defines the amount of water retained in the system of pores of the cellulose particles Cwater retention capacity).

The dressing was changed daily by rinsing the saturated material with normal saline solution and by applying a new dress;~ng layer of approximately 3mm thickness. After 5 days the wound had been distinctly cleaned and was almost dry.
After 9 days a conventional dressing could be applied.
Example 2 _ _ ___ A patient had an infec-ted superficial wound after a posttraumatic ostertis. The open wound was covered with an approxima-tely 3mm layer of the dressing consisting of dry granulate-like regenerated cellulose particles, which had been sterilized by irradiation with ~ rays, contained 20%
of sodium carboxy-methyl cellulose and 5~ of glycerol and had a par-ticle size of 0.1 to 0.5 mm and a water absorption of ~.6ml per gram.
The dressing was changed daily. The dressing was removed by means of a spatula. After 5 days the inflammation had subsided distinctly. The wound was evidently clean and showed healthy granulation. After eight days a conventional dressing could be applied.
Example 3 The infected, intensely oozing wound of a patient with a large-area burn was covered with an approximately 3mm layer of a dressing consisting of dry sterilized spherical regenerated cellulose particles, which had been sterilized by irradiation with ~ rays, contained 10% of sodium carboxy-methyl cellulose and 20~ of polyethylene glycol (relative molecular weight 600) and had a particle size of 0.2 to 0.3mm and a water absorption of 2.5ml per gram.
The dressing was changed daily and the saturated material was removed without damaging the bottom of the wound.
After 7 days the wound was clean and dry and the epitheliza-tion of the defect started from the edge. After 12 days the wound was ready for transplantation.
Example ~
-For producing the dressing according to the present inven-tion a mixture of 50g of viscose t8% of cellulose, 6%
of sodium hydroxide xantogenized with 35% of carbon disul-phide, relative to cellulose~ and 50g of a 4% aqueous solution of carboxy-methyl cellulose (CMCl having an average substi-tution degree of 0.3 in 150 ml of chlorobenzene containing 0.05% of oleic acid as the emulsifier was dispersed by means of a stirrer. The droplets obtained were coagulated while stirring was continued for 30 minutes at a temperature of 90 C. The resulting product of highly swollen spherical par-ticles was separated from chlorobenzene and water by filter-ing with suction. Portlons of 20g of the moist crude product obtained which had a polymer content of approximately 1.3g were applied for further processing. This procedure was also followed in some of the Examples hereafter. The particles were purified according to the following variants.
(a) The particles were washed four times, until free from alkali and salt, using lOOml of ~0% by volume aqueous methanol each time. They were then treated with 70ml of ethanol for 10 minutes.
(b) The particles were purified in process steps as follows:
lOOml of water 10 minutes 90C
lOOml of wa-ter 10 minutes 90C
lOOml of water 10 minutes room temperature 70ml of ethanol 10 minutes room temperature (c) The par-ticles were purified according to variant (b) but with the difference that the third time they were elutriated with water of 90 C.
(d) The particles were purified in process steps as follows:

lOOml of 80% by volume aqueous methanol 10 minutes room temperature lOOml of 80% by volume aqueous methanol la minutes room temperature lOOml of wa-ter lQ minutes 90 C
lOO.ml of water 10 minutes room temperature 70ml oE ethanol 10 minutes room temperature The purified spherical parti.cles were filtered with suction, dried at 105C and then had the analytical data listed in the Table hereafter:
CMC Content _ Water Absorption Soluble Matter a) 33.3% 5.9ml/g 7-4~
b) 26.4% 6.2ml/g 3.2%
c) 15.9% 7.3ml/g 1.5 d) 28.1% 7.5ml/g 1.0 Example 5 For the production of a dressing according to the present-invention spherical particles were produced analo-gously to Example 4 in several separate charges but using a CMC having a DS of Q.5 as the component of the mixture.
The spherical particles of these charges were purified accord-ing to the variant bl in Example 4 and after drying at a re-sidual solubility of 2 to 4% they had the following correl-ated values for the water absorption (within the limits of error):
Water Absorption Water Absorption Charge 16~lml~g Charge 5 6.9ml/g Charge 26~lml~g Charge 6 6.6ml/g Charge 3 5.9ml~gCharge 7 6.3ml/g Charge 4 6,5ml/~
_ ample _ ~or the production of the dressing according to the Z~7 present inventi.oll spherical particles were produced analo~o~
ly -to ~xample 4 bu-t with the use of C~qC havipg a ~S o~;0.,7,~
as -the componen-t of -the mixture and further ~reated and puri :Eied accordinc3 to various var.ian-ts~
(a) The particles were puri:Eied in process s-teps as Eollows:
100 ml of methanol 10 minutesroom temperature 100 ml of methano]. 10 minu-tesroom -tempera-ture 100 ml of water 10 minutes90C
10100 ml of wa-ter 10 minutesroom -temperature 70 ml of e-thanol 10 minutesroom temperature (b) rrhe par-ticles were purified in process s-teps as follows:
100 ml of wa-ter 10 minutes90C
100 ml of wa-ter 10 minutes90C
100 ml of wa-ter 10 minutesroom -temperature 70 ml of ethanol 10 minu-tesroom -temperature The purified and further treated particles were separa-ted from the liquid phase and dried a-t 105C. They -then showed the following values:
Water Absorption Soluble ~latter (a) 9.6 ml/g 3.4%
(b) 5.2 ml/g 2.0 Example 7 For the production of the dressing according to the present inven-tion 25g of a mixture of 12.5g of viscose ancl 12.5g of aqueous 4~ CMC (DS 0.5) were poured in-to a cylin-drical vessel having an inside diameter of approxima-tely 10 mm and -thermally coagula-ted for 90 minutes a-t 90C. The material was comminuted to a finely divided granulate having a particle size of approxima-tely 1 mm and less. The granulate was then purified according -to varian-t (a~ in Example 6. The powdery-2~7 granular product obtained after dr~ing at 105C showed awater absorption of 7.6 ml peX ~ram, Example 8 For the production o~ the dressin~ according to the present invention spherical particles were produced anal-ogously to Example 4 fiut wi-th the use of a CMC (DS 7~ partial-ly cross-linked with epichlorohydrin. The cr~c still had a solubility in water of approximately 50%. The component of the mixture was admixed with theviscose, substantially dissolved in standard solution of caustic soda. The particles obtained were purified according to the variant (d) in Example 4 and after drying at 105C they showed a water absorption of 14.0 ml per gram at a residual solubility of 0.6%.
Example 9 Corresponding to the procedure in Example 4 spheri-cal particles were produced with the addition of sodium-carboxy-methyl starch and sodium alginate. They were puri-fied according to variant (d) in Example 4 and dried at 105 C.
The product showed the following values for the water absorp-tion:

with sodium-carboxy-methyl starch: 5.7 ml/g soluble matter: 4.2%
with sodium alginate: 3.1 ml/g soluble matter: 1.5

Claims (13)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLU-SIVE PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. An absorbent dressing comprising a particulate cellulose material, the particles consisting of mixtures of regenerated cellulose and 3 to 30% of a polysaccharide deri-vative containing carboxylate groups which particles after wetting with aqueous liquids have a macroporous structure.

2. An absorbent dressing according to claim 1, in which the particles are spherical and have a diameter >10µ.

3. An absorbent dressing according to claim 1, in which the particulate material is a granulate.

4. An absorbent dressing according to claim 1, 2 or 3, which contains 5 to 90% by weight of at least one gly-cerol and polyalkylene glycol.

5. An absorbent dressing according to claim 1, 2 or 3, which absorbs wound secretions in amount of 1.5 to 20 ml per gram of dry substance including bacteria, toxins, pro-teins and inflammation mediators.

6. An absorbent dressing according to claim 1, 2 or 3, in which the polysaccharide derivative is selected from sodium-carboxy-methyl cellulose, sodium-carboxy-methyl starch and sodium alginate.

7. An absorbent dressing according to claim 1, 2 or 3, which contains 5 to 30% by weight of at least one gly-cerol and polyalkylene glycol.

8. A process for producing an absorbent dressing, in which a polysaccharide derivative containing more than 50 of water-soluble carboxylate groups in a dissolved or solid form is added to a viscose, the mixture shaped into moldings, coagulated at elevated temperature, and the particles obtain-ed are subjected to washing and dried.

9. A process according to claim 8, in which the moldings are comminuted to a particle size >10µ.

10. A process according to claim 8, in which spherical moldings haying diameters >10µ are produced by emulsifying, prior to thermal treatment, the mixture of vis-cose and polysaccharide derivative in a dispersing medium immiscible with the viscose.

11. A process according to claim 8, 9 or 10, in which the portion of polysaccharide derivative containing carboxylate groups is 5 to 50% relative to the total mass of polymer mixture in the viscose solution.

12. A process according to claim 8, 9 or 10, in which the particles obtained are subjected to a washing treat-ment with low molecular aliphatic alcohol or ketones or mixtures thereof with water and/or with water and aqueous solutions such that in said treatment a portion of 5 to 50% of the poly-saccharide present is washed out.

13. A process according to claim 8, 9 or 10, in which prior to and after the drying step at least one of glycerol and polyethylene glycol is applied to the particles in an amount such that the proportion of the substances in the final product is 5 to 30% relative to the dry polymer mass.