New polysaccharide esters are disclosed, and more precisely esters of acidic polysaccharides chosen from the group formed by carboxymethylcellulose, carboxymethyl starch and carboxymethylchitin. These new esters and some esters of the type already known are useful as medicaments, for the manufacture of pharmaceutical and cosmetic preparations, in the field of biodegradable plastic materials and, therefore, for the manufacture of medical, surgical and sanitary articles, as well as numerous other industrial sectors in the place of acidic polysaccharides now in common use.

SUMMARY 
The present invention concerns new polysaccharide esters and more precisely 
esters of acidic polysaccharides chosen from the group formed by 
carboxymethylcellulose, carboxymethylchitin and carboxymethyl starch. The 
invention also includes the use of these new esters and some esters of the 
type already known for new uses and more precisely as medicaments, for the 
manufacture of pharmaceutical and cosmetic preparations, in the sector of 
biodegradable plastic materials and, therefore, for the manufacture of 
medical, surgical and sanitary articles, in galenicals and in numerous 
industrial sectors in the place of acidic polysaccharides now in use, such 
as alginic acid, especially in the food industry. The invention also 
includes the articles resulting from these various uses. 
DETAILED DESCRIPTION OF THE INVENTION 
The esters according to the present invention include total esters and 
partial esters. In the partial esters the nonesterified carboxy groups may 
be salified with metals or organic bases. 
The carboxymethyl derivatives of the abovesaid natural polysaccharides, can 
be obtained by methods described in literature, essentially by treatment 
of the same with halo-acetic acids, such as chloroacetic acids, or their 
salts. The polysaccharides used in these preparation method and which are 
therefore the basis of the new esters of the present invention, may have a 
wide range of molecular weights, such as those of the various types of 
starch of cellulose and chitin present in natural materials. 
There are already reports in literature of "carboxymethlcellulose esters" 
prepared by alkylation of the carboxy hydroxyl with diazomethane or with 
the alcohol corresponding to the alkyl groups to be introduced in the 
presence of a strong acid. In this way partial esters are obtained which 
do not however seem to be pure esters. Thus, in the German patent No. 
957,938 carboxymethylcellulose is esterified at about 0.degree. C. with 
alcohol (methyl, propyl, butyl and octyl) and gasseous hydrochloric acid. 
In the case of methyl alcohol the reaction is effected over a period of 48 
hours, long enough for the glucoside structures present in the 
polysaccaride to be destroyed and no longer remain intact (see: 
Methanolysis of Polysaccharides; Carbohydrate Research 168 (1987) 
103-109). 
The same can be said of the products obtained according to the procedure 
described in U.S. Pat. No. 2,912,430. The preparation procedure for the 
methyl ester of carboxymethylcellulose described in LATV; PSR Zinat. Akad. 
Vestis. Kim. r. 1982/5 624-7 regards carboxymethylcellulose with 
diazomethane; this reagent is too drastic to leave intact the alcoholic 
hydroxyl groups of the polysaccharide; this ester is to be considered an 
ether ester of carboxymethylcellulose. 
Other preparations have been made of esters of bivalent alcohols of 
carboxymethylcellulose obtained by the action on the same of ethylene or 
propylene oxides (see Belgian patent No. 656,949, Japanese patents Nos. 
70.36.143 and 74.18.981). Unknown however are esters of superior bivalent 
alcohols, that is, those with 4 or more carbon atoms. 
Some esters of monovalent alcohols of carboxymethyl starch have been 
described too: thus, in the publication "Staerke" 1977, 29(4), 126-8, two 
types of carboxymethyl starch, one with low viscosity and one with high 
viscosity were benzylated with benzyl chloride in alkaline conditions at 
60.degree. and benzyl esters were obtained, in which however the 
Polysaccharide was found to be partially decarboxymethylated. 
The methyl ester of carboxymethyl starch was prepared by reacting starch 
with methylmonochloroacetate in methanol or benzene solution. The product 
proved to be esterifed to an extent of about 50% (Zesz. Nauk. Politech. 
Lodz, Che. Spozyw. 1977, 29, 5-17). No carboxymethylchitin esters have 
been described in literature. 
The esters of the carboxymethyl derivatives of the abovesaid 
polysaccharides obtained according to the abovesaid methods are always 
partial esters. Up till now it has not been possible to prepare total 
esters by such methods. Thanks to a new procedure of the present 
invention, it is now possible to have access to the total esters of the 
abovesaid carboxymethyl derivatives too. The new method consists in 
treating quaternary ammonium salts of the abovesaid acidic polysaccharides 
with an alkylating or etherifying agent in an aprotic solvent, especially 
in dimethylsulfoxide. By this method it is possible to prepare not only 
the total esters of the abovesaid monovalent or bivalent alcohols, but 
also the whole range of esters deriving too from alcohols of other series, 
such as alicyclic or heterocyclic esters, even those with quite 
complicated structures, which could not be obtainable by the prior methods 
used in the art. 
As a result, one of the main objects of the present invention is to provide 
new total or partial esters of the polysaccharides chosen from the group 
formed by carboxymethylcellulose, carboxymethyl starch and 
carboxymethylchitin with alcohols of the aliphatic, araliphatic, 
cycloaliphatic or heterocyclic series and by the salts of such partial 
esters with inorganic or organic bases, with the exception of the partial 
esters of carboxymethylcellulose with ethylene- and propyleneglycol and 
the methyl and benzyl ester of carboxymethyl starch. 
A second object of the invention is represented by a new procedure for the 
preparation of esters, of carboxymethylcellulose, carboxymethyl starch and 
carboxymethylchitin, characterized by treating a quaternary ammonium salt 
of one of these polysaccharide derivatives with an etherifying agent in an 
aprotic solvent, and, if desired, salifying in the partial esters thus 
obtained the free carboxy groups with pharmacologically acceptable 
inorganic or organic bases A third object of the invention is represented 
by the use of esters of the abovesaid derivatives of the three 
carboxymethylpolysaccharides, including the known ones, in the fields of 
medicine, pharmaceuticals and cosmetics and in the following industrial 
sectors: 
1. food industry 
2. paper industry 
3. adhesive products 
4. printing 
5. textile dyes 
6. in the preparation of sanitary, medical and surgical products 
7. in galenics for the preparation of capsules and microcapsules 
8. in biology to immobilize enzymes 
9. as emulsifyers for polishes, anti-foam agents, lactics and as 
stabilizers in the ceramic and detergent industries 
A fourth object of the invention is represented by industrial articles or 
products made with esters for the aforesaid uses and which will be 
described in more detail hereafter. 
The esters of the present invention or their salts may themselves be 
medicaments, whenever the alcohols which make up the ester group are 
therapeutically active or when the bases salifying free carboxy groups of 
partial esters are therapeutically active. In such cases the 
polysaccharide ester acts as a vehicle for such therapeutically active 
substances and medicaments in the form of such esters, possibly associated 
with other conventional excipients for pharmaceutical preparations. These 
esters have properties which are qualitatively similar to those of the 
therapeutically active alcohol used as the esterifying agent, or similar 
to that of the therapeutically active base used as the salifying component 
or of both these categories of substances. However, the new esters of the 
invention have a more differentiated range of action, even with regard to 
the known esters, ensuring a more balanced, constant and regular 
pharmacological action and usually achieving a marked retard effect. 
One particular case of such medicaments is represented by esters in which 
one part of the carboxy groups is esterified with therapeutically active 
alcohols and another part with pharmacologically indifferent alcohols, or 
whose activity is negligible. By suitably dosing the percentages of the 
two types of alcohol as esterifying component, it is possible to obtain 
esters with the same activity as the pharmacologically active alcohol and 
in which the abovesaid properties of increased bioavailability and 
stability are made full use of. Lastly, it is possible to prepare 
mixed-type esters in which the ester groups derive from two different 
therapeutically active alcohols, for example from a cortisone steroid and 
from an antibiotic, while other carboxy groups may be free or salified, 
for example, with alkaline metals, especially with sodium. 
It is however also possible to prepare esters with three or more alcohol 
components, for example esters in which part of the carboxy groups are 
esterifed with a therapeutically active alcohol, another part with another 
therapeutically active alcohol, a third part with a therapeutically 
inactive alcohol and a fourth part is possibly salified with a metal or 
with a therapeutically active or inactive base, or it is in free form. 
The vehicling of therapeutically active substances, apart from the 
esterification of therapeutically active alcohols, can also be achieved by 
the simple association of an ester of the type of the present invention 
(new or known) with the therapeutically active substance, that is, in a 
physical mixture. ln this case it is preferable to use carboxymethyl 
esters derived from cellulose starch and chitin esters with 
therapeutically indifferent alcohols, and the therapeutically active 
substance may be for example of an acidic or neutral character. If the 
esters of the carboxymethyl polysaccharide derivatives are partial, the 
free carboxy groups may be salified with inorganic or organic bases. By 
using therapeutically active bases for the salification, it is possible to 
obtain stechiometrically neutral salts or acid salts or basic salts 
according to the quantity of base used for the salification and the use of 
these salts therefore constitutes another way of vehicling the medicaments 
through the esters of the present invention. Regarding the vehicling 
action of the new esters and also of those already known (since this 
property has never been described in literature) it is possible therefore 
to prepare new medicaments including: 
1. a pharmacologically active substance or an association of two or more 
such substances; and 
2. a total or partial ester of a carboxymethyl derivative of cellulose, 
starch, or chitin or one of its salts and such medicaments are a further 
object of the invention. 
The esters to be used in these medicaments are above all those in which the 
esterifying alcohol is itself not pharmacologically active, for example a 
simple aliphatic alcohol, such as one of those named hereafter. The 
invention does not however exclude medicaments of this type in which the 
ester too is pharmacologically active, such being the case for example of 
one of the abovesaid esters deriving from pharmacologically active 
alcohols. 
In such medicaments, where partial esters are used, possible salification 
of the remaining carboxy groups is carried out preferably with 
therapeutically neutral inorganic or organic bases, especially with 
alkaline metals, such as sodium or ammonium. Should the active substance 
1) or a corresponding association of substances have basic groups, such as 
for example antibiotics containing amino groups, and should partial esters 
of acidic carboxymethyl-polysaccharide acid be used with remaining free 
carboxy groups, the corresponding salts are formed between these and the 
basic substances. The basic substance may of course be in excess, 
producing basic salts, or in an amount less than that needed to salify all 
carboxy groups, producing acid salts. The new medicaments therefore 
include in particular the partial esters of carboxymethyl-polysaccharide 
acid partially salified with pharmacologically active substances of a 
basic character, as described above. The nonesterified carboxy groups may 
themselves be salified with therapeutically active bases, even where the 
vehicled substance is not of a basic nature. 
Carboxymethyl-polysaccharide esters are particularly useful as vehicles in 
ophthalmology, where a particular compatibility is to be noted between the 
new products and the corneal epithelium, and therefore excellent 
tolerability with no sensitization effects. 
Furthermore, when the medicaments are administered in the form of 
concentrated solutions with elastic, viscous characteristics or in solid 
form, it is Possible to obtain homogenous, stable, perfectly transparent 
and adhesive films on the corneal epithelium which also guarantee 
prolonged bioavailability of the drug and which represent excellent retard 
effect preparations. Such ophthalmic medicaments are exceptionally 
valuable in the veterinary field, considering that there are at present no 
veterinary preparations containing chemotherapeutic substances for use in 
the eyes. Indeed, preparations for human use are normally used for animals 
too, and these do not always guarantee a specific range of action or they 
do not always allow for the particular conditions under which treatment 
must take place. This is the case, for example of therapy for infections 
keratoconjuntivitis, pink eye or IBK, an infection which mainly affects 
cattle, sheep and goats. Presumably these three species have specific 
etiologic factors and more particularly: in cattle the main microorganism 
involved would appear to be Moraxella bovis (even though it is not 
possible to exclude other agents of a viral origin, such as 
Rhinotracheitis virus, in sheep Micoplasma, Rickettsiae and Clamidiae, in 
goats Rickettsiae). 
The disease manifests itself in acute form and tends to spread rapidly: in 
the initial stages the symptoms are characterized by blepharospasm and 
excessive lacrimation, followed by purulent exudate, conjunctivitis and 
keratitis, often associated with high temperature, reduced appetite and 
milk production. Particularly serious are the corneal lesions which in the 
final stages may even cause Perforation of the cornea itself. The clinical 
course of the disease varies from a few days to several weeks. A vast 
range of chemotherapeutic agents are used in treatment, administered both 
topically (often associated with steroid antiinflammatory agents), and 
systemically, and among these are: tetracyclines, such as oxytetracycline, 
penicillins, such as cloxacillin and benzylpenicillin, sulfamides, 
polymixin B (associated with miconazole and prednisolone), chloramphenicol 
and tylosin. Topical treatment of the disease, despite its apparent 
simplicity, is still open to debate, since the ocular preparations used to 
date do not, for one reason or another, allow therapeutically efficacious 
concentrations of antibiotic or sulfamide to be obtained in the tears. 
This is understandable in the case of solutions, considering the 
predominantly tilted position of the head in the above animals, but it is 
also true of the semisolid medicaments, as the excipients normally used in 
the same do not adhere sufficiently to the surface of the cornea, since 
they do not generally have a high enough concentration of active substance 
and are impossible to satisfactorily distribute over the surface to be 
treated (presence of a distribution gradient). 
These drawbacks to conventional eye drops used in ophthalmology have been 
described by Slatter et al. in "Austr. vet. J.," 1982, 59 (3), pp. 69-72. 
With the esters of the present invention these difficulties can be 
overcome. The presence of carboxymethyl-polysaccharide ester as vehicle 
for ophthalmic drugs does indeed allow the formulation of excellent 
preparations free from concentration gradients of the active substance and 
therefore perfectly homogenous, perfectly transparent and perfectly 
adhesive to the corneal epithelium, free from sensitization effects and 
with the active substance contained in an excellent vehicle and possibly 
with a retard effect. 
The above properties of the new medicaments can of course also be put to 
use in other fields besides ophthalmology: they can be applied in 
dermatology and in infections of the mucus, for example of the mouth. 
They can also be used to obtain a systemic effect thanks to transcutaneous 
absorption, for example in suppositories. All these applications are 
feasible both in human and veterinary medicine. In human medicine the new 
medicaments are particularly suitable for use in pediatrics. The present 
invention therefore also includes in particular any one of these 
therapeutic applications. 
For the sake of brevity, reference hereinafter to the active substance of 
component 1) according to the invention should be understood to encompass 
the presence of a single active substance and also the association or 
mixture of two or more active substances 
Component 1) defined above may first and foremost be enumerated according 
to its use in various fields of therapy, beginning with the distinction 
between human and veterinary medicine and then specifying the various 
sectors of application with regards to the organs or tissues to be 
treated, such as ophthalmology, dermatology, otorhinolaryngology, 
gynaecology, angiology, neurology or any other type of pathology of the 
internal organs which can be treated by topical applications, such as 
rectal applications. According to one particular aspect of the present 
invention, the pharmacologically active substance 1) is first and foremost 
a substance for ophthalmic use. On the basis of another criterion the 
pharmacologically active substance 1) should be distinguished with regard 
to its effect and may therefore, for example, be in the form of an 
anesthetic, analgesic, antiinflammatory drug, a vasoconstrictor, 
antibacterial, or antiviral. For the ophthalmic sector it can be indicated 
particularly and for example for its: miotic, antiinflammatory, wound 
healing and antimicrobial effects. Component 1) may also be, according to 
the invention, an association of two or more active substances, as 
contained in many known medicaments. For example, in ophthalmology, they 
may be associated with an antibiotic, an antiphlogistic and a 
vasoconstrictor or with several antibiotics one or more antiphlogistics, 
or with one or more antibiotics, a mydiatric or miotic or wound healing 
agent or an antiallergic etc. For example the following associations of 
ophthalmic drugs may be used: kanamycin+phenylephrine+dexamethasone 
phosphate, kanamycin+betamethasone phosphate +phenylephrine, or similar 
associations with other antibiotics used in ophthalmology, such as 
rolitetracycline, neomycin, gentamycin, tetracyline. In dermatology it is 
possible to have as active component 1) associations of various 
antibiotics, such as erythromycin, gentamycin, neomycin, gramicidin, 
polymyxin B, between themselves, or of the same antibiotics with 
antiinflammatory agents, for example corticosteroids, for example 
hydrocortisone+neomycin, hydrocortisone+neomycin+polymyxin B+gramicidin, 
dexamethasone+neomycin, fluorometholone +neomycin, prednisolone+neomycin, 
triamcinolone+neomycin+gramicidin+nystatin, or any other association used 
in conventional dermatological preparations. Associations of different 
active substances are not of course limited to this field, but in each of 
the abovesaid fields of medicine it is possible to use associations 
similar to those already in use for the pharmaceutical preparations known 
to the art. 
In the case referred to above of the use of a basic-type substance 1), the 
salts which are formed with a partial carboxymethyl-polysaccharide ester 
may be of various types, and that is, the remaining carboxy groups may be 
salified, or only an aliquot part, thus obtaining acid salts--esters, or 
neutral salts--esters. The number of acidic groups to be kept free may be 
important for the preparation of medicaments with a particular pH. 
According to one particular aspect of the invention it is possible to 
prepare medicaments of this type starting from previously isolated and 
possibly purified salts, in an anhydrous solid state, as amorphous powders 
which on contact with the tissue to be treated constitute a concentrated 
aqueous solution of a gelatinous character, viscous in consistency and 
with elastic properties. These qualities are maintained even at higher 
dilutions and it is therefore possible to use, instead of the abovesaid 
anhydrous salts, more or less concentrated solutions in water or in 
physiological solution, possibly with the addition of other excipients or 
additives, such as other mineral salts to regulate the pH and the osmotic 
pressure It is of course also possible to use salts to make gels, inserts, 
creams or ointments, containing other excipients or ingredients used in 
traditional formulations of these pharmaceutical preparations. 
According to one preferential aspect of the invention however, medicaments 
containing the carboxymethylpolysaccharide ester or its salts are used 
alone as the vehicle with therapeutically active or inactive substances 
(apart from possibly aqueous solvent). Also included in the invention are 
those mixtures obtainable for all the types of medicament described here 
and also mixtures of such medicaments, such as possibly also mixtures of 
carboxymethyl-polysaccharide esters with the corresponding free acid 
groups or mixtures of their salts, for example sodium salts. 
Examples of pharmacologically active substances 1) to be used in ophthalmic 
medicaments according to the invention are: basic or nonbasic antibiotics, 
for example aminoglycosides, macrolides, tetracyclines and peptides, for 
example gentamycin, neomycin, streptomycin, dihydrostreptomycin, 
kanamycin, amikacin, tobramycin, spectinomycin, erythromycin, 
oleandomycin, carbomycin, spiramycin, oxytetracycline, rolitetracycline, 
bacitracin, Polymyxin B, gramicidin, colistin, chloramphenicol, 
lincomycin, vancomycin, novobiocin, ristocetin, clindamycin, amphotericin 
B, griseofulvin, nystatin and possibly their salts, such as sulfates or 
nitrates, or associations between themselves or with other active 
principles, for example those named hereafter. 
Other ophthalmic drugs to be used to advantage according to the present 
invention are: other antiinfectious agents such as diethylcarbamazine, 
mebendazole, sulfamidics such as sulfacetamide, sulfadiazine, 
sulfisoxazole; antivirals and antitumorals such as iododeoxyuridine, 
adenine arabinoside, trifluorothymidine, acyclovir, ethyldeoxyuridine, 
bromovinyldeoxyuridine, 5-iodo-5'-amino-2',5'-dideoxyuridine; steroid 
antiinflammatories, for example dexamethasone, hydrocortisone, 
prednisolone, fluorometholone, medrisone and possibly their esters, for 
example phosphoric acid esters; nonsteroid antiinflammatory agents, for 
example indomethacin, oxyphenbutazone, flurbiprofen; wound healers such as 
the epidermal growth factor EGF; local anesthetics, such as Benoxinate, 
proparacain and possibly their salts; cholinergic agonist drugs such as 
pilocarpine, methacholine, carbamylcholine, aceclidine, physostigmine, 
neostigmine, demecarium and possibly their salts; cholinergic antagonist 
drugs such as atropine and its salts; adrenergic agonist drugs such as 
noradrenalin, adrenalin, naphazoline, methoxamine and possibly their 
salts; adrenergic blockers such as propanolol, timolol, pindolol, 
bupranolol, atenolol, metoprolol, oxprenolol, practolol, butoxamine, 
sotalol, butedrin, labetalol and possibly their salts. 
Also, associations of such drugs between themselves and possibly with other 
principles may be used as component 1) according to the invention. If, in 
the place of one single active substance 1), associations of active 
substances are used, such as those named above, the salts between the 
basic active substances and the partial carboxymethylpolysaccharide ester 
may be mixed salts of one or more of such basic substances or possibly 
mixed salts of this type with a certain number of further acid groups of 
the polysaccharide salified with the aforesaid bases or metals. For 
example it is possible to prepare salts of a partial ester of 
carboxymethylpolysaccharide acid with a pharmacologically inactive 
alcohol, for example an inferior alkanol and with a certain percentage of 
acid groups salified with the antibiotic kanamycin, another percentage 
salified with the vasoconstrictor phenylephrine, there then being possibly 
a remaining percentage of acid groups free or salified for example with 
sodium or one of the other abovesaid metals. 
Examples of active substances to be used alone or in associations between 
themselves or with other active principles in dermatology are: therapeutic 
agents such as anti-infectious agents, antibiotics, antimicrobials, 
antiinflammatories, cytostatics, cytotoxics, antivirals, anesthetics, and 
preventive agents, such as sun shields, deodorants, antiseptics and 
disinfectants. Among the antibiotics are erythromycin, bacitracin, 
gentamycin, neomycin, aureomycin, gramicidin and associations of the same, 
the antibacterials and disinfectants include nitrofurazone, mafenide, 
clorexidine, and derivatives of 8-hydroxychinoleine and possibly their 
salts; the antiinflammatories include above all corticosteroids such as 
prednisolone, dexamethasone, fIumethasone, clobetasol, acetonide of 
triamcinolone, betamethasone or their esters, as valerianates, benzoates, 
dipropionates; as cytotoxics fluorouracil, methotrexate, podophyllin; 
among the anesthetics are dibucaine, lidocaine, benzocaine. 
The items in this list are of course only examples and any other agent 
described in literature may be used. 
From the examples given for ophthalmology and dermatology it is possible to 
deduce which medicaments according to the present invention are to be used 
in the above fields of medicine, for example in otorhinolaryngology or 
odontology or in internal medicine, for example in endocrinology, where it 
is possible to use preparations for intradermal absorption or through the 
mucus, for example rectal or intranasal absorption, for example as nasal 
sprays or for inhalation into the oral cavity or into the pharynx. 
Such preparations may therefore be for example antiinflammatories, or 
vasoconstrictors or vasopressors such as those named for ophthalmology, 
vitamines, antibiotics, such as those named above, hormones, 
chemotherapeutic agents, antibacterials, etc. also as named above for use 
in dermatology 
The medicaments according to the invention may be in solid form, for 
example as freeze-dried powders containing only the two components mixed 
together or prepared separately. 
Such medicaments in solid form, on contact with the epithelium to be 
treated, more or less concentrated solutions according to the nature of 
the particular epithelium, with the same characteristics as the solutions 
previously prepared in vitro and which represent another particularly 
important aspect of the present invention. Such solutions are preferably 
in distilled water or in sterile physiological solutions and contain 
preferably no other pharmaceutical vehicle other than 
carboxymethylpolysaccharide ester or one of its salts. Concentrations of 
such solutions may also vary within a wide range, for example between 0.01 
and 75% both for each of the two separate components and for their 
mixtures or salts. Particular preference is given to solutions with a 
marked elastic, viscous character, for example with a content of between 
10% and 90% of the medicament or of each of its two components. 
Particularly important are medicaments of this type, both in an anhydrous 
form (freeze-dried powders) or as solutions, either concentrated or 
diluted in water or saline, possibly with the addition of additive or 
auxiliary substances, such as in particular disinfectant substances or 
mineral salts acting as buffer or others, for ophthalmic use. 
Among the medicaments of the invention the ones to be chosen in each case, 
are the ones with a degree of acidity suitable for the environment to 
which they are to be applied, that is, with a physiologically tolerable 
pH. Adjustment of the pH, for example in the abovesaid salts of the 
partial ester with a basic active substance, can be done by suitably 
regulating the quantity of polysaccharide, of its salts and of the basic 
substance itself. Thus, for example, if the acidity of a salt of the 
partial ester with a basic substance is too high, the excess of free acid 
groups is neutralized with the abovesaid inorganic bases, for example with 
sodium, potassium or ammonium hydrate. 
The pharmaceutical preparations containing therapeutically active 
carboxymethylpolysaccharide esters, possibly in the form of the abovesaid 
medicaments resulting from the association of components 1) and 2), 
contain common excipients and may be used for oral, rectal, parenteral, 
subcutaneous, local or intradermal use. They are therefore in solid or 
semisolid form, for example pills, tablets, gelatinous capsules, capsules, 
suppositories, soft gelatin capsules. For parenteral and subcutaneous use 
it is possible to use forms intended for intramuscular or intradermal use, 
or suitable for infusions or intravenous injections and can therefore be 
presented as solutions of the active compounds or as freeze-dried powders 
of the active compounds to be mixed with one or more pharmaceutically 
acceptable excipients or diluents, suitable for the abovesaid uses and 
whose osmolarity is compatible with the physiological fluids. For local 
use, preparations in the form of sprays come into consideration, for 
example nasal sprays, creams or ointments for topical use or sticking 
plasters specially prepared for intradermal administration. The 
preparations of the invention may be used for administration to man or 
animals. They contain preferably between 0.01% and 10% of active component 
per solutions, sprays, ointments and creams and between 1% and 100% and 
preferably between 5% and 50% of active compound for the preparations in 
solid form. The dosage to be administered depends on specific indications, 
on the desired effect and on the chosen administration route. Daily doses 
of such preparations can be deduced by considering that used for the 
corresponding known preparations for corresponding cures of the 
therapeutically active alcohol whose action is to be exploited. Thus, for 
example, dosage of a carboxymethylchitin ester with cortisone can be 
derived from its content of this steroid and from its usual dosage in the 
known pharmaceutical preparations. 
One particular form of pharmaceutical preparations is represented by the 
abovesaid medicaments constituted by the association of a 
carboxymethylpolysaccharide ester by an active substance, for example for 
topical use. These may also be in solid form, for example as freeze-dried 
powders containing only the two components 1) and 2) in a mixture or 
packed separately. Such medicaments in solid form, on contact with the 
epithelium to be treated, create more or less concentrated solutions 
according to the nature of the particular epithelium with the same 
characteristics as the solutions previously prepared in vitro and which 
represent another particularly important aspect of the present invention. 
Such solutions are preferably in distilled water or in sterile 
physiological solutions and contain preferably no other pharmaceutical 
vehicle other than the ester of carboxymethylpolysaccharide or one of its 
salts Concentrations of such solutions may also vary within a wide range, 
for example between 0.01 and 75% both for each of the two separate 
components and for their mixtures or salts. Particular preference is give 
to solutions with a marked elastic, viscous character, for example with a 
content of between 10% and 90% of the medicament or of each of its two 
components 
Particularly important are medicaments of this type, both in an anhydrous 
form (freeze-dried powders) or as concentrated solutions or diluted in 
water or saline, possibly with the addition of additive or auxiliary 
substances, such as in particular disinfectant substances or mineral salts 
acting as buffer or others, for ophthalmic use. 
Among the medicaments of the invention, the ones to be chosen in each case, 
are the ones with a degree of acidity suitable for the environment to 
which they are to be applied, that is, with a physiologically tolerable 
pH. Adjustment of the pH, for example in the abovesaid salts of 
carboxymethylpolysaccharide esters with a basic active substance, can be 
done by suitably regulating the quantity of polysaccharide, of its salts 
and of the basic substance itself. Thus, for example, if the acidity of a 
salt of a carboxymethylpolysaccharide ester with a basic substance is too 
high, it is neutralized with the excess of free acid groups with the 
abovesaid inorganic bases, for example with sodium, potassium or ammonium 
hydrate. 
In the cosmetic articles according to the invention, the esters of 
carboxymethylpolysaccharides and their salts are mixed with excipients 
commonly used in the art and are for example those already listed above 
for pharmaceutical preparations. Above all are used creams, ointments, 
lotions for topical use in which the carboxymethylpolysaccharide ester or 
one of its salts may constitute the cosmetic active principle possibly 
with the addition of other cosmetically active principles, such as for 
example steroids, for example pregnenolone, or one of the principles 
reported above. In such preparations the polysaccharide ester may be an 
ester with a cosmetically active alcohol, such as dexpantenol, or also an 
ester with a cosmetically inactive alcohol, such as inferior aliphatic 
alcohol, for example one of those named. The effect is due to the 
intrinsic cosmetic properties of the polysaccharide component. The 
cosmetic articles can however be based on various other active principles, 
for example disinfectant substances or sunshields or waterproofing agents 
or regenerating or antiwrinkle substances, or odoriferous substances, 
especially perfumes. In this case the polysaccharide ester may itself be 
the active ingredient and derive from alcohols which have such properties, 
for example from superior aliphatic alcohols or terpene alcohols in the 
case of perfumes or may function above all as a vehicle for substances 
with such properties as are associated with them. Particularly important 
are therefore cosmetic compositions similar to the medicaments described 
above in which the pharmaceutically active component 1) is substituted by 
a cosmetological factor, and the respective salts. Use of the abovesaid 
esters deriving from alcohols used in the perfume industry represents a 
big step forward in technique, since it allows for slow, constant and 
prolonged release of the odorous principles. 
An important application of the present invention concerns sanitary and 
surgical articles, the methods for their manufacture and their use. The 
invention therefore embraces all articles similar to those already on the 
market but containing an ester of carboxymethyl-cellulose, starch or 
-chitin, for example inserts or ophthalmic lenses. 
Absolutely new surgical and sanitary articles according to the present 
invention are represented by esters of carboxymethyl-polysaccharide acid 
regenerated as such by appropriate organic solutions, suitable to be made 
into sheet or thread form, obtaining films, sheets and threads for use in 
surgery, as auxiliaries and skin substitutes in severe cases of damage to 
this organ, such as for example following burns, or as suture threads in 
surgical operations. The invention includes in particular these uses and a 
procedure for the preparation of such articles consisting of (a) forming a 
solution of polysaccharide ester or of one of its salts in a suitable 
organic solvent, for example a ketone, an ester or an aprotic solvent such 
as an amide of a carboxy acid, especially a dialkylamide or of an 
aliphatic acid with between 1 and 5 carbon atoms and deriving from alkyl 
groups with between 1 and 6 carbon atoms, and especially from an organic 
sulfoxide, that is a dialkylsulfoxide with alkyl groups with a maximum of 
6 diethylsulfoxide and also especially a fluorurate solvent with a low 
boiling point, such as especially hexafluoro-isopropanol, (b) working this 
solution sheet or thread form and (c) removing the organic solvent by 
contact with another organic or aqueous solvent which will mix with the 
first solvent and in which the polysaccharide ester is insoluble, 
especially an inferior aliphatic alcohol, for example ethyl alcohol (Wet 
spinning), or, should a solvent with a not too high boiling point be used 
to prepare the solution of the polysaccharide derivative, (d) removing 
this solvent in dry conditions with a current of gas, especially suitably 
heated nitrogen (Dry spinning). Dry-wet spinning can also be used to great 
effect 
The threads obtained with the esters of carboxymethyl-polysaccharide acids 
may be used to prepare lints for use in the medication of injuries and in 
surgery. These lints have the extraordinary advantage of being 
biodegradable in the organism, thanks to the enzymes they contain. Such 
enzymes split the ester into carboxymethyl-polysaccharide acid and the 
corresponding alcohol, should an ester deriving from a therapeutically 
acceptable alcohol be used, such as ethyl alcohol. 
Preparation of the abovesaid sanitary and surgical articles can include the 
addition of plastifying materials to improve their mechanical 
characteristics, such as in the case of threads, to improve their 
resistance to tangles. These plastifying materials may be for example 
alkaline salts of fatty acids, for example stearate of sodium or palmitate 
of sodium, the esters of organic acids with a high number of carbon atoms, 
etc. Another application of the new esters where their biodegradability is 
taken advantage of by the esterases present in the organism, is 
represented by the preparation of capsules for subcutaneous implantation 
of medicaments or microcapsules to be administered by injection, for 
example by subcutaneous or intramuscular route. 
Of great importance is also the preparation of microcapsules containing the 
new esters, a problem-free method for their use, which up till now has 
been very limited, for the reasons explained above, and which opens up a 
whole new area of application where a retard effect is to be achieved by 
injection. 
Another application in the medical and surgical sectors of the new esters 
lies in the preparation of a wide variety of solid inserts such as plates, 
discs, sheets, etc replacing the metal or synthetic plastic ones currently 
in use, in cases calling for temporary inserts to be removed after a 
certain length of time. Preparations containing animal collagen, being of 
a proteic nature, often give rise to unpleasant side effects, such as 
inflammation or rejection. In the case of the esters of the present 
invention, this danger is overcome. 
Another application in the fields of medicine and surgery of the new esters 
according to the present invention is represented by preparations in 
expandable material, especially in the form of sponges, for the medication 
of injuries or various types of lesion. 
The esterified carboxymethyl-polysaccharides of the present invention are 
extremely suitable, thanks to their viscosity in aqueous solutions, for 
the preparation of gels which can be widely used in the food industry, for 
example for the manufacture of ice creams, puddings and many other types 
of sweet dishes. They can also be used, thanks to their water retaining 
properties, for the conservation of frozen foods. Another property of the 
esters of carboxymethylderivatives of the above polysaccharides is their 
ability for form and to stabilize emulsions and they can therefore also 
serve in the food industry for the preparation of seasonings and for the 
stabilization of many drinks such as beer or fruit juices, sauces and 
syrups. 
The ease with which the esters of the present invention form films and 
threads can be put to good use in the paper industry, for the manufacture 
of stickers or adhesive labels, in printing and in textile dyeing As 
emulsifiers they can be used for the manufacture of polishes, anti-foam 
agents, lactics and as stabilizers in the ceramics and detergent 
industries. 
Use of the new esters according to the present invention (or also of 
previously known esters of this type) in the food industry presents 
various advantages over the polysaccharides usually used in the industry, 
for example alginic acid which has a tendency to precipitate in acid 
conditions. In the presence of calcium ions too the insoluble products 
constituted by calcium alginate may become separated, and for this reason 
the use of alkaline alginates is compromised whenever they are intended 
for use in liquids containing the abovesaid ions, for example in products 
containing milk or its derivatives. For this reason alkaline alginates 
were substituted by glycol esters of alginic acid, particularly 
propyleneglycol ester. Glycol esters may however be toxic to a certain 
degree and their use must therefore be kept within certain limits. These 
drawbacks do not exist for example in the case of the esters of monovalent 
alcohols of the present invention, which can be used preferably for the 
preparation of the abovesaid food additives. 
Also regarding the other abovesaid uses, the new polysaccharide esters open 
up a choice of surrogates which are an improvement on the products already 
in use. From the following list of alcohols, which can be used as 
esterifying components for carboxymethylpolysaccharides which are the 
basis of the present invention, those suitable for the use in question 
should be chosen. Thus for example for all uses 1)-9) in the abovesaid 
sectors of industry alcohols of the aliphatic series with a low or medium 
number of carbon atoms should be preferred, or also simple heterocyclic 
alcohols or araliphatic alcohols. The cycloaliphatic alcohols, in 
particular terpene alcohols should be used preferably for cosmetic 
products. As for the alcohols for use in the medicaments or pharmaceutical 
preparations described above, they are those to be considered as 
therapeutically active esterifying components, for example steroid or 
vitamin alcohols. 
Alcohols of the aliphatic series to be used as esterifying components of 
the carboxy groups of carboxymethyl derivatives according to the various 
aspects of the present invention are for example those with a maximal of 
34 carbon atoms, which may be saturated or unsaturated and which may 
possibly also be substituted by other free functional or functionally 
modified groups, such as amino, hydroxy, aldehydo, keto, mercapto, carboxy 
groups or by groups derived from these, such as hydrocarbyl or 
dihydrocarbylamino groups (hereafter the term "hydrocarbyl" should be 
taken to mean not only monovalent radicals of hydrocarbons for example of 
the C.sub.n H.sub.2 n+1 type, but also bivalent or trivalent 
"alkylidenes"=C.sub.n H.sub.2n), ether or ester groups, acetal or ketal 
groups, thioether or thioester groups, and esterified carboxy groups or 
carbamidic groups perhaps substituted by one or two hydrocarbyl groups, by 
nitrile groups or by halogens. 
In the abovesaid groups containing hydrocarbyl radicals these are 
preferably inferior aliphatic radicals, for example alkyls, with a maximum 
of 6 carbon atoms. Such alcohols may also be interrupted in the carbon 
atom chain by heteroatoms, such as oxygen, nitrogen and sulfur atoms. 
It is preferable to choose alcohols substituted with one or two of the 
abovesaid functional groups Alcohols of the abovesaid group to be used 
preferably within the scope of the present invention are those with a 
maximum of 12 and especially 6 carbon atoms and in which the hydrocarbyl 
radicals in the abovesaid amino, ether, ester, thioether, thioester, 
aceto, ketal groups represent alkyl groups with a maximum of 4 carbon 
atoms, and also in the esterified carboxy or substituted carbamidic groups 
the hydrocarbyl groups are alkyls with the same number of carbon atoms, 
and in which the amino or carbamidic groups may be alkylene amino or 
alkylene carbamidic groups with a maximum of 8 carbon atoms. Of these 
alcohols, special mention should be made of those which are saturated and 
unsubstituted such as for example methyl, ethyl, propyl, isopropyl 
alcohols, n-butyl, isobutyl, tertbutyl alcohols, amyl alcohols, pentyl, 
hexyl, octyl, nonyl and dodecyl alcohols and above all those with a linear 
chain, such as n-octyl alcohol or n-dodecyl alcohol. Among the substituted 
alcohols of this group are bivalent alcohols such as ethylene glycol, 
popylene glycol or butylene glycol, trivalent alcohols such as glycerin, 
aldehydo-alcohols such as tartronic alcohol, carboxy alcohols such as 
lactic acid, for example .alpha.-oxypropionic acid, glycolic acid, malic 
acid, tartaric acids, citric acid, aminoalcohols, such as aminoethanol, 
aminopropanol, n-aminobutanol and their dimethylated and diethylated 
derivatives in the amino function, choline, pyrrolidinylethanol, 
piperidinylethanol, piperazinylethanol and the corresponding derivatives 
of n-propyl n-butyl alcohols, monothioethylenglycol and its alkyl 
derivatives, for example the ethylate derivative in the mercapto function. 
Among the saturated superior aliphatic alcohols are for example cetyl 
alcohol and myricyl alcohol, but especially important for the aims of the 
present invention are unsaturated superior alcohols with one or two double 
bonds, such as especially those contained in many essential oils and 
having affinity with terpenes, for example citronellol, geraniol, nerol, 
nerolidol, linalool, farnesol, phytol. Of the inferior unsaturated 
alcohols, allyl alcohol and propargyl alcohol should be considered. Of the 
araliphatic alcohols, special mention should be made of those with one 
single benzene residue and in which the aliphatic chain has a maximum of 4 
carbon atoms and in which the benzene residue may be substituted by 
between 1 and 3 methyl or hydroxy groups or by halogen atoms, especially 
by chlorine, bromine, iodine, and in which the aliphatic chain may be 
substituted by one or more functions chosen from the group constituted by 
free or mono or dimethylated amino groups or by pyrrolidine or piperidine 
groups. Of such alcohols special mention should be made of benzyl alcohol 
and phenethyl alcohol. 
Alcohols of the cycloaliphatic or aliphatic cycloaliphatic series may 
derive from mono or polycyclic hydrocarbons and may have a maximum of 34 
carbon atoms. Among the alcohols derived from single-ringed cyclic 
hydrocarbons, special mention should be made of those with a maximum of 12 
carbon atoms, the rings having preferably between 5 and 7 carbon atoms, 
which may be substituted for example by between one and three inferior 
alkyl groups, such as methyl, ethyl, propyl or isopropyl groups. As 
specific alcohols of this group we can mention cyclohexanol, 
cyclohexanediol, 1,2,3-cyclohexanetriol and 1,3,5-cyclohexanetriol 
(phloroglucitol), inositol, and then the alcohols which derive from 
p-menthane, such as carvomenthol, menthol, and .alpha. and 
.gamma.-terpineol, 1-terpineol, 4-terpineol and piperitol, or the mixture 
of these alcohols known as "terpineol", 1,4-and 1,8-terpin Of the alcohols 
deriving from hydrocarbons with condensed rings, for example those of the 
group including thujane, pinane or camphane, we can mention thujanol, 
sabinol, pinol hydrate, D and L-borneol and D and L-isoborneol. 
Polycyclic cycloaliphatic aliphatic alcohols to be used for the esters of 
the present invention are sterols, cholic acids and steroids, such as 
sexual hormones and their synthetic analogues and particularly 
corticosteroids and their derivatives Thus for example the following can 
be used: cholesterol, dihydrocholesterol, epidihydrocholesterol, 
corpostanol, epicoprostanol, sitosterol, stigmasterol, ergosterol, cholic 
acid, deoxycholic acid, lithocholic acid, estriol, estradiol, equilenin, 
equilin and their alkyl derivatives, as well as their ethynyl and propynyl 
derivatives in position 17, for example 17 .alpha.-ethynyl-estradiol or 
7-.alpha.-methyl-17-.alpha.-ethynylestradiol, pregnenolone, pregnandiol, 
testosterone and its derivatives, such as 17-.alpha.-methyltestosterone, 
1,2-dehydrotestosterone and 17-.alpha.-methyl-1,2-dehydrotestosterone, 
alkynyl derivatives in position 17 of testosterone and 
1,2-dehydrotestosterone, such as 17-.alpha.-ethynyltestosterone, 
17-.alpha.-propynyltestosterone, norgestrel, hydroxyprogesterone, 
corticosterone, deoxycorticosterone, 19-nortestosterone, 
19-nor-17-.alpha.-methyltestosterone and 
19-nor-17-.alpha.-ethynyltestosterone, cortisone, hydrocortisone, 
prednisone, prednisolone, fludrocortisone, dexamethasone, betamethasone, 
paramethasone, flumethasone, fluocinolone, fluprednylidene, clobetasol, 
beclomethasone, aldosterone, deoxycorticosterone, alfaxalone, alfadolone, 
bolasterone and antihormones such as cyproterone. 
Useful esterifying components for the esters of the present invention are 
genins (aglycons) of cardioactive glycosides, such as digitoxigenin, 
gitoxygenin, digoxygenin, strophanthidin, tigogenin and saponins. 
Other alcohols for use according to the invention are vitamin alcohols, 
such as axerophthol, vitamins D.sub.2 and D.sub.3, aneurine, lactoflavine, 
ascorbic acid, riboflavine, thiamine, pantothenic acid Heterocyclic 
alcohols to be used are for example are furfuryl alcohol, alkaloids and 
derivatives such as atropine, scopolamine, cinchonine, cinchonidine, 
quinine, morphine, codeine, nalorphine, N-butylscopolammonium bromide, 
ajmaline; phenylethylamines such as ephedrine, isoproterenol, epinephrine; 
phenothiazine drugs such as perphenazine, pipothiazine, carphenazine, 
homophenazine, acetophenazine, fluphenazine, N-hydroxyethylpromethazine 
chloride; thioxanthene drugs such as flupenthixol and clopenthixol; 
anticonvulsivants such as meprophendiol, antipsychotics such as opipramol; 
antiemetics such as oxypendyl; analgesics such as carbetidine and 
phenoperidine and methadol; hypnotics such as etodroxizine; anorexics such 
as benzhydrol and diphemethoxidine; minor tranquilizers such as 
hydroxyzine; muscle relaxants such as cinnamedrine, diphylline, 
mephenesin, methocarbamol, chlorphenesin, 2,2-diethyl-1,3-propanediol, 
guaifenesin, idrocilamide; coronary vasodialtors such as dipyridamole and 
oxyfedrine; adrenergic blockers such as propanolol, timolol, pindolol, 
bupranolol, atenolol, metoprolol, practolol; antineoplastics such as 
6-azauridine, cytarabine, floxuridine; antibiotics such as 
chloramphenicol, thiamphenicol, erythromycin, oleandomycin, lincomycin; 
antivirals such as idoxuridine; peripheral vasodilatators such as 
isonicotiny alcohol; carbonic anhydrase inhibitors such as sulocarbilate; 
antiasthmatics and antiinflammatories such as tiaramide; sulfamidics such 
as 2-p-sulfanylanilinoethanol. 
According to the procedure of the present invention 
carboxymethyl-polysaccharide esters may be prepared to advantage by 
starting with quaternary ammonium salts of carboxymethyl-polysaccharide 
acid with an etherifying agent in an organic solvent, preferably aprotic, 
such as inferior alkyl dialkylsulfoxides, especially dimethylsulfoxide, 
and inferior alkyl dialkylamides of aliphatic acids, such as dimethyl or 
diethyl formamide or dimethyl or diethyl acetamide. 
Other solvents too should be considered however, which are not always 
aprotic, such as alcohols, ethers, ketones, esters, especially aliphatic 
or heterocyclic alcohols and ketones with low boiling points, such as 
hexafluoroisopropanol, trifluoroethanol. Reaction is carried out 
preferably within a temperature range of approximately 0.degree. to 
100.degree., and especially between approximately 25.degree. and 
75.degree., for example at about 30.degree.. Esterification is effected 
preferably by gradually adding the esterifying agent to the abovesaid 
ammonium salt dissolved in one of the abovesaid solvents, for example in 
dimethylsulfoxide. The alkylating agents can be those mentioned above, 
especially hydrocarbyl halogens, for example alkyl halogens. As starting 
quaternary ammonium salts it is preferable to use inferior 
tetraalkylammonium salts, with the alkyl groups having preferably between 
1 and 6 carbon atoms. Mainly, the tetrabutylammonium salt of 
carboxymethylpolysaccharide is used. These quaternary ammonium salts can 
be prepared by reacting a metal salt of acidic polysaccharide, preferably 
one of those mentioned above, especially sodium or potassium salt, in 
aqueous solution with a salified sulfonic resin with the quaternary 
ammonium base. Tetraalkylammonium salt of acidic polysaccharide can be 
obtained by freeze-drying the eluate. 
The starting ammonium salts are soluble in the abovesaid aprotic solvents, 
so esterification of acidic polysaccharide is very easy and gives abundant 
yields. By this procedure alone therefore it is possible to exactly dose 
the number of carboxy groups of acidic polysaccharide to be esterified. 
One variation of the previously described procedure consists in reacting 
potassium salt or sodium salt of acidic polysaccharide, suspended in 
suitable solvent, such as dimethylsulfoxide, with a suitable alkylating 
agent in the presence of catalyzing quantities of a quaternary ammonium 
salt, such as tetrabutylammonium iodide. 
The procedure makes it possible to obtain, as we have already said, the 
total esters of acidic polysaccharide, and also of substituted alcohols, 
such as glycols, which have till now been inaccessible. 
The preparation of salts according to the invention can be effected in the 
known way, by bringing together solutions or suspensions, in water or in 
organic solvents, of the two components 1) and 2) and possibly of bases or 
basic salts of the above-said alkaline or alkaline earth metals or 
magnesium or aluminium in calculated quantities and isolating the salts in 
anhydrous amorphous form according to the known techniques. It is possible 
for example to first prepare aqueous solutions of the two components 1) 
and 2), freeing such components of aqueous solutions of their salts with 
suitable ion exchangers, bringing together the two solutions at a low 
temperature, for example between 0.degree. and 20.degree., should the salt 
thus obtained be easily soluble in water it is freeze-dried, while salts 
note easily solubilized can be separated by centrifugation or filtration 
or decantation and possibly subsequently dried. 
For these associated medicaments too the dose is based on that of the 
active principles used singly and can therefore be easily determined by an 
expert on the basis of the doses recommended for the corresponding known 
drugs. 
Of the new products of the present invention particular emphasis should be 
placed on the esters described above and their salts and those featuring 
in the following illustrative examples. 
The present invention also includes modifications in the preparation 
procedure, new esters and their salts, in which a procedure is interrupted 
at any one stage or in which it is begun with an intermediate compound and 
the remaining stages are carried out, or in which the starting products 
are formed in situ.

The invention is illustrated by the following examples, without however 
being limited in any way by the same. 
EXAMPLE 1 
Preparation of the Tetrabutylammonium Salt of Carboxymethylchitin 
10 mEq. of sodium salt of a carboxylmethylchitin with a substitution rate 
of 0.99, prepared according to Trujillo (Carbohydrate Res. 7, 483 (1968), 
corresponding to 2.85 g of dry compound, are solubilized in 300 ml of 
distilled water. The solution is then passed through a thermostatic column 
regulated at 4.degree. C. and containing 15 ml of sulfonic resin (Dowex 
50.times.8) in the form of tetrabutylammonium. 
The sodium-free eluate is freeze-dried. 
Yield: 5.05 g. 
EXAMPLE 2 
Preparation of the Ethyl Ester of a Carboxymethylchitin with a Substitution 
Rate of 0.99 
5.05 g (10 mEq) of tetrabutylammonium salt of a carboxymethylchitin with a 
substitution rate of 0.99 are solubilized in 200 ml of DMSO at 25.degree. 
C. under agitation and in absolutely dry conditions. 
1.56 g (10 mEq) of ethyl iodide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum. 
Yield: 2.90 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 3.41 mEq/g (theoretical 
3.43). 
EXAMPLE 3 
Preparation of the Isopropyl Ester of a Carboxymethylchitin with a 
Substitution Rate of 0.99 
5.05 g (10 mEq) of tetrabutylammonium salt of a carboxymethylchitin with a 
substitution rate of 0.99 are solubilized in 200 ml of DMSO at 25.degree. 
C. under agitation and in absolutely dry conditions. 
1.70 g (10 mEq) of 2-iodopropane are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum. 
Yield: 3.0 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 3.23 mEq/g (theoretical 
3.28). 
EXAMPLE 4 
Preparation of the Benzyl Ester of a Carboxymethylchitin with a 
Substitution Rate of 0.99 
5.05 g (10 mEq) of tetrabutylammonium salt of a carboxymethylchitin with a 
substitution rate of 0.99 are solubilized in 200 ml of DMSO at 25.degree. 
C. under agitation and in absolutely dry conditions. 
1.71 g (10 mEq) of benzyl bromide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 3.5 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.81 mEq/g (theoretical 
2.83). 
EXAMPLE 5 
Preparation of the p-Bromo Benzyl Ester of a Carboxymethylchitin with a 
Substitution Rate of 0.99 
5.05 g (10 mEq) of tetrabutylammonium salt of a carboxymethylchitin with a 
substitution rate of 0.99 are solubilized in 200 ml of DMSO at 25.degree. 
C. under agitation and in absolutely dry conditions. 2.5 g (10 mEq) of 
p-bromobenzyl bromide are added and the solution is agitated overnight at 
30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 4.29 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.29 mEq/g (theoretical 
2.31). 
EXAMPLE 6 
Preparation of the Myristyl Ester of a Carboxymethylchitin with a 
Substitution Rate of 0.99 
5.05 g (10 mEq) of tetrabutylammonium salt of a carboxymethylchitin with a 
substitution rate of 0.99 are solubilized in 200 ml of DMSO at 25.degree. 
C. under agitation and in absolutely dry conditions. 
2.77 g (10 mEq) of myristylbromide are added and the solution is agitated 
overnight at 30.degree. C. 1000 ml of ethyl acetate are slowly added drop 
by drop, the precipitate is separated by filtration and washed 3 times 
with 100 ml of ethyl acetate, then dried in high vacuum 
Yield: 4.57 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.16 mEq/g (theoretical 
2.18). 
EXAMPLE 7 
Preparation of the Tetrabutylammonium Salt of a Carboxymethylcellulose with 
a Substitution Rate of 0.75 and Low Viscosity 
10 mEq of sodium salt of a carboxymethylcellulose with a substitution rate 
of 0.75 and low viscosity (30 mPa.s, solution at 2% in distilled water at 
20.degree. C. by Hoppler viscosimeter), corresponding to 2,96 g of dry 
compound, are solubilized in 300 ml of distilled water. The solution is 
then passed through a thermostatic column regulated at 4.degree. C. and 
containing 15 ml of sulfonic resin (Dowex 50.times.8) in the form of 
tetrabutylammonium. 
The sodium-free eluate is freeze-dried. 
Yield: 5.05 g. 
EXAMPLE 8 
Preparation of the Ethyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and Low Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and low viscosity, prepared as in example 7, 
are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and in 
absolutely dry conditions. 1.56 g (10 mEq) of ethyl iodide are added and 
the solution is agitated overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 2.91 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 3.30 mEq/g (theoretical 
3.31). 
EXAMPLE 9 
Preparation of the Isopropyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and Low Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and low viscosity, prepared as in example 7, 
are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and in 
absolutely dry conditions. 
1.70 g (10 mEq) of 2-iodopropane are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 3.02 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 3.12 mEq/g (theoretical 
3.16). 
EXAMPLE 10 
Preparation of the Isopropyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and Low Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and low viscosity, prepared as in example 7, 
are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and in 
absolutely dry conditions. 
1.71 g (10 mEq) of benzyl bromide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 3.54 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.70 mEq/g (theoretical 
2.74). 
EXAMPLE 11 
Preparation of the p-Bromobenzyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and Low Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and low viscosity, prepared as in example 7, 
are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and in 
absolutely dry conditions. 
2.5 g (10 mEq) of p-bromobenzyl-bromide are added and the solution is 
agitated overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 4.35 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.25 mEq/g (theoretical 
2.28). 
EXAMPLE 12 
Preparation of the Myristyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and Low Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and low viscosity, prepared as in example 7, 
are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and in 
absolutely dry conditions. 
2.77 g (10 mEq) of myristyl bromide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 4.61 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.12 mEq/g (theoretical 
2.15). 
EXAMPLE 13 
Preparation of the Tetrabutylammonium Salt of a Carboxymethylcellulose with 
a Substitution Rate of 0.75 and Medium Viscosity 
10 mEq of sodium salt of a carboxymethylcellulose with a substitution rate 
of 0.75 and medium viscosity (30 mPa.s, solution at 2% in distilled water 
at 20.degree. C. by Hoppler viscosimeter), corresponding to 2,96 g of dry 
compound, are solubilized in 300 ml of distilled water. The solution is 
then passed through a thermostatic column regulated at 4.degree. C. and 
containing 15 ml of sulfonic resin (Dowex 50.times.8) in the form of 
tetrabutylammonium. 
The sodium-free eluate is freeze-dried. 
Yield: 5.00 g. 
EXAMPLE 14 
Preparation of the Ethyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and Medium Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and medium viscosity, prepared as in example 
13, are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and 
in absolutely dry conditions. 
1.56 g (10 mEq) of ethyl iodide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 2.93 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 3.24 mEq/g (theoretical 
3.31). 
EXAMPLE 15 
Preparation of the Isopropyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and Medium Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and medium viscosity, prepared as in example 
13, are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and 
in absolutely dry conditions. 
1.7 g (10 mEq) of 2-iodopropane are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 3.1 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 3.11 mEq/g (theoretical 
3.16). 
EXAMPLE 16 
Preparation of the Benzyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and Medium Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and medium viscosity, prepared as in example 
13, are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and 
in absolutely dry conditions. 1.71 g (10 mEq) of benzyl bromide are added 
and the solution is agitated overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 3.04 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.70 mEq/g (theoretical 
2.74). 
EXAMPLE 17 
Preparation of the p-Bromo Benzyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and Medium Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and medium viscosity, prepared as in example 
13, are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and 
in absolutely dry conditions. 
2.5 g (10 mEq) di p-bromobenzyl bromide are added and the solution is 
agitated overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 4.32 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group 
EXAMPLE 18 
Preparation of the Myristyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and Medium Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and medium viscosity, prepared as in example 
13, are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and 
in absolutely dry conditions. 
2.77 g (10 mEq) of myristyl bromide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 4.61 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.12 mEq/g (theoretical 
2.15). 
EXAMPLE 19 
Preparation of the Tetrabutylammonium Salt of a Carboxymethylcellulose with 
a Substitution Rate of 0.75 and High Viscosity 
10 mEq of sodium salt of a carboxymethylcellulose with a substitution rate 
of 0.75 and high viscosity (6000 mPa.s, solution at 2% in distilled water 
at 20.degree. C. by Hoppler viscosimeter), corresponding to 2.96 g of dry 
compound, are solubilized in 300 ml of distilled water The solution is 
then passed through a thermostatic column regulated at 4.degree. C. and 
containing 15 ml of sulfonic resin (Dowex 50.times.8) in the form of 
tetrabutylammonium. 
The sodium-free eluate is freeze-dried. 
Yield: 4.95 g. 
EXAMPLE 20 
Preparation of the Ethyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and High Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and high viscosity, prepared as in example 19, 
are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and in 
absolutely dry conditions. 
1.56 g (10 mEq) of ethyl iodide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 2.91 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 3.30 mEq/g (theoretical 
3.31). 
EXAMPLE 21 
Preparation of the Isopropyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and High Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and high viscosity, prepared as in example 19, 
are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and in 
absolutely dry conditions. 
1.7 g (10 mEq) of 2-iodopropane are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 3.02 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 3.07 mEq/g (theoretical 
3.16). 
EXAMPLE 22 
Preparation of the Benzyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and High Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and high viscosity, prepared as in example 19, 
are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and in 
absolutely dry conditions. 
1.71 g (10 mEq) of benzyl bromide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 3.46 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.72 mEq/g (theoretical 
2.74). 
EXAMPLE 23 
Preparation of the p-Bromo Benzyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and High Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and high viscosity, prepared as in example 19, 
are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and in 
absolutely dry conditions. 
2.5 g (10 mEq) of p-bromobenzyl bromide are added and the solution is 
agitated overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 4.28 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.26 mEq/g (theoretical 
2.28). 
EXAMPLE 24 
Preparation of the Myristyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 0.75 and High Viscosity 
5.15 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 0.75 and high viscosity, prepared as in example 19, 
are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and in 
absolutely dry conditions. 
2.77 g (10 mEq) of myristyl bromide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 4.54 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.11 mEq/g (theoretical 
2.15). 
EXAMPLE 25 
Preparation of the Tetrabutylammonium Salt of a Carboxymethylcellulose with 
a Substitution Rate of 1.0 and Medium Viscosity 
10 mEq of sodium salt of a carboxymethylcellulose with a substitution rate 
of 1.0 and medium viscosity (200 mPa.s, solution at 2% in distilled water 
at 20.degree. C. by Hoppler viscosimeter), corresponding to 2,42 g of dry 
compound, are solubilized in 300 ml of distilled water. The solution is 
then passed through a thermostatic column regulated at 4.degree. C. and 
containing 15 ml of sulfonic resin (Dowex 50.times.8) in the form of 
tetrabutylammonium. 
The sodium-free eluate is freeze-dried. 
Yield: 4.6 g. 
EXAMPLE 26 
Preparation of the Ethyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 1.0 and Medium Viscosity 
4.62 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 1.0 and medium viscosity, prepared as in example 
25, are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and 
in absolutely dry conditions. 
1.56 g (10 mEq) of ethyl iodide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield 2.44 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 4.0 mEq/g (theoretical 
4.03) 
EXAMPLE 27 
Preparation of the Isopropyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 1 0 and Medium Viscosity 
4.62 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 1.0 and medium viscosity, prepared as in example 
25, are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and 
in absolutely dry conditions. 
1.70 g (10 mEq) of 2-iodopropane are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 2.58 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 3.69 mEq/g (theoretical 
3.81). 
EXAMPLE 28 
Preparation of the Benzyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 1.0 and Medium Viscosity 
4.62 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 1.0 and medium viscosity, prepared as in example 
25, are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and 
in absolutely dry conditions. 
1.71 g (10 mEq) of benzyl bromide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 3.05 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 3.15 mEq/g (theoretical 
3.22) 
EXAMPLE 29 
Preparation of the p-Bromobenzyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 1.0 and Medium Viscosity 
4.62 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 1.0 and medium viscosity, prepared as in example 
25, are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and 
in absolutely dry conditions. 
2.5 g (10 mEq) of p-bromobenzyl bromide are added and the solution is 
agitated overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 3.85 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group 
EXAMPLE 30 
Preparation of the Myristyl Ester of a Carboxymethylcellulose with a 
Substitution Rate of 1.0 and Medium Viscosity 
4.62 g (10 mEq) of tetrabutylammonium salt of a carboxymethylcellulose with 
a substitution rate of 1.0 and medium viscosity, prepared as in example 
25, are solubilized in 200 ml of DMSO at 25.degree. C. under agitation and 
in absolutely dry conditions. 
2.77 g (10 mEq) of myristyl bromide are added and the solution is agitated 
overnight at 30.degree. C. 
1000 ml of ethyl acetate are slowly added drop by drop, the precipitate is 
separated by filtration and washed 3 times with 100 ml of ethyl acetate, 
then dried in high vacuum 
Yield: 4.12 g. 
Quantitative determination of the ester groups is carried out according to 
the saponification method described on pages 169-172 of "Quantitative 
Organic Analysis Via Functional Groups" 4th Edition, John Wiley and Sons 
Publication and shows an ester group content of 2.36 mEq/g (theoretical 
2.4). 
As discussed above, the new polysaccharide esters of the invention are 
useful for the preparation of pharmaceutical formulations and new medical 
articles. The following are particular exemplary pharmaceutical 
preparations according to the invention. 
Formulation 1 
Collirium containing cortisone of which 100 ml contain: 
Partial ester of carboxymethylcellulose with cortisone, gr. 0.200 
ethyl p. hydroxybenzoate, gr. 0.010 
methyl p. hydroxybenzoate, gr. 0.050 
sodium chloride, gr. 0.900 
water for injectable preparations/q.b.a., ml. 100 
Formulation 2 
Injectable solution containing hydrocortisone of which 100 ml contain: 
partial ester of carboxymethylchitin with hydfocortisone, gr. 0.1 
water for injectable preparations/q.b.a., ml. 100 
Formulation 3 
Cream containing a partial ester of carboxymethylcellulose with ethyl 
alcohol, of which 100 gr. contain: 
partial ester of carboxymethylcellulose acid with ethyl alcohol, gr. 0.2 
Polyethyleneglycol monostearate 400, gr. 10.000 
Cetiol V. gr. 5.000 
Lanette SX, gr. 2.000 
Paraoxybenzoate of methyl, gr. 0.075 
Paraoxybenzoate of propyl, gr. 0.050 
Sodium dihydroacetate, gr. 0.100 
Glycerine F.U., gr. 1.500 
Sorbitol 70, gr. 1.500 
Test cream, gr. 0.050 
Water for injectable preparations/q.b.a., gr. 100.00 
The following preparations exemplify the medical articles according to the 
invention containing the alginic esters. 
EXAMPLE 31 
Preparation of Films Using Esters of Carboxymethylcellulose 
A solution is prepared in dimethylsulfoxide of the n-propyl ester of 
carboxymethylcellulose. 
By means of a stratifier, a thin layer of solution is spread on a glass 
sheet; the thickness must be 10 times greater than the final thickness of 
the film. The glass sheet is immersed in ethanol which absorbs the 
dimethylsulfoxide but does not solubilize the carboxymethylcellulose ester 
which becomes solid. The film is detached from the glass sheet, is 
repeatedly washed with ethanol, then with water and then again with 
ethanol. 
The resulting sheet is dried in a press for 48 hours at 30.degree.. 
EXAMPLE 32 
Preparation of Threads Using Esters of Carboxymethylcellulose 
A solution is prepared in dimethylsulfoxide of the benzyl ester of 
carboxymethylcellulose. The solution thus obtained is pressed by means of 
a pump through a threader with 0.5 mm holes. 
The threader is immersed in ethanol/dimethylsulfoxide 80:20 (this 
concentration is kept constant by continuous addition of ethanol); when 
the solution in dimethylsulfoxide is soaked in this way it tends to lose 
most of the dimethylsulfoxide and the thread solidifies. 
The thread is stretched while it still has a content of dimethylsulfoxide, 
is then repeatedly stretched and washed with ethanol The thread is dried 
in nitrogen current. 
EXAMPLE 33 
Preparation of a Spongy Material Made with Esters of Carboxymethylcellulose 
1 g of benzyl ester of carboxymethylcellulose in which all the carboxylic 
groups are esterified (obtained for example as described in Example 22) 
are dissolved in 5 ml of dimethylsulfoxide. To each 10 ml of solution 
prepared, a mixture of 31.5 g of sodium chloride with a degree of 
granularity corresponding to 300.mu., 1.28 g of sodium bicarbonate and 1 g 
of citric acid is added and the whole is homogenized in a mixer. 
The pasty mixture is stratified in various ways, for instance by means of a 
mange consisting of two rollers which turn opposite each other at an 
adjustable distance between the two. Regulating this distance the paste is 
passed between the rollers together with a strip of silicone paper which 
acts as a support to the layer of paste thus formed. The layer is cut to 
the desired dimensions of length and breadth, removed from the silicone, 
wrapped in filter paper and emerged in a suitable solvent, such as water. 
The sponges thus obtained are washed with a suitable solvent such as water 
and possibly sterilized with gamma rays. 
EXAMPLE 34 
Preparation of a Spongy Material Made with Esters of Carboxymethylcellulose 
In the manner described in Example 33, it is possible to prepare spongy 
materials with other carboxymethylcellulose esters. In the place of 
dimethylsulfoxide it is possible to use, if desired, any other solvent 
capable of dissolving the chosen ester. In the place of sodium chloride it 
is possible to use any other solid compound which is insoluble in the 
solvent used to dissolve the carboxymethylcellulose ester, but which is 
soluble in the solvent used to precipitate the carboxymethylcellulose 
ester after the above mentioned mechanical treatment, and finally which 
has the correct degree of granularity to obtain the type of pores desired 
in the sponge material. 
In the place of sodium bicarbonate and citric acid it is possible to use 
other couples of similar compounds, that is, compounds which react to each 
other in suspension or solution of the solvent used to dissolve 
carboxymethylcellulose in such a way as to form a gas, such as carbon 
dioxide, which has the effect of producing a less compact spongy material. 
In this way it is possible to use, in the place of sodium bicarbonate, 
other bicarbonates or alkaline or alkaline earth carbonates and in the 
Place of citric acid other acids in solid form, such as tartaric acid. 
The invention being thus described, it will be obvious that the same may be 
varied in many ways. Such variations are not to be regarded as a departure 
from the spirit and scope of the invention, and all such modifications as 
would be obvious to one skilled in the art are intended to be included 
within the scope of the following claims.