DE3914428A1 - METHOD FOR PRODUCING GELATINE / CYCLODEXTRIN POLYMERS AND GELATINE / CYCLODEXTRIN COPOLYMERS - Google Patents

Abstract

There is described a process for the preparation of gelatine/cyclodextrin copolymers, comprising a) reacting, per gram of gelatin, 1.5 to 15 mmol of epichlorohydrin or 0.1 to 2.5 mmol of diglycidyl ether of formula (I> <IMAGE> or a linking agent of general formula (II) or (III), <IMAGE> wherein m, R and Y as herein described and 0.05 to 3.0 mmol of cyclodextrin or a substituted cyclodextrin of general formula (IV), CD-(OQX)m (IV> wherein CD, Q and X are herein defined or 0.1 to 20 g of a water-soluble cyclodextrin polymer of general formula (V> <IMAGE> wherein R<1>, R<2>, R<3>, R<4>, CD, P and n are herein defined with gelatin or b) reacting 0.2 to 2.0 mmol of a compound of general formula (VI), or (VII), or (VIII), <IMAGE> wherein X<1>, m, R<2> and R<5> are herein defined and 0.03 to 3.5g of gelatine and 5 to 15 mmol of epichlorohydrin or 1.0 to 5.0 mmol of a diglycidyl ether of formula (I) or a linking agent of the general formula (II) or (III) per mol of cyclodextrin with cyclodextrin.

Description

The invention relates to a new method to carry out the reaction of gelatin with cyclodextrin and its derivatives, as well as with water-soluble cyclodextrin polymers, as well as the products available from it.

Gelatin is used in large quantities in the Food, pharmaceutical and photochemical Industry applied. In order to improve or Modification of your chemical, physico-chemical and mechanical properties become their most suitable Functional groups, d. H. the amino and carboxyl groups implemented with different reagents. So be in order Modification: their amino groups with organic acid halides or anhydrides (e.g. benzenesulfonyl chloride, Acetic anhydride, etc.), with isothiocyanates, with activated halogen-containing compounds (e.g. with Benzene bromide, haloacetic acids, chlorine derivatives of s-triazines, pyrimidines and pyrazines, etc.), or with Reacted epoxides; the carboxyl groups will esterified; the hydroxyl groups are remodeled to sulfate esters and by acylation in an anhydrous Medium modified. All of these possibilities are in the Literature discussed in detail (A.G. Ward and A. Courts: The Science and Technology of Gelatin, Academic Press, London 1977, pages 212 to 223). A special method of Modification of the gelatin consists in the copolymerization (Grafting) with acrylic monomers caused by acrylamide,  Methacrylamide, acrylic acid, methacrylic acid, methyl methacrylate, Butyl acrylate etc. in an aqueous medium, in the presence of an initiator, such as a peroxysulfate, Benzoyl peroxide, acetyl peroxide or perborate, etc. realized will [R. J. Croome: J. Phot. Sci. 30, 181 (1982)].

To modify the gelatins were Cyclodextrin and its derivatives have not yet been used.

The cyclodextrins are cyclic, non-reducing oligosaccharides formed from α- D-glucopyranose units by 1,4-glucoside bonds, which are known everywhere for their ability to form inclusion complexes (J. Szejtli: Cyclodextrin and their Inclusion Complexes, Akad´miai Kiadó, Budapest, 1982). Which consist of 6, 7 or 8-glucopyranoses α -, β - or γ-cyclodextrins prepared by enzymatic degradation of starch.

A high number of cyclodextrin derivatives, such as ethers, esters, nitrogen, sulfur and halogen-containing Compounds, acid derivatives, etc. have been synthesized (see J. Szejtli, ibid. pages 81 to 89). The responsiveness of those in the cyclodextrin molecules primary and secondary alcoholic hydroxyl groups enables water-soluble polymers with a medium average molecular size. According to one Method becomes a polymerizable and unsaturated Derivative made from cyclodextrin, and this is then in itself or with a cyclodextrin not containing  Monomer polymerized together [J. Polym. Sci. Letters 13, 357 (1975)]. According to another procedure, the Cyclodextrin molecules by appropriate bifunctional Reagents, e.g. B. diepoxides or epichlorohydrin to one containing linear or branched chains, but none Cross-linked structure, water-soluble polymers Product (Hungarian Patent No. 1 80 597, 1982) or to one substituted by ionic groups, coupled water-soluble cyclodextrin polymer (Hungarian Patent Specification No. 1 91 101, 1983). Water soluble polymers can also be obtained in such a way that from a polymerizable cyclodextrin monomer derivative, e.g. B. Cyclodextrin acrylic esters, or cyclodextrin to one other polymer (see J. Szejtli, ibid. pages 88 to 91).

The coupling of cyclodextrins and their Derivatives to gelatin have not yet been described.

The aim of the invention is a water-soluble To produce copolymer which has the properties of Gelatin and cyclodextrin combined.

The invention is based on the knowledge that that a chemical reaction between cyclodextrin or its derivatives and gelatin by the application of a suitable coupling means can be realized.

Furthermore, the invention is based on the Realization that chemical, physico-chemical  and mechanical properties of the polymer formed in the modified by cyclodextrin or its derivatives Gelatin through the gelatin / cyclodextrin ratio can be regulated.

Coupling the gelatin with cyclodextrin or its derivatives can be carried out in two ways will:

• 1) Cyclodextrin or a substituted one Cyclodextrin and gelatin are left with the coupling agent react; or
• 2) A water soluble cyclodextrin polymer and gelatin is allowed to react with the coupling agent.

According to the invention, one proceeds in such a way that 1.5 to 15 mmol of epichlorohydrin or 0.1 to 2.5 mmol Diglycidyl ether of formula (I)

or a coupling agent of the general formula (II) or (III)

- if necessary, an initiator when using (III) - and 0.05 to 3.0 mmol cyclodextrin or substituted cyclodextrin of the general formula (IV)

CD- (OQX) _m (IV)

or 0.1 to 20 g of water soluble cyclodextrin polymer of the general formula (V)

reacted with 1 g of gelatin.

According to the invention, one can also do this procedure that 0.2 to 2.0 mmol of the compound of general formula (VI) or (VII) or (VIII)

X ′ - (CH₂) _m -COOH (VI)
H₂N- (CH₂) _m -COOH (VII)
R₂ = N-R⁶ (VIII)

further 0.03 to 3.5 g of gelatin and 5 to 15 mmol Epichlorohydrin or 1.0 to 5.0 mmol of diglycidyl ether Formula (I) or a coupling agent of general formula (II) or (III) - optionally one Initiator when using (III) - with 1 mmol cyclodextrin implements.  

In both methods according to the invention can by-products of the reaction and the water be removed if necessary.

In the above formulas:

R is hydrogen or a C _1-5 alkyl group;
Y chlorine, bromine, NH₂ or C _1-2 alkoxy, e.g. B. methoxy, ethoxy, n or isopropoxy group;
Q is a - (CH₂) _m group;
X is hydrogen or CO₂H, NH₂, NR², OH or SO₃H group;
R1 is a bridge coupling the cyclodextrin molecules in the polymer chain through an ether linkage, the constituent of which is the coupling agent;
R² is hydrogen or a substituent identical to R³;
R³ is an OH, -CD · a R⁴, OR⁵, O (CH₂) _m OR⁵, (OCH₂CH₂) _m OR⁵, NR², -NH (CH₂) _m -CO₂H group;
R⁴-R¹ · R²,

or a substituent identical to R⁵;
R⁵ is hydrogen or - (CH₂) _m -CO₂H, H₂N- (CH₂) _m group;
R⁶ is hydrogen or - (CH₂) _m -Cl or - (CH₂) _m group;
X, chlorine or bromine;
CD is an α, β or γ cyclodextrin molecule;
a is an integer from zero to a value one unit lower than the original number of hydroxyl groups of the cyclodextrin;
m is a number from 1 to 6;
n is a number from 2 to 12; and
p zero or a number that is at least two units lower than the original number of hydroxyl groups of the cyclodextrin.

In the method according to the invention can both chalky gelatins with a low isoelectric point, as well as by means of an acid process made gelatins with a high isoelectric point be used.

In addition to the α-, β- and γ- cyclodextrin monomers, their substituted derivatives, e.g. B. the carboxymethyl, diethylaminoethyl, dimethyl, trimethyl, hydroxypropyl, sulfopropyl or sulfobutyl group containing cyclodextrins, and water-soluble cyclodextrin polymers, e.g. B. the unsubstituted α-, β- or γ- cyclodextrin polymer or the carboxymethyl, diethylaminoethyl, carboxypropyl- γ- amino group can be used alone or together with water-soluble cyclodextrin polymers.

Before coupling with the gelatin, halogenated carboxylic acids, such as. B. chloroacetic acid, bromoacetic acid, chloropropionic acid, etc .; Amino acids, e.g. B. β- aminopropionic acid, or γ- aminobutyric acid, etc .; Alkylamines, e.g. B. dimethylamine, diethylamine, dibutylamine or alkylaminoethylchloride, e.g. As diethylaminoethyl chloride, etc. can be used to substitute the monomer.

As a coupling agent, one can also Epichlorohydrins and Diglycidylether the homologues of Diglycidyl ether such as ethylene or butylene diglycidyl ether, as well as unsaturated carboxylic acid chlorides and carboxylic acid esters, e.g. B. apply methacryloyl chloride or methyl methacrylate.

As initiators such. B. potassium persulfate, Hydrogen peroxide, benzoyl peroxide, etc. are used.

In the method according to the invention can that reaction product both as a solution as well be obtained in solid form. If necessary, they can Chloride ions and products with a lower molecular weight by performing on an ion exchange Column or removed by dialysis. From the solution, which is ion-free or contains the by-products of the reaction, the solid can be precipitated with a solvent, e.g. B. alcohol or acetone can be recovered. Copolymers, which due to their sufficient gelatin content to one Gel can be converted after crushing of the gel can be cleaned by an aqueous wash.

All of the coupling agents listed occur with the amino and / or carboxyl groups of the gelatin in reaction. A method of controlling the coupling reaction consists in the acid-base titration of the ionizing Groups of gelatin, reducing the number of reacting groups can be determined [P. Lanza and I. Mazzei: Annali di Chimica 53, 1833 (1963)].  

The coupling of the gelatin with cyclodextrin by the coupling agent can also be followed by measuring the optical rotatory power. This is due to the fact (see Fig. 1) that the solution of a mechanical mixture with different ratios of gelatin and cyclodextrin, or cyclodextrin polymer (curves 1 a and 2 a) gives a more negative specific turning power than the copolymer which works with the same Gelatin / cyclodextrin ratio was produced (curves 1 b and 2 b) . (Explanation of the curves: 1 a : mixture; 1 b ; copolymer, both contain 80 mass% gelatin and 20 mass% cyclodextrin; 2 a : mixture; 2 b : copolymer, both contain 20 mass% gelatin and 80 mass% cyclodextrin) . This phenomenon may be related to the fact that a certain proportion of the gelatin molecules incorporated into the copolymer lose the isomerization ability in the proline-hydroxyprolyne bonds.

The characteristics of the in the reaction of the Gelatin, coupling agent and cyclodextrin resulting copolymers depend everywhere on the gelatin-cyclodextrin ratio from. Is that calculated on monomer Cyclodextrin in relation to gelatin predominantly, then The solubility increases by leaps and bounds, even a 50% solution can be made at room temperature, d. H. that the copolymer dissolves better in water than the starting substances. On the contrary, one of the reversible sol-gel forms  Product capable of transformation with the increase of Gelatin ratio. In both cases, the Copolymers have the ability to form inclusion complexes to form, the degree of which depends on the cyclodextrin content.

The advantages of the invention Procedures are as follows.

• 1) A water soluble, for the formation of Inclusion complex suitable polymer can be made which is capable of reversible sol-gel conversion.
• 2) A polymer containing cyclodextrin can be obtained, the water solubility of which the ordinary cyclodextrin polymer.
• 3) The means of the invention Processed product has better physical Properties than the gelatin.

The inventive method is in following explained in more detail with reference to exemplary embodiments, without restricting the invention to these examples. (In these examples, cyclodextrin is abbreviated to Labeled "CD").

example 1

The pH of 100 ml of 10% gelatin solution [with an isoelectric point (abbreviated: IEP) of 4.8] is adjusted to 10.5 by adding 40% sodium hydroxide solution, 0.013 mol of β- CD are added and then, 0.13 mol of epichlorohydrin was added dropwise while the temperature was kept at 60 ° C. The reaction mixture is stirred at the same temperature for one hour, then cooled and the pH is adjusted to 6.5 by 10% hydrochloric acid. The solution is evaporated in vacuo to a third of its volume, the product is precipitated by alcohol, washed and dried.

Example 2

The procedure is as in Example 1, except that γ- CD instead of β- CD and 0.16 mol of epichlorohydrin are used.

Example 3

The procedure is as in Example 1, except that 0.010 mol of α- CD instead of β- CD and 0.10 mol of epichlorohydrin are used.

Example 4

The procedure is as in Example 1, except that 0.005 mol of β- CD and 0.10 mol of epichlorohydrin are used.

Example 5

The procedure is as in Example 1, except that 0.005 mol of β- CD and 0.05 mol of epichlorohydrin are used.

Example 6

The pH of 100 ml of 10% gelatin solution with a high izoelectric point (IEP = 8.2) is adjusted to 10 by 40% sodium hydroxide solution, 100 ml 20% solution of β- CD polymer (abbreviated: β - CDP (with a polymeric CD content of 56%) are added and then 0.015 mol of epichlorohydrin are added dropwise. The reaction mixture is stirred at 58 ° C for 45 minutes and then Example 1 is followed.

Example 7

The procedure is as in Example 6, except that 100 ml of a 10% solution of cyrboxymethyl- β- cyclodextrin polymer (abbreviated: CM- β- CDP; with a polymeric CD content of 59%) is used instead of CDP.

Example 8

The procedure is as in Example 7, except that 0.050 mole of epichlorohydrin is used.

Example 9

The procedure is as in Example 7, except that 0.015 mol of epichlorohydrin and 1.0 g of CM- β- CDP (with a polymeric CD content of 59%) are used.

Example 10

The procedure is as in Example 6, except that 100 ml of a 10% solution of diethylamino- β- cyclodextrin polymer (DEA- β- CDP; with a polymer CD content of 59%) is used.

Example 11

0.013 mol of diglydicidyl ether (DGE) is added to 100 ml of 10% solution of gelatin with a low isoelectric point (IEP = 4.8) while stirring at 55 ° C. and then stirred for a further 30 minutes. Then 0.012 mol of β- CD is added, the pH is adjusted to 11 with 40% sodium hydroxide solution and the reaction mixture is stirred at 60 ° C. for one hour. Then the solution is neutralized by 10% hydrochloric acid and the third is evaporated in vacuo. The yellow mass precipitated during cooling is dissolved in distilled water, precipitated by adding alcohol, filtered and dried.

Example 12

The procedure is as in Example 11, except that β- CD is used instead of β- CD.

Example 13

The procedure is as in Example 11, except that γ- CD instead of β- CD is implemented.

Example 14

The procedure is as in Example 11, except that 0.0065 mol of DGE, 7.62 g of sulfobutyl- β- cyclodextrin (abbreviated: SB- β- CD) and a gelatin with a high isoelectric point (IEP = 8.2 ) used, and the pH of the reaction mixture is adjusted to 8.5 with 40% sodium hydroxide solution.

Example 15

The procedure is as in Example 14, except that 8.54 pentakis (carboxymethyl) - β- cyclodextrin (abbreviated: PCM- β- CD) is used instead of SB- β- CD.

Example 16

One swells, then 10 g of gelatin (IEP = 4.8) is dissolved in 150 ml of distilled water. After the addition of 0.003 mol of DGE, the solution is stirred at its own pH at 40 ° C. for 10 minutes. 0.015 mol of β- CD is introduced into 50 ml of distilled water and dissolved in 40% sodium hydroxide solution. The alkaline β- CD solution is dropped into the gelatin solution over a period of 5 minutes, the temperature is set at 55 to 60 ° C., the reaction mixture is stirred at the same temperature for 1 hour and left to stand for one night. The pH is adjusted to 6.5 with 10% hydrochloric acid, the solution is evaporated to half its volume in vacuo, the solid is precipitated by adding alcohol, then washed and dried.

Example 17

The procedure is as in Example 16, except that one uses 0.015 mol DGE.

Example 18

Example 16 is followed with the exception that 30.9 g of CM- β- CDP (with a polymeric CD content of 55%) is added to 100 ml of water instead of β- CD and dissolved by adding 40% sodium hydroxide solution.

Example 19

Example 18 is followed with the exception that 0.015 mole of DGE is used.

Example 20

Example 16 is followed with the exception that 57.7 g of CM- β- CDP (with a polymeric CD content of 59%) instead of β- CD is dissolved in 150 ml of water by adding 40% sodium hydroxide solution and a gelatin with a high isoelectric point (IEP = 8.2) can be used.

Example 21

Example 20 is followed with the exception that 0.025 mole of DGE is used.

Example 22

Example 20 is followed with the exception that 5 g of gelatin with a high isoelectric point be used.

Example 23

Example 16 is followed with the exception that 0.015 mol of butylene diglycidyl ether (abbreviated: BDE) [compound of the general formula (II), m = 4] is used instead of DGE.

Example 24

Example 23 is followed with the exception that 0.050 mole BDE and 0.025 mole β- CD are reacted.

Example 25

Example 16 is followed with the exception that 100 ml of 5% gelatin solution and 0.015 mol BDE are used instead of DGE and 45 g of CM- β- CDP (with a polymeric CD content of 57%) in 150 ml instead of β- CD Water dissolved by adding 40% sodium hydroxide solution.

Example 26

Example 25 is followed with the exception that 100 ml of 10% gelatin solution, 25 g of CM- β- CDP (with a polymeric CD content of 57%) and 0.022 mol of BDE are reacted.

Example 27

Example 25 is followed with the exception that 100 ml of 10% solution of a gelatin with a high isoelectric point (IEP = 8.2), 5 g of CM- β- CDP (with a polymeric CD content of 57%) and 0.015 Mol BDE can be implemented.

Example 28

Example 25 is followed with the exception that 100 ml of 10% gelatin solution, 1 g of CM- β- CDP (with a polymeric CD content of 57%) and 0.025 mol of BDE are used.

Example 29

0.018 mol of β- CD is added to 100 ml of 10% inert gelatin solution at 40 ° C, the pH of the solution is adjusted to 10.5 by adding 40% sodium hydroxide solution, the temperature is increased to 58 ° C and 0.025 mol Methacryloyl chloride [compound of general formula (III), wherein R = CH₃ and Y = Cl] is added dropwise with stirring. The mixture is further stirred at the same temperature for 30 minutes, then the mixture is cooled to 40 ° C., the solid is precipitated with acetone, washed and dried.

Example 30

Example 29 is followed with the exception  that also 8 ml of 1% potassium persulfate solution of the gelatin solution be added.

Example 31

Example 29 is followed with the exception that γ- CD instead of β- CD and a gelatin with a high isoelectric point (IEP = 8.2) are used and the pH of the reaction mixture is adjusted to 8.5 by adding sodium hydroxide solution becomes.

Example 32

100 ml of 10% CM- β- CDP solution (with a CD content of 57%) are added to 100 ml of 10% inert gelatin solution. The temperature is set to 60 ° C., 0.025 mol of methacryloyl chloride is added dropwise with stirring, then the mixture is stirred for a further 30 minutes. After the reaction mixture has cooled to 40 ° C., the solid is precipitated with acetone, washed and dried.

Example 33

Example 32 is followed with the exception that 100 ml of 5% inert gelatin solution and 0.005 mol Methacryloyl chloride can be used.

Example 34

Example 32 is followed with the exception that 100 ml of 1% inert gelatin solution, 100 ml of 20% solution of CM- β- CDP and 0.001 mol of methacryloyl chloride are used.

Example 35

3.42 g (0.036 mol) of chloroacetic acid are added to 30 ml of 6% sodium hydroxide solution, then 0.018 mol of β- CD is sprinkled in with stirring. After stirring for 20 minutes, 30 ml of 6% sodium hydroxide solution are added dropwise, the temperature is raised to 58 ° C. and the reaction mixture is stirred at the same temperature for 70 minutes. Then 50 ml of 3% inert gelatin solution are poured in, the pH is adjusted to 10.5 by adding 20% sodium hydroxide solution and then 7 ml (0.045 mol) of BDE are added dropwise at 60 ° C. Stirring is continued at the same temperature for 30 minutes. The pH is adjusted to 6.5 by 10% hydrochloric acid solution, the solution is evaporated in half in vacuo, the solid is precipitated with acetone, washed and dried.

Example 36

Example 35 is followed with the exception that 0.342 g (0.0036 mol) of chloroacetic acid and 200 ml 10% inert gelatin solution can be used.

Example 37

Example 35 is followed with the exception that 300 ml of 12% inert gelatin solution are used.

Example 38

Example 35 is followed with the exception that 1.026 g (0.0108 mol) of chloroacetic acid, 50 ml of 1% Inert gelatin solution and 0.27 mol epichlorohydrin (instead of BDE) be used.  

Example 39

Example 38 is followed with the exception that 0.18 mol of epichlorohydrin is used.

Example 40

Example 35 is followed with the exception that 0.09 mol of epichlorohydrin and a gelatin with a high isoelectric point (IEP = 8.2) can be used.

Example 41

0.018 mol of β- CD is dissolved in 45 ml of 20% sodium hydroxide solution, 0.035 mol of γ- aminobutyric acid is added and the temperature is raised to 50 ° C. Then 50 ml of 3% inert gelatin solution are poured in, the pH is adjusted to 10.5 by adding 40% sodium hydroxide solution and 0.18 mol of epichlorohydrin is added dropwise while stirring, while the temperature is kept at a maximum of 60 ° C. Then the reaction mixture is further stirred at 60 ° C. for one hour. The pH is adjusted to 6.5 by adding 10% hydrochloric acid, then the solution is evaporated in half in vacuo, the solid is precipitated with acetone, washed and dried.

Example 42

Example 41 is followed with the exception the 150 ml 10% inert gelatin solution and 0.13 mol epichlorohydrin be used.

Example 43

Example 41 is followed except that 0.030 mole of diethylamine is used in place of the γ- aminobutyric acid.

Example 44

Example 43 is followed with the exception that 0.020 mol of diethylamine and 200 ml of 10% inert gelatin solution be used.

Example 45

The procedure is as in Example 35, except that no more amount of sodium hydroxide solution to the reaction mixture after adding the gelatin solution and 0.045 mol Methacryloyl chloride used instead of BDE.

Example 46

The procedure is as in Example 45, except that you have 200 ml of 10% inert gelatin solution and 0.018 mol Methacryloyl chloride used.

Example 47

The procedure is as in Example 45, except that 0.090 mole of methacryloyl chloride and a gelatin with a high isoelectric point (IEP = 8.2).

Example 48

The procedure is as in Example 45, except that you have 200 ml of 20% gelatin solution and 0.018 mol Methacryloyl chloride used.

Example 49

The procedure is as in Example 45, except that 300 ml of 20% inert gelatin solution and 0.018 mol Reacts methacryloyl chloride.  

Example 50

The procedure is as in Example 45, except that 0.036 mole of diethylaminoethyl chloride hydrochloride used instead of chloroacetic acid.

The details of the products synthesized according to Examples 1 to 50 are summarized in Tables 1 and 2, in which the values of the specific optical rotation [ α ] (measured at λ = 220 nm) of the 1% solutions are also given. These can be evaluated by Fig. 2, where the [ α ] values (measured at λ = 220 nm) of the 1% solutions made with different weight ratios from β- cyclodextrin (1), or from one made with epichlorohydrin Cyclodextrin polymer (2), or from a carboxymethyl- β- cyclodextrin (3) coupled with butylene diglycidyl ether and gelatin can be seen. If one compares these values with the data recorded in the tables of the specific optical turning capacity of the products having the cyclodextrin ratios corresponding to the examples, it can be confirmed that the [ α ] values of the products produced according to the invention are, without exception, more positive, ie, themselves the reaction between the starting substances took place and a polymer was formed in which gelatin also represents a component.

Table 1

Information relating to Examples 1 to 34 (reagents calculated for 1 g of gelatin)

Table 2

Information relating to Examples 35 to 50 (reagents calculated for 1 mmol β- cyclodextrin)

Claims (7)

1. A process for the preparation of gelatin / cyclodextrin copolymers, characterized in that

• a) 1.5 to 15 mmol of epichlorohydrin or 0.1 to 2.5 mmol of diglycidyl ether of the formula (I) or a coupling agent of the general formula (II) or (III) - optionally an initiator when using (III) - and 0.05 to 3.0 mmol of cyclodextrin or substituted cyclodextrin of the general formula (IV) CD- (OQX) _m (IV) or 0.1 to 20 g of water-soluble cyclodextrin polymer general formula (V) reacted with 1 g gelatin, or
• b) 0.2 to 2.0 mmol of the compound of the general formula (VI) or (VII) or (VIII) X ′ - (CH₂) _m -COOH (VI)
  H₂N- (CH₂) _m -COOH (VII)
  R₂ = N-R⁶ (VIII) further 0.03 to 3.5 g of gelatin and 5 to 15 mmol of epichlorohydrin or 1.0 to 5.0 mmol of diglycidyl ether of the formula (I) or a coupling agent of the general formula (II) or ( III) - optionally an initiator when using (III) - with 1 mmol of cyclodextrin, in which R is hydrogen or a C _1-5 alkyl group in the above formulas;
  Y chlorine, bromine, NH₂ or C _1-4 alkoxy, e.g. B. methoxy, ethoxy, n or isopropoxy group;
  Q is a - (CH₂) _m group;
  X is hydrogen or CO₂H, NH₂, NR², OH or SO₃H group;
  R1 is a bridge coupling the cyclodextrin molecules in the polymer chain through an ether linkage, the constituent of which is the coupling agent;
  R² is hydrogen or a substituent identical to R³;
  R³ is an OH, -CD · a R⁴, OR⁵, O (CH₂) _m OR⁵, (OCH₂CH₂) _m OR⁵, NR², -NH (CH₂) _m -CO₂H group;
  R⁴-R¹ · R², or a substituent identical to R⁵;
  R⁵ is hydrogen or - (CH₂) _m -CO₂H, H₂N- (CH₂) _m group;
  R⁶ is hydrogen or - (CH₂) _m -Cl or - (CH₂) _m Br group;
  X, chlorine or bromine;
  CD is an α, β or γ cyclodextrin molecule;
  a is an integer from zero to a value one unit lower than the original number of hydroxyl groups of the cyclodextrin;
  m is a number from 1 to 6;
  n is a number from 2 to 12; and
  p zero or a number which is at least two units lower than the original number of hydroxyl groups of the cyclodextrin,

mean, and then the by-products of the reaction and that Water removed in both procedures if necessary. 2. The method according to claim 1, characterized characterized in that by means of the lime process manufactured gelatin with a low isoelectric Dot and cyclodextrin, or a substituted cyclodextrin of the general formula (IV) used as starting substances. 3. The method according to claim 1, characterized characterized in that by means of the lime process manufactured gelatin with a low isoelectric point and a water soluble cyclodextrin polymer of the general Formula (V) used as starting substances. 4. The method according to claim 1, characterized characterized in that by means of the acid process  made gelatin with a high isoelectric point and cyclodextrin, or a substituted cyclodextrin general formula (IV) used as starting substances. 5. The method according to claim 1, characterized characterized in that by means of the acid process made gelatin with a high isoelectric point and a water soluble cyclodextrin polymer of the general Formula (V) used as starting substances. 6. Gelatin / cyclodextrin copolymers available according to one of the methods according to claims 1 to 5.