WO2001053359A1

WO2001053359A1 - Crosslinked water insoluble gel from non-hydrolyzed water soluble polymers

Info

Publication number: WO2001053359A1
Application number: PCT/US2001/001448
Authority: WO
Inventors: Jenn S. Shih
Original assignee: Isp Investments Inc.
Priority date: 2000-01-18
Filing date: 2001-01-12
Publication date: 2001-07-26
Also published as: AU2001229523A1

Abstract

A crosslinked water insoluble gel derived from water soluble polymers consisting essentially of poly(ethyleneimine) and a non-hydrolyzed cyclic N-vinyl lactam polymer containing 4 to 6 ring carbon atoms in its cyclic sturcture; said gel having repeating units of formula (1) wherein W and Y are each individually C1 to C4 alkyl; subscripts x and z each have a value of from 0 to 2 and n has a value of from 0 to 100,000.

Description

CROSSLINKED WATER INSOLUBLE GEL FROM NON-HYDROLYZEP WATER SOLUBLE POLYMERS

FIELD OF THE INVENTION The present invention concerns water insoluble crosslinked polymer gel coatings or adhesive matrices for active biological, agrochemical, pharmaceutical and personal care components employed to contact animal and plant tissue or to treat an inanimate substrate. In one aspect, the present gels provide water insoluble coatings on paper, wood, glass, mineral and metal surfaces. In another aspect, the present gels provide a durable adhesive base for active biocidal, herbicidal and plant growth regulating components. In still another aspect instant gels can be employed as non- toxic, adhesive matrices for controlled release of active skin and hair care components. Further, these gels are compatible with both acidic and basic components and are thus suitably employed as thickeners, hydrogels or viscosity modifiers in many treatment formulations.

DEFINITIONS OF TERMS USED HEREIN

Poly(ethyleneimine) is a poiyfunctional amine crosslinking agent referred to as PEI;

Poly(N-vinyl pyrrolidone) having a K value of from 10 to 120 is designated as PVP;

Poly(N-vinyl lactam), referred to herein as PVL, is a cyclic amide having from 4 to 6 ring carbon atoms which optionally can be substituted with lower alkyl;

Poly(N-vinyl caprolactam) is referred to as PVCL having a K value of from 10 to 120 and

N-vinylpyrrolidone and N-caprolactam are referred to as VP and VCL respectively. BACKGROUND OF THE INVENTION

Water insoluble, ampholitic salts of hydrolyzed PVP and PEI are known and described in U.S. Patent No. 5,306,504 to Lorenz. Although these salts have uses similar to those described herein, they are effective over a restricted pH range of from 7 to 12. Additionally these salts have a limited PEI concentration in the crosslinked product, i.e. between 2.5 and 6.5 wt.%. Because of the ring opening required to form patentee's salt, the hydrolyzed PVP component is prone to crosslink with itself before reacting with PEI. Hence a non-uniform distribution of the PEI crosslinking agent in the water insoluble product results.

Accordingly it is an object of this invention to overcome the above disadvantages and to provide a water insoluble, crosslinked polymer which is compatible with acidic and basic active components, is stable over an extended pH range and which can accommodate significantly higher concentrations of PEI in a crosslinked product wherein the distribution of the PEI in the product is substantially uniform and its concentration can be predetermined and controlled.

Another object of this invention is to provide a water insoluble matrix for a disinfectant suitably employed in an adhesive wound dressing, ostomy or denture attachment.

Another object is to provide a deformation resistant, water insoluble film coating or cushioning pad on a substrate surface wherein the firmness of the coating or padding can be adapted to meet individual needs of the consumer.

Still another object is to provide a water insoluble, adhesive gel matrix for an electron conducting agent useful in attachment to electrodes. Yet another object is to supply a water resistant matrix for cosmetically active agents which can be incorporated in the gel or a gel composition as an individual active agent or as an active agent in a formulation.

These and other objects and advantages of the present invention will become apparent from the following description and disclosure.

SUMMARY OF THE INVENTION

In accordance with the present invention there is provided a stable, water insoluble, crosslinked polymer of PEI and a PVL optionally substituted on the ring with Ci to C₄ alkyl; said crosslinked polymer defined by the formula:

wherein W and Y are each independently Ci to C alkyl; subscripts x and z each have a value of from 0 to 2 and n has a value of 0 to 100,000.

DETAILED DESCRIPTION OF THE INVENTION

The crosslinked, water insoluble gel adhesive described herein is prepared by reacting polyfunctional PEI in an aqueous mixture of base and non-hydrolyzed cyclic PVL. The PVL reactant is PVP or PVCL which are option-ally substituted on their respective rings with lower alkyl and mixtures of said PVP and PVCL. Each of the lactam reactants can be a polymer containing up to 20 wt.% non-acidic comonomer, such as for example a (meth) acrylate, (meth)acrylamide, styrene and the like. The K value of the PVL is within the range of from 10 to 120, preferably from 25 to 65. Of the PVL reactants employed herein, unsubstituted PVP, PVCL and PVP/PVCL 40/60-60/40 mixtures and VP/VCL copolymers are preferred.

A critical factor in the present invention for inhibiting hydrolysis and ring opening of the cyclic lactam component is the solubilization of the PVL in a basic solution prior to contact with PEI. Accordingly, the PVL is intimately premixed with an aqueous solution containing base sufficient to adjust the pH of the cyclic component to above 7, preferably above 7.5, before contacting with PEI. Additional amounts of base can be added during crosslinking when needed to maintain a basic reaction medium until the crosslinked product is formed. Thereafter, a base or acid can be added to the product so as to provide a pH meeting the specification commensurate with its ultimate use. When used as a water insoluble adhesive applied to the skin or hair, a pH of from about 6.5 to 7.5 is desirable; most preferably a neutral pH is preferred. For other end uses, the pH of the crosslinked gel can have a pH of from about 3.5 to 14 without sacrifice to stability of the crosslinked gel. Accordingly, pH sensitivity normally associated with PVP/PEI ampholyte salts is overcome.

The crosslinking reaction is carried out in aqueous medium at ambient temperature, e.g. below about 32°C, preferably at a temperature between about 18° and about 25°C during which the polymeric reactants are intimately mixed for a period of from about 3 to 60 minutes. Alternatively, the water insoluble, pliant films of the present crosslinked polymer can be formed directly on a substrate by coating the substrate surface with the basic aqueous PVL and PEI mixture and allowing the crosslinking to proceed on the surface. The coated surface is then dried at elevated temperature.

The aqueous mixture in the reaction zone contains between about 1 and about 70 wt.% solids, preferably between about 10 and about 30 wt.% solids. The mole ratio of reactant PEI to PVL in the reaction mixture can vary widely and can be controlled between about 1 :5 and about 1 :70, depending upon the firmness desired in the crosslinked product; higher concentrations of PEI providing a firmer, less distortable product.

Suitable bases conveniently employed for the PVL premixture include inorganic types such as sodium, potassium and ammonium hydroxides and organic types such as triethanolamine, triethylamine, 2-amino-2-methyl-1- propanol and the like and mixtures of the foregoing bases.

To increase tack in the water insoluble product, a minor amount of plasticizer, between about 5 and about 20 wt.%, based on total polymers, can be introduced into the reaction mixture. Suitable plasticizers include gums, glycerine, polyvinyl alcohols, polyethylene- or polypropylene- glycols, etc. The plasticizer can be introduced in the aqueous PVL premixture or in the resulting basic PVL/PEI mixture before, during or after the crosslinking reaction.

Other excipients can be added to the present reaction mixture or gel product. Accordingly up about 15 wt.% of an electrolyte salt such as potassium-, sodium- or magnesium- chloride or acetate can be added for conductive properties in the adhesive gel.

In the crosslinked, water insoluble gel of this invention, the PEI ampholytic salt formation resulting from the proton transfer reaction between the amine group of the imine and the carboxyl group of the ring opened PVP described by Lorenz in the '504 patent [supra] is replaced with a hydrogen bonding linkage between an amine group of the imine and the cyclic amide of the non-hydrolyzed PVL. Accordingly, the structure of the present crosslinked polymer is distinguished from that of the patent. Advantageously, the PEI concentration in the present crosslinked polymer, which is not dependent on a few random ring opened reaction sites, can be significantly extended to between about 1 :5 to 1 :70 part PEI to parts PVL. Additionally, the increased number of available crosslinkable sites not only provides for more uniform distribution of the PEI throughout the polymer product but also allows adjustment of physical properties in the product. For example, PEI concentrations at or closely approaching 1 :5 in the present product produces a moldable gel. The higher concentrations of PEI, up to about 1:12, produce a firmer, water insoluble adhesive gel. At lower concentrations of PEI, e.g. preferably between about 1 :15 and 1 :45, the crosslinked product fulfills all of the cosmetic, antiseptic, pharmaceutical applications disclosed for the product described in U.S. Patent 5,306,504, which teaching concerning uses is incorporated herein by reference.

The present crosslinked polymer has a weight average molecular weight between 10,000 and 2,000,000, preferably between 50,000 and 800,000. This polymer possesses compatibility with a broad spectrum of chemicals and can be combined with electrolytes to provide adhesive conductive gels for electrodes and for use in electron beam technology. Additionally, because of the hydrogen bonding capability of unreacted sites along the PEI chain, instant crosslinked gels affords higher loading of hydrogen bondable drugs and other similarly bondable active components. The hydrogen bonding of such active materials promotes controlled release of the active component over extended time periods. Further, since the present gel is not formed as an ampholytic salt, it is stable over a significantly broader pH range, including a range from about 3 to about 14. The above and many other uses and advantages of the present water insoluble gel are also within the scope of this invention.

Having generally described the invention, reference is now had to the following examples which represent preferred embodiments but are not to be construed as limiting to the scope of the invention as more properly defined by the appended claims. EXAMPLE 1

A mixture of 2 g of non-hydrolyzed PVP K-30 in 8 g of distilled water containing 0.5 g of 10% sodium hydroxide and having a pH of 9.2 was contacted in a glass test tube with 0.5 g of 10% PEI in water under agitation at room temperature. The concentration of water in the reaction mixture was 80 wt.% (~ 20% solids) and the PEI to PVP weight ratio was 1 :40. The resulting mixture was allowed to stand for 20 minutes during which period a stable, water insoluble, crosslinked PVP/PEI gel was formed.

EXAMPLE 2

The reaction described in Example 1 was repeated except that PVP K- 60 adjusted to a pH of 8.0 and only 0.3 g of 10% PEI in water was substituted for PVP K-30 at pH 9.2 and 0.5 g PEI. The weight ratio of PEI to PVP in this example is 1 :66.6. After shaking for about 3 minutes, the stable, water insoluble, crosslinked gel was immediately formed.

EXAMPLE 3

A conducting, water insoluble gel was prepared in a 4 ounce glass jar by charging 35 g of non-hydrolyzed 21 % PVP K-60 in water having a pH above 7, 2.5 g magnesium acetate and 12.5 g of PEG 300 and mixing with a homogenizer. To the homogenized mixture, 1.0 g of 10% PEI in water was added dropwise over a period of about 5 minutes while stirring to provide a mole ratio of PEI to PVP of 1 :73.5. After about 10 minutes, a stable, water insoluble gel was formed having a conductance of 3700 mho. EXAMPLE 4

A water insoluble gel coating was formed by combining in a 20 ml test tube the reaction mixture of Example 1. After about 2 minutes mixing, this solution was cast on a 2 mil thick Mylar film and dried in an oven at 80°C. The resulting gel coating was water insoluble and dye receptive and was printed with a color printer.

EXAMPLE 5

Example 1 was repeated, except that PVCL K-40 was substituted for PVP K-30 and 0.7 g of 10% sodium hydroxide was substituted for 0.5 g of 10% NaOH to provide a 20% aqueous solution having a pH of 11.4. After shaking and standing for 5 minutes, a stable, water insoluble gel was formed.

EXAMPLE 6

Example 1 was repeated except that K-40 poly(N-vinyl pyrrolidone/N- vinyl caprolactam) (wt. ratio 50/50 copolymer) was substituted for PVP K-30 and 0.6 g of 10% NaOH was added to produce a 20% solution of the lactam copolymer having a pH of 10.0. After adding and shaking with the PEI crosslinking agent, the stable, water insoluble gel formed within 5 minutes.

EXAMPLE 7

Example 1 was repeated except that a K-60 mixture of PVP and PVCL was substituted for K-30 PVP. About 0.6 g of 10% NaOH was added to the mixture to produce a 20% solution of the PVL mixture having a pH of 9.5. After adding PEI crosslinking agent and shaking for about 5 minutes, a stable, water-insoluble gel was formed. EXAMPLE 8

To the reaction mixture of Example 2, prior to the addition of PEI, was added 2 g of glycerin and the resulting mixture at about 20°C crosslinked within a period of 5 minutes. This product possessed increased tackiness without diminishing the stability of the gel product.

EXAMPLE 9

In Example 1 , 2.5 g of potassium chloride was added to the PVP K-30 aqueous component prior to contact with PEI. Crosslinking of the PVP mixture ensued about 6 minutes after PEI addition at a temperature of about 25°C. The resulting crosslinked product possessed good conductivity suitable for use involving electrodes.

EXAMPLE 10

In Example 1 , 0.5 g of a pesticide, sodium N-methyl dithiocarbamate - 2-chloroethyl trimethyl ammonium chloride, is added to the PVP prior to contact with PEI and the water insoluble gel of the invention formed after addition of PEI is sprayed as an aqueous suspension on a plant the pesticide is retained on the plant with substantially no seepage to ground water after rain or watering.

This example can be repeated using other pesticides such as diammonium ethylene bis(dithiocarbamate), ammonium sulfamate etc. with the same result. Example 10 is repeated, except that an antimicrobial agent, benzyl dimethyl-2-phenoxy-ethyl-ammonium-3-hydroxy-2-naphthoate, is substituted for the pesticide. The resulting aqueous suspension is sprayed on a wound or wound dressing. Other antimicrobial agents such as for example cetyl trimethyl ammonium bromide, can be substituted herein for the same affect.

EXAMPLE 11

The reaction mixture of Example 3 is coated to a 0.5 mil thickness on a 1.5 mil Mylar film and then dried at elevated temperature at about 45°C. An adhesive water insoluble surface on the Mylar film is obtained.

This example can be repeated using a paper substrate in place of Mylar.

EXAMPLE 12

Example 1 was repeated except that 2 g of 10% PEI in water was substituted to provide a weight ratio of PEI/PVP of 1 :10 an the water insoluble gel was formed.

It is to be understood that many other applications for the present water insoluble gels are also included within the scope of the invention, for example PVCL homopolymer, as well as PVP/PVCL copolymers in different monomer proportions can be substituted in Example 1 to provide similar water insoluble gels.

Claims

WHAT IS CLAIMED IS:

1. A crosslinked, water insoluble gel having repeating units of

wherein W and Y are each individually lower alkyl; subscripts x and z each have a value of from 0 to 2 and n has a value of from 0 to 100,000.

2. The gel of claim 1 wherein x and z are zero.

3. The gel of claim 1 wherein n has a value of from 100 to 5,000.

4. The gel of claim 1 which is derived from a cyclic, non-hydrolyzed lactam polymer selected from the group consisting of PVP, PVCL, VP/VCL copolymers having a K-value of from 10 to 120, either or both of VP or VCL polymers optionally containing up to 20 wt.% of a non-acidic comonomer, and mixtures of the foregoing; which lactam polymer, at a pH above 7, is crosslinked with PEI in aqueous solution.

5. The vinyl lactam polymers of claim 4 having a K value of from 25-65.

6. A skin adhesive, water insoluble gel composition comprising an effective ameliorating amount of an active personal care component and the gel of one of claims 1 , 2, 3, 4 or 5.

7. A conductive, water insoluble gel composition comprising the water insoluble gel of one of claims 1, 2, 3, 4 or 5 and an effective conducting amount of an electrolyte.

8. A substrate having a surface coated with an effective water resisting amount of the gel of one of claims 1 , 2, 3, 4 or 5; said gel being dried on the substrate surface.

9. The coating of claim 8 wherein said substrate is a wound dressing.

10. The coating of claim 8 wherein said substrate is paper.

11. The process for the preparation of the gel of claim 1 which comprises:

(a) dissolving a cyclic lactam polymer having repeating units of

and a K value of from 10 to 120; wherein W is Ci to C₄ alkyl or a mixture thereof and x is an integer having a value of from 0 to 2, in water at a pH above 7 which optionally can be adjusted with a base;

(b) introducing an effective crosslinking amount of PEI to the water solution of (a) at ambient temperature during agitation;

(c) allowing the resulting reaction mixture to crosslink over a period of from about 3 to about 60 minutes and

(d) recovering the crosslinked gel product of claim 1 as the product of the process.

12. The process of claim 11 wherein said lactam is PVP or PVCL has a K-value of 10-120.

13. The process of claim 12 wherein the K-value of said PVP or PVCL is 25-65.

14. The process of claim 10 wherein the weight ratio of said PVP/PVCL mixture is between about 40:60 and 60:40.

15. The process of claim 10 wherein the aqueous reaction media contains between about 5 and about 60 wt.% solids.

16. The process of claim 15 wherein the aqueous reaction media contains between about 10 and about 30% solids.

17. The process of claim 10 wherein said lactam polymer is selected from the group consisting of PVP, PVCL, a PVP/PVCL copolymer, a PVP and/or a PVCL copolymer optionally containing lower alkyl ring substitution and containing 0 to 20 wt.% of a non-acidic comonomer.

18. The process of claim 17 wherein said lactam polymer is selected from the group consisting of unsubstituited PVP, PVCL , PVP/PVCL copolymers and PVP/PVCL mixtures.