Dental gel composition of papain for the atraumatic treatment of caries and method of preparing same
A papain dental gel composition is disclosed for the atraumatic treatment of caries which comprises papain with a final activity of at least 3,000 U/mg, wherein the papain is bio-encapsulated in a mixture of pH=7 buffer-C 3-6 polyol-pectin-C 2-6 alkanolamine-nonionic emulsifier, together with pharmaceutically acceptable coloring agents, preservatives and solvents. A method of preparing said papain composition is also disclosed.
1. A dental composition of papain in the form of a gel for the atraumatic treatment of caries comprising papain with a final activity of at least 3,000 U/mg, wherein the papain is bio-encapsulated in a mixture comprising all of the following ingredients:
pH=7 buffer,
a C 3-6 polyol,
pectin,
C 2 - 6 alkanolamine,
a nonionic emulsifier,
optionally a pharmaceutically acceptable coloring agent
a preservative, and
a solvent,
wherein the composition does not include chloramine.
2. The composition according to claim 1 , wherein the pH=7 buffer is selected from the group consisting of: disodium or dipotassium acid phosphate (Na 2 HPO 4 , K 2 HPO 4 )/citric acid (C 6 H 8 O 7 ), sodium chloride (NaCI)/ sodium citrate (C 6 H 5 O 7 Na 3 . 2H 2 O)/sodium hydroxide (NaOH), sodium or potassium diacid phosphate (NaH 2 PO 4 , KH 2 PO 4 )/disodium or dipotassium acid phosphate (Na 2 HPO 4 , K 2 HPO 4 ), tris-(hydroxymethyl)-aminomethane (TRIS)/hydrochloric acid (HCI).
3. The composition according to claim 1 , wherein the pH=7 buffer is KH 2 PO4/Na 2 HPO 4 .
4. The composition according to claim 1 , wherein the C 3 - 6 polyol is selected from the group consisting of: 1,2,3-propanetriol (glycerin), 1,2-propanediol (propyleneglycol), 1,3-butanediol, 1,4-butanediol, 1,3-butenediol, 2,3-butenediol, 2,2-dimethyl-1,3 propanediol (neopentylglycol), erythritol, sorbitol, mannitol, and mixtures thereof.
5. The composition according to claim 4 , wherein the C 3-6 polyol is 1,2-propanediol (propyleneglycol).
6. The composition according to claim 1 , wherein the pectin is apple bagasse pectin or citrus pectin.
7. The composition according to claim 6 , wherein the pectin employed is citrus pectin.
8. The composition according to claim 1 , wherein the C 2-6 alkanolamine is selected from the group consisting of: monoethanolamine, diethanolamine, triethanolamine and mixtures thereof.
9. The composition according to claim 8 , wherein the C 2-6 alkanolamine is triethanolamine.
10. The composition according to claim 1 , wherein the non-ionic emulsifier is selected from the group consisting of: polyoxyethylene stearate 8; polyoxyethylene stearate 40; polyoxyethylene sorbitan monolaurate 20; polyoxyethylene sorbitan monooleate 20; polyoxyethylene sorbitan monopalmitate 20; polyoxyethylene sorbitan monostearate 20; polyoxyethylene sorbitan tristearate 20; and mixtures thereof.
11. The corn position according to claim 10 , wherein the non-ionic emulsifier is polyoxyethylene sorbitan monooleate 20.
12. The composition according to claim 1 , wherein the pharmaceutically acceptable coloring agent is present and is selected from the group consisting of: methyl blue, toluidine blue, methyl green, methylene green, gentian violet, malachite green, methylene yellow, and mixtures thereof.
13. The composition according to claim 12 , wherein the pharmaceutically acceptable coloring agent is toluidine blue.
14. The composition according to claim 12 , wherein the preservative is selected from the group consisting of: methylparaben, ethylparaben, propylparaben and mixtures thereof.
15. The composition according to claim 14 , wherein the preservative is the mixture of methylparaben and propylparaben.
16. A dental composition of papain in the form of a gel for the atraumatic treatment of caries, said composition comprising papain 10.00% w/w, citrus pectin 8.00% w/w, propyleneglycol 8.00% w/w, triethanolamine 0.72% w/w, polyoxyethylene-20 sorbitan monooleate 0.50% w/w, KH 2 PO 4 0.0378% w/w, Na 2 HPO 4 0.1283%, toluidine blue (1% w/w aq. sol.) 0.09% w/w, methylparaben 0.10% w/w, propylparaben 0.05% w/w, and distilled water 72.37% w/w,
wherein the composition has a final activity of papain of at least 3000 U/mq, and
wherein the composition does not include chloramine.
17. A method of preparing the papain dental composition of claim 1 for the atraumatic treatment of caries, said method comprising:
a) adding to distilled water while stirring at approximately 1,500 rpm the components of a pH=7 buffer, one or more pharmaceutically acceptable preservatives, and finally 30,000 U/mg papain until complete dispersion to a final neutral pH (pH=7);
b) wetting pectin while stirring in a C 3-6 polyol, then adding the non-ionic emulsifier, and finally a C 2-6 alkanolamine until neutralization of the pectin acidity thus forming a neutral encapsulating emulsion (pH=7); and
c) adding the neutral encapsulating emulsion from step b) to the dispersion obtained in step a) under low speed stirring to obtain a stable gel comprising papain.
18. The method according to claim 17 , said method comprising a further step of adding under stirring, to the stable gel comprising papain, a coloring agent dissolved in a pharmaceutically acceptable solvent.
19. The method according to claim 17 , wherein the stirring in step c) is performed at between approximately 20 and approximately 150 rpm.
20. The method according to claim 17 , wherein the concentration ratio of pectin/C 3-6 polyol/C 2-6 alkanolamine employed ranges from 4/4/0.36 to 10/10/0.90 expressed in % w/w, respectively.
21. The method according to claim 20 , wherein the concentration ratio of pectin/C 3-6 polyol/C 2-6 alkanolamine is 8/8/0.72 expressed in % w/w.
22. The method according to claim 17 , said method further comprising the step of packing the obtained gel into multi-dose syringes.
23. A method of preparing the papain dental composition of claim 1 for the atraumatic treatment of caries, said method comprising:
a) adding to distilled water while stirring at approximately 1,500 rpm potassium monobasic phosphate, sodium diacid phosphate, methylparaben, propylparaben, and finally 30,000 U/mg papain until complete dispersion to a final neutral pH (pH=7);
b) wetting while stirring citrus pectin in propyleneglycol, adding polyoxyethylene sorbitan monooleate 20 , and finally triethanolamine until neutralization of the citrus pectin thus forming a neutral encapsulating emulsion (pH=7), wherein the concentration ratio of citrus pectin/propyleneglycol/triethanolamine employed ranges from 4/4/0.36 to 10/10/0.90 expressed in % w/w, respectively;
c) adding the neutral encapsulating emulsion from step b) to the dispersion obtained in step a) under low speed stirring between approximately 20 and approximately 150 rpm to obtain a stable gel of papain dispersion;
d) adding under stirring to the stable gel of papain toluidine blue as coloring agent dissolved in a pharmaceutically acceptable solvent; and
e) packing the obtained gel into multi-dose syringes.
24. The method according to claim 23 , wherein the toluidine blue coloring agent is added as a solution of 1% w/w toluidine blue dissolved in distilled water.