GEL CONTAINING PIRFENIDONE

Information

  • Patent Application
  • 20240238262
  • Publication Number
    20240238262
  • Date Filed
    August 30, 2023
    a year ago
  • Date Published
    July 18, 2024
    6 months ago
Abstract
The invention relates to a gel composition containing pirfenidone, which is advantageous over other cutaneously administered pharmaceutical forms known in the prior art and which can be used in treatment for the restoration of tissues with fibrotic lesions and for the prevention of fibrotic lesions.
Description
FIELD OF INVENTION

The present invention is related to a gel formula that contains Pirfenidone, which offers advantages over other pharmaceutical forms of known cutaneous administration in the state of the technique.


BACKGROUND OF THE INVENTION

The 5-methyl-1-phenyl-2(1H)-pyridone, formula;




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It is a drug that has been applied in the restoration of tissues with lesions with fibrosis and the prevention of fibrotic lesions. This compound, Pirfenidone, it is by itself a known compound and its pharmacological effects has been described, for example, in Japanese applications numbers 87677/1974 and 1284338/1976, as an anti-inflammatory agent that includes antipyretic and analgesics. The U.S. Pat. No. 3,839,346, published Oct. 1, 1974; the U.S. Pat. No. 3,974,281, published Aug. 10, 1976; the U.S. Pat. No. 4,042,699 published Aug. 16, 1977, and the U.S. Pat. No. 4,052,509 published Oct. 4, 1977, which described the methods for the obtained Pirfenidone, as well as its use as an anti-inflammatory agent. In the Mexican patent 182, 266 the antifibrotic activity of the 5-methyl-1-phenyl-2(1H)-pyridone is described.


Different resources and treatments have been used to the date and none of them have shown to be really effective. Pirfenidone has shown its efficacy as an anti-fibrotic agent in different pathologies and organs, and has been demonstrated in previous works, where we have observed an effect on the fibroblasts and the production of collagen and extracellular matrix, as well as in experimental models and in clinical tests also.


Many substances could form gels when a gelificant agent is added. This is use in many diverse products in the manufacturing industry, from food to paint, passing through adhesives.


Gels are also important in the chemistry part related with the processes SOL_GEL and in the synthesis of solid materials with nanopores.


Gels are classified in: aqueous (hydrogels) or organic (organogels), dependingo if the aqueous component is water or an organic solvent; organic or inorganic in nature, colloidal or thick grain, according to the size of the particles; and rigid gels, elastic or tixothrophic, according to its mechanic properties.


The hydrocolloids are substances that are produced from vegetable and animal proteins or multiple sugars. They have the capacity to swell themselves and to bind to water. The hydrocolloids are used to thicken, solidify and stabilize food.


OBJECT OF THE INVENTION

The object of the present invention is to provide a gel composition for its cutaneous administration that contains Pirfenidone, a viscous agent; a solubilizer; a non ionic solubilizer; a conserving agent; a neutralizer agent and purified water.


Also, it is the object of the present invention to provide a process of manufacture of a gel that contains pirfenidone for its cutaneous application.


Another objective of the present invention is to provide a gel medicine to be used as an anti-fibrotic and anti-inflammatory agent.







SPECIFICATION OF THE INVENTION
Composition of the Gel

The composition of the gel contains from 2 to 12% of Pirfenidone is elaborated utilizing from 0.4 to 1.2% of a viscous agent, from 10 to 30% of a solubilizer, from 5 to 15% of a non ionic solubilizer, from 0.2 to 1% of a conserving agent, from 0.4 to 1.2% a neutralizer agent and the rest of purify water. The viscous agent is selected from a carbomer 940 (MR); Ultrex 10(MR), cellulose derivatives; gums; polioxameres; ethylic alcohol and propylenglycol; the conserving agent is selected from a group that consist of Diazolidinyl urea, iodopropinil-butilcarbamate; methylparabene and a mix of these compounds; the neutralizer agent is selected from a group of primary, secondary and tertiary aliphatic amines of the mono-, bi- and triethanolamine type, and of the hydroxide alkaline metals, such as sodium hydroxide.


An example of the composition of the gel is shown in the table 1:

















Component
Quantity (g)
%




















Pirfenidone
8
8



Viscous agent
0.5
0.5



Solubilizer
20
20



Non ionic solubilizer
11.5
11.5



Conserving agent
0.5
0.5



Neutralizer
0.5
0.5



Purified water up to
100
59










The gel containing Pirfenidone is manufactured as follows:

    • a) Mix 50% of the total water to be used with the viscous agent, allowing the complete humectation of the viscous agent;
    • b) Mix separately and with constant agitation the Pirfenidone with the solubilizer agent;
    • c) Dissolve separately the non ionic solubilizer agent in the 25% water to be used at 40° C., once dissolved, the 15% of the total water is added;
    • d) Add the solution from part c) to the mix from part b), agitate until the mix is homogenate.
    • e) Dilute the neutralizer agent in 10% of the total water to use, agitate until the mix is homogenate; and
    • f) Add with constant agitation and homogenate in each addition to the mix from part a) the solution from part d); the conservative and the solution from part e).


      A prepared composition according to procedure describe is shown in table 2.
















Component
Quantity (g)



















Pirfenidone
8



Carbomer
0.5



N-methylpirrolidone
20



Macrogolglycerol
11.5



Hidroxiestearate 40




Diazolidinilurea and
0.5



Iodopropinil-butilcarbamate




Triethanoalamine
0.5



Purified water up to
100












    • These compositions are shown in an example mode, but they are not limited in any level of the reach of the description of the present invention.




Claims
  • 1-6. (canceled)
  • 7. A composition of pirfenidone gel comprising: (i) pirfenidone;(ii) a viscous agent;(iii) a solubilizer;(iv) a non-ionic solubilizer;(v) a conserving agent;(vi) a neutralizer agent; and(vii) water.
  • 8. The composition of claim 7, wherein the viscous agent is selected from the group consisting of Carbomer 940®, Ultrex 10, cellulose derivatives, gums, and poloxamers.
  • 9. The composition of claim 7, wherein the viscous agent is Carbomer 940®.
  • 10. The composition of claim 7, wherein the viscous agent is Ultrex 10.
  • 11. The composition of claim 7, wherein the solubilizer is selected from the group consisting of N-methylpyrrolidone, ethyl alcohol, and propylene glycol.
  • 12. The composition of claim 7, wherein the solubilizer is N-methylpyrrolidone.
  • 13. The composition of claim 7, wherein the solubilizer is propylene glycol.
  • 14. The composition of claim 7, wherein the non-ionic solubilizer is macrogolglycerol hydroxystearate 40.
  • 15. The composition of claim 7, wherein the conserving agent is selected from the group consisting of diazolidinyl urea, iodopropynyl butylcarbamate, methylparaben, propylparaben, and combinations thereof.
  • 16. The composition of claim 7, wherein the conserving agent is diazolidinyl urea.
  • 17. The composition of claim 7, wherein the conserving agent is iodopropynyl butylcarbamate.
  • 18. The composition of claim 7, wherein the conserving agent is diazolidinyl urea and iodopropynyl butylcarbamate.
  • 19. The composition of claim 7, wherein the conserving agent is methylparaben or propylparaben.
  • 20. The composition of claim 7, wherein the neutralizer agent is selected from the group consisting of primary, secondary and tertiary aliphatic amines, mono-, bi-, and triethanolamine, and hydroxide alkaline metals.
  • 21. The composition of claim 7, wherein the neutralizer agent is triethanolamine.
  • 22. The composition of claim 7, wherein the neutralizer agent is a hydroxide alkaline metal.
  • 23. The composition of claim 7, wherein the neutralizer agent is sodium hydroxide.
  • 24. The composition of claim 7, wherein the composition comprises: (i) 2-12% pirfenidone;(ii) 0.4-1.2% of a viscous agent;(iii) 10-30% of a solubilizer;(iv) 5-15% of a non-ionic solubilizer;(v) 0.2-1% of a conserving agent;(vi) 0.4-1.2% of a neutralizer agent; and(vii) water.
  • 25. The composition of claim 7, wherein the viscous agent is Carbomer 940®, the solubilizer is N-methylpyrrolidone, the conserving agent is diazolidinyl urea and iodopropynyl butylcarbamate, and the neutralizer agent is triethanolamine.
  • 26. The composition of claim 7, wherein the composition comprises 8% pirfenidone, 0.5% of Carbomer 940®, 20% of N-methylpyrrolidone, 11.5% of the macrogolglycerol hydroxystearate 40, 0.5% of diazolidinyl urea and iodopropynyl butylcarbamate, 0.5% of triethanolamine, and 59% of water.
Priority Claims (1)
Number Date Country Kind
MX/A/2007/009796 Aug 2007 MX national
RELATED APPLICATIONS

This application is a divisional application of U.S. patent application Ser. No. 15/435,494 (allowed), filed on Feb. 17, 2017, which is a divisional application of U.S. patent application Ser. No. 13/893,626, filed on May 14, 2013, which is a divisional application of U.S. patent application Ser. No. 12/673,304, filed on Apr. 28, 2010 (now U.S. Pat. No. 8,492,412), which claims the benefit of and which is a national stage filing of International Application Serial No. PCT/MNX2008/000107, filed on Aug. 14, 2008, which claims priority to, and the benefit of, Mexican Patent Application Serial No. MX/a/2007/009796, filed on Aug. 14, 2007, the entire contents of both of which are hereby incorporated by reference.

Divisions (3)
Number Date Country
Parent 15435494 Feb 2017 US
Child 16450150 US
Parent 13893626 May 2013 US
Child 15435494 US
Parent 12673304 Apr 2010 US
Child 13893626 US
Continuations (2)
Number Date Country
Parent 17390368 Jul 2021 US
Child 18458390 US
Parent 16450150 Jun 2019 US
Child 17390368 US