Description:1
FORM-2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE
SPECIFICATION
(See section 10 and rule 13)
NOVEL NANOSTRUCTURED TOPICAL FORMULATIONS OF RETINOIDS
G D Goenka University, an Indian university of Sohna Gurugram Road, Sohna, Haryana, India, 122103
THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED
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FIELD OF INVENTION:
The present invention relates to pharmaceutical science field, which aims at design and development of novel nanostructured topical formulations of retinoids.
BACK GROUND:
BCCs were the most common kind of unresponsive tumour, and they were distinguished by the upregulation of p53 and cellular retinol-binding protein-1 compared to undifferentiated tumours. Acne vulgaris is a common inflammatory skin condition treated using Tretinoin-loaded Curcumin (TRT-CUR), Tazatorene loaded Curcumin (TZT-CUR) nanoemulsion.
No attempt has been done earlier as combinatorial approach for Curcumin and Tretinion. However, some individual studies have been carried out as described following:
Yin W et al., demonstrate topical application of tretinoin ointment (atRA as the active ingredient) effectively inhibited B16F10 melanoma growth. This is accompanied by markedly enhanced CD8+ T-cell responses, as evidenced by significantly increased proportions of effector CD8+ T cells expressing granzyme B, tumour necrosis factor-a, or interferon-?, and Ki67+ proliferating CD8+ T cells in atRA-treated tumours compared with vaseline controls. Furthermore, topical atRA treatment promoted the differentiation of effector CD8+ T cells in draining lymph nodes (DLN) of tumour-bearing mice. Interestingly, atRA did not affect tumoral CD4+ T-cell response, and even inhibited the differentiation of interferon-?-expressing T helper type 1 cells in DLN. Importantly, we demonstrated that the tumour-inhibitory effect of atRA was partly dependent on CD8+ T cells, as CD8+ T-cell depletion restored tumour volumes in atRA-treated mice, which, however, was still significantly smaller than those in vaseline-
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treated mice. Finally, we demonstrated that atRA up-regulated MHCI expression in B16F10 cells, and DLN cells from tumour-bearing mice had a significantly higher killing rate when culturing with atRA-treated B16F10 cells. Hence, our study demonstrates that topical atRA treatment effectively inhibits melanoma growth partly by promoting the differentiation and the cytotoxic function of effector CD8+ T cells.
Anuchapreeda S. et al. developed a new formulation of a curcumin lipid nanoemulsion having the smallest particle size, the highest loading, and a good physical stability for cancer chemotherapy. Curcumin lipid nanoemulsions were prepared by a modified thin-film hydration method followed by sonication. Soybean oil, hydrogenated L-a-phosphatidylcholine from egg yolk, and cosurfactants were used to formulate the emulsions. The resultant nanoemulsions showed mean particle diameter of 47–55 nm, could incorporate 23–28 mg curcumin per 30 mL, and were stable in particle size for 60 days at 4°C. The cytotoxicity studies of curucumin solution and curcumin-loaded nanoemulsion using B16F10 and leukemic cell lines showed IC50 values ranging from 3.5 to 30.1 and 22.2 to 53.7 µM, respectively. These results demonstrated the successful incorporation of curcumin into lipid nanoemulsion particles with small particle size, high loading capacity, good physical stability, and preserved cytotoxicity.
The Box-Behnken design was employed based on the statistical data analysis with the amount of oil (10-15 %), surfactant (10-15%), and cosurfactant (25-30%). Nanoemulsion is a promising alternative to increase drug delivery system penetration and target poorly soluble drugs by increasing its absorption through the skin, the better retention time of drug in the target area and eventually result in lesser side effects. Oleic acid, tween 80, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, on the basis of various screening tests.
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TRT- CUR-NEG was used to investigate the in vitro cytotoxic effect of Test Items in a murine melanoma (B16F10) cells. Cells were treated with Test Items for 72 h and the cytotoxic effect was determined by MTT assay. The % cytotoxicity w.r.t to control exhibited 33.7%. Results demonstrated that TRT-CUR-NEG exhibited a better cytotoxic profile in murine melanoma cells with an IC50 of 0.56 mg/mL and % cytotoxicity w.r.t to control exhibited 74.6%
OBJECTIVE OF THE INVENTION:
1. It is an object of the invention to provide a novel nanostructured topical formulation of retinoids against Basal Cell Carcinoma comprising drug-loaded Curcumin nanoemulsion, oil (10-15 %), surfactant (10-15%), and cosurfactant (25-30%).
2. It is an object of the invention to provide a novel nanostructured topical formulation of retinoids against Basal Cell Carcinoma comprising Curcumin nanoemulsion is Tretinoin-loaded Curcumin (TRT-CUR) or Tazatorene loaded Curcumin (TZT-CUR) nanoemulsion, oil (10-15 %), surfactant (10-15%), and cosurfactant (25-30%).
SUMMARY
BCCs were the most common kind of unresponsive tumour, and they were distinguished by the upregulation of p53 and cellular retinol-binding protein-1 compared to undifferentiated tumours. Acne vulgaris is a common inflammatory skin condition treated using Tretinoin-loaded Curcumin (TRT-CUR), Tazatorene loaded Curcumin (TZT-CUR) nanoemulsion. The Box-Behnken design was employed based on the statistical data analysis with the amount of oil (10-15 %), surfactant (10-15%), and cosurfactant (25-30%). Nanoemulsion is a promising alternative to increase drug delivery system penetration and target poorly soluble drugs by increasing its absorption through the skin, the better retention time of drug in the target area and eventually result in lesser side effects. Oleic acid, tween 80, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, on the basis of various screening tests. TRT- CUR-NEG was used to investigate the in vitro cytotoxic effect of Test Items in a murine melanoma (B16F10) cells. Cells were treated with Test
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Items for 72 h and the cytotoxic effect was determined by MTT assay. The % cytotoxicity w.r.t to control exhibited 33.7%. Results demonstrated that TRT-CUR-NEG exhibited a better cytotoxic profile in murine melanoma cells with an IC50 of 0.56 mg/mL and % cytotoxicity w.r.t to control exhibited 74.6%.
DETAILED DESCRIPTION:
For the purpose of promoting an understanding of the principles of the invention, reference will now be made to the embodiment illustrated in the figures and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended, such alterations and further modifications in the illustrated system, and such further applications of the principles of the invention as illustrated therein being contemplated as would normally occur to one skilled in the art to which the invention relates.
It will be understood by those skilled in the art that the foregoing general description and the following detailed description are exemplary and explanatory of the invention and are not intended to be restrictive thereof.
Reference throughout this specification to “an aspect”, “another aspect” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrase “in an embodiment”, “in another embodiment” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.
The terms "comprises", "comprising", or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process or method that comprises a list of steps does not include only those steps but may include other steps not expressly listed or inherent to such process or method. Similarly, one or more devices or systems or elements or structures or components proceeded by "comprises... a" does
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not, without more constraints, preclude the existence of other devices or other systems or other elements or other structures or other components or additional devices or additional systems or additional elements or additional structures or additional components.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The system, methods, and examples provided herein are illustrative only and not intended to be limiting.
The terms “a” and “an” herein do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced items.
The terms “having”, “comprising”, “including”, and variations thereof signify the presence of a component.
In one of the embodiments, with best ratio’s nanoemulsion formulated by using ultrasonication, were incorporated to nanoemulgel by using Carbopol gel for better applicability and results.
Now the present invention will be described below in detail with reference to the following embodiment.
Example 1
Preparation of novel nanostructured topical formulation of retinoids
The Box-Behnken design was employed based on the statistical data analysis with the amount of oil (10-15 %), surfactant (10-15%), and cosurfactant (25-30%). Nanoemulsion is a promising alternative to increase drug delivery system penetration and target poorly soluble drugs by increasing its absorption through the skin, the better retention time of drug in the target area and eventually result in lesser side effects. Oleic acid, tween 80,
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and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, on the basis of various screening tests.
Example 2
In vitro cytotoxic effect
TRT- CUR-NEG was used to investigate the in vitro cytotoxic effect of Test Items in a murine melanoma (B16F10) cells. Cells were treated with Test Items for 72 h and the cytotoxic effect was determined by MTT assay. The % cytotoxicity w.r.t to control exhibited 33.7%. Results demonstrated that TRT-CUR-NEG exhibited a better cytotoxic profile in murine melanoma cells with an IC50 of 0.56 mg/mL and % cytotoxicity w.r.t to control exhibited 74.6%.
Variations and modifications of the foregoing are within the scope of the present invention. Accordingly, many variations of these embodiments are envisaged within the scope of the present invention.
The foregoing descriptions of specific embodiments of the present invention have been presented for purposes of description. They are not intended to be exhaustive or to limit the present invention to the precise forms disclosed, and obviously many modifications and variations are possible in light of the above teaching.
The embodiments were chosen and described in order to best explain the principles of the present invention and its practical application, and to thereby enable others skilled in the art to best utilize the present invention and various embodiments with various modifications as are suited to the particular use contemplated. It is understood that various omissions and substitutions of equivalents are contemplated as circumstances may suggest or render expedient, but such omissions and substitutions are intended to cover the application or implementation without departing from the spirit or scope of the present invention.
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We claim,
1. A novel nanostructured topical formulation of retinoids against Basal Cell Carcinoma comprising drug-loaded Curcumin nanoemulsion, oil (10-15 %), surfactant (10-15%), and cosurfactant (25-30%).
2. The novel nanostructured topical formulation of retinoids as claimed in claim 1, wherein drug-loaded Curcumin nanoemulsion is Tretinoin-loaded Curcumin (TRT-CUR) or Tazatorene loaded Curcumin (TZT-CUR) nanoemulsion or in combinations.
3. The novel nanostructured topical formulation of retinoids as claimed in claim 1, wherein oil is oleic acid.
4. The novel nanostructured topical formulation of retinoids as claimed in claim 1, wherein surfactant is tween 80.
5. The novel nanostructured topical formulation of retinoids as claimed in claim 1, wherein co-surfactant is propylene glycol.
6. The novel nanostructured topical formulation of retinoids as claimed in claim 1, wherein said topical formulation shows 33.7% cytotoxicity effect in the case of TZT-CUR-NEG formulation and 74.6% cytotoxicity effect in TRT-CUR-NEG formulation.
Dated this 28/07/2023 G D Goenka University, Sohna Gurugram Road, Sohna, Haryana, India, 122103
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ABSTRACT
NOVEL NANOSTRUCTURED TOPICAL FORMULATIONS OF RETINOIDS
BCCs are the most common kind of unresponsive tumour, and they were distinguished by the upregulation of p53 and cellular retinol-binding protein-1 compared to undifferentiated tumours. Acne vulgaris is a common inflammatory skin condition treated using Tretinoin-loaded Curcumin (TRT-CUR), Tazatorene loaded Curcumin (TZT-CUR) nanoemulsion. The Box-Behnken design was employed based on the statistical data analysis with the amount of oil (10-15 %), surfactant (10-15%), and cosurfactant (25-30%). Oleic acid, tween 80, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, on the basis of various screening tests. TRT- CUR-NEG is used to investigate the in vitro cytotoxic effect of Test Items in a murine melanoma (B16F10) cells. Cells are treated with Test Items for 72 h and the cytotoxic effect is determined by MTT assay. The % cytotoxicity w.r.t to control exhibited 33.7%. Results demonstrated that TRT-CUR-NEG exhibited a better cytotoxic profile in murine melanoma cells with an IC50 of 0.56 mg/mL and % cytotoxicity w.r.t to control exhibited 74.6% , Claims:We claim,
1. A novel nanostructured topical formulation of retinoids against Basal Cell Carcinoma comprising drug-loaded Curcumin nanoemulsion, oil (10-15 %), surfactant (10-15%), and cosurfactant (25-30%).
2. The novel nanostructured topical formulation of retinoids as claimed in claim 1, wherein drug-loaded Curcumin nanoemulsion is Tretinoin-loaded Curcumin (TRT-CUR) or Tazatorene loaded Curcumin (TZT-CUR) nanoemulsion or in combinations.
3. The novel nanostructured topical formulation of retinoids as claimed in claim 1, wherein oil is oleic acid.
4. The novel nanostructured topical formulation of retinoids as claimed in claim 1, wherein surfactant is tween 80.
5. The novel nanostructured topical formulation of retinoids as claimed in claim 1, wherein co-surfactant is propylene glycol.
6. The novel nanostructured topical formulation of retinoids as claimed in claim 1, wherein said topical formulation shows 33.7% cytotoxicity effect in the case of TZT-CUR-NEG formulation and 74.6% cytotoxicity effect in TRT-CUR-NEG formulation.