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WO2016108130A1 - Compositions pharmaceutiques topiques comprenant du nébivolol pour le traitement de plaies diabétiques - Google Patents

Compositions pharmaceutiques topiques comprenant du nébivolol pour le traitement de plaies diabétiques Download PDF

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Publication number
WO2016108130A1
WO2016108130A1 PCT/IB2015/059742 IB2015059742W WO2016108130A1 WO 2016108130 A1 WO2016108130 A1 WO 2016108130A1 IB 2015059742 W IB2015059742 W IB 2015059742W WO 2016108130 A1 WO2016108130 A1 WO 2016108130A1
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WO
WIPO (PCT)
Prior art keywords
nebivolol
composition
pharmaceutical composition
topical pharmaceutical
mixture
Prior art date
Application number
PCT/IB2015/059742
Other languages
English (en)
Inventor
Pankaj Da SHELAR
Jaiprakash Jaysingra BHELONDE
Lakshmi Prasad
Shahnaz AKHTAR
Vyas Madhavrao Shingatgeri
Neeta Gupta
Anil MAKWANA
Simrata Bedi
Ravi Kochhar
Original Assignee
Sun Pharmaceutical Industries Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sun Pharmaceutical Industries Limited filed Critical Sun Pharmaceutical Industries Limited
Publication of WO2016108130A1 publication Critical patent/WO2016108130A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • the present invention relates to a stable topical pharmaceutical composition of nebivolol for the treatment of diabetic wounds in a subject, wherein the time for complete wound closure (in days) after topical administration of the composition is less than or equal to that of the marketed product, becaplermin gel.
  • Diabetes mellitus is a chronic metabolic disorder that results in slow
  • Diabetic wounds are characterized by infection, ulceration, and destruction of deep tissues associated with neurological anomalies and various degrees of peripheral vascular diseases, in particular those of lower limbs which further progress into diabetic foot ulcers.
  • the diabetic foot ulcers are classified into grade 1 and grade 2 diabetic foot ulcers.
  • Grade 1 is characterized by the superficial ulceration of skin or subcutaneous tissue
  • grade 2 is characterized by ulcers extending into tendon, bone, or capsule.
  • the current treatment management strategies for diabetic wounds include antibiotics and dressings in combination with glycemic control.
  • the only approved treatment available is in the form of a topical gel of recombinant human platelet derived growth factor, Regranex ® (becaplermin gel, 0.01%), which is indicated for the treatment of diabetic foot ulcers.
  • Regranex ® recombinant human platelet derived growth factor
  • becaplermin is expensive and comes with a black box warning for an increased rate of mortality secondary to malignancy.
  • a topical delivery system is advantageous over systemic delivery because it provides high local concentrations of the drug and respite from systemic toxic effects.
  • PCT Publication No. WO 2008/093356 discloses that the topical administration of beta blockers is effective in the treatment of diabetic complications such as diabetic wounds. It also discloses that diabetes results in increased aldose reductase activity in diabetic patients which leads to diabetic complications such as diabetic wounds.
  • topical pharmaceutical compositions of nebivolol of the present invention provide accelerated wound healing of diabetic wounds.
  • nebivolol for the treatment of diabetic wounds in a subject, wherein the composition provides a more accelerated wound closure of diabetic wounds than the marketed product, becaplermin gel.
  • a first aspect of the present invention provides a stable topical pharmaceutical composition of nebivolol for the treatment of diabetic wounds in a subject, wherein the time for complete wound closure (in days) after topical administration of the composition is less than or equal to that of the marketed product, becaplermin.
  • nebivolol includes nebivolol and pharmaceutically acceptable salts thereof.
  • the pharmaceutically acceptable salts include hydrochloride, hydrobromide, phosphate, sulphate, mesylate, besylate, tosylate, fumarate, malonate, malate, succinate, lactate, glycolate, maleate, citrate, and aspartate.
  • the pharmaceutically acceptable salt is nebivolol hydrochloride.
  • Nebivolol may be present in hydrate or anhydrate forms. It may also be present in crystalline or amorphous forms.
  • the amount of nebivolol may vary from about 0.01% w/w to about 50% w/w of the pharmaceutical composition.
  • the amount of nebivolol may be present in the composition in the range of about 0.5% w/w to about 20% w/w of the composition.
  • the pharmaceutical composition of the present invention can be used for the treatment of diabetic wounds, in particular grade 1 and grade 2 diabetic foot ulcers.
  • This composition is intended to be used as an adjunct to standard wound management interventions consisting of initial complete sharp debridement and systemic treatment for wound-related infection, along with strict glycemic control.
  • the term "complete wound closure” refers to the closure of a wound that leaves no part of the wounded tissue exposed.
  • the pharmaceutical composition provides 100% re-epithelialization of the wound.
  • re-epithelialization refers to a proliferation of epithelial cells over the wound bed, providing a cover for the new granulation tissue.
  • composition of the present invention may be in the form of a cream, gel, powder, lotion, ointment, liniment, solution, suspension, paste, aerosol, or spray.
  • the pharmaceutical composition of nebivolol may be applied topically once, twice, or thrice daily for one to three weeks.
  • the topical composition is an ointment-based composition.
  • the ointment-based composition comprises paraffin.
  • the topical composition is stable when exposed to 40°C/75% RH for a period of 3 months or more. Further, it is stable at room temperature for more than 1 year. In particular, the topical composition was found to be stable when exposed to 40°C/75% RH for a period of 6 months.
  • the pH of the topical composition is less than 8.
  • the pH of the topical composition is between 2.0 and 7.0.
  • the topical pharmaceutical composition further comprises pharmaceutically acceptable excipients selected from the group comprising viscosity enhancers, emollients, surfactants, preservatives, chelating agents, anti-oxidants, pH-adjusting agents, solvents, co-solvents, vehicles, and mixtures thereof.
  • pharmaceutically acceptable excipients selected from the group comprising viscosity enhancers, emollients, surfactants, preservatives, chelating agents, anti-oxidants, pH-adjusting agents, solvents, co-solvents, vehicles, and mixtures thereof.
  • a second aspect of the present invention provides a stable topical pharmaceutical composition of nebivolol for the treatment of diabetic wounds in a subject, wherein the pharmaceutical composition is prepared by a process comprising:
  • step ii) mixing other pharmaceutically acceptable excipients with the drug dispersion of step i) to obtain a mixture;
  • iii) optionally, melting the mixture of step ii) to obtain a molten mixture; iv) mixing the mixture of ii) or the molten mixture of step iii) with a vehicle to obtain the desired composition; and
  • step iv) filling the composition of step iv) into a suitable sized container.
  • Suitable viscosity enhancers are selected from the group comprising soft paraffin, aluminum stearate, hydroxyethyl cellulose, hydroxypropyl cellulose,
  • hydroxypropylmethyl cellulose cross-linked polyacrylate polymer, e.g., Carbomer 980, glyceryl behenate, povidone, wool-fat, hydrogenated lanolin, beeswax, white wax, and mixtures thereof. These may be present in the composition in the range of about 0.1% w/w to about 40% w/w of the composition.
  • Suitable emollients are selected from the group comprising isopropyl myristate, medium chain triglycerides, myristic acid, palmitic acid, glyceryl linoleate,
  • cyclomethicone dimethicone, decyl oleate, stearic acid, and mixtures thereof. These may be present in the composition in the range of about 1% w/w to about 50% w/w of the composition.
  • Suitable surfactants are selected from the group comprising sorbitan monostearate, polyoxythylene sorbitan monostearate, e.g., Polysorbate 60 or Polysorbate 80, non- ethoxylated glyceryl monostearate, cetomacrogol, cetostearyl alcohol, cetearyl alcohol, sodium stearoyl lactylate, lecithin, and mixtures thereof. These may be present in the composition in the range of about 0.1% w/w to about 20% w/w of the composition.
  • Suitable preservatives are selected from the group comprising methyl paraben, propyl paraben, benzyl alcohol, benzoic acid, sodium benzoate, chlorocresol, sorbic acid and its salts, phenylethyl alcohol, and mixtures thereof. These may be present in the composition in the range of about 0.01% w/w to about 5% w/w of the composition.
  • Suitable chelating agents are selected from the group comprising dimercaprol, ethylene diamine tetra acetic acid (EDTA), ethylene glycol tetra acetic acid, deferoxamine, alfa lipoic acid, and mixtures thereof. These may be present in the composition in the range of about 0.01% w/w to about 10% w/w of the composition.
  • Suitable antioxidants are selected from the group comprising sodium metabisulfite, butylated hydroxy toluene, butylated hydroxy anisole, propyl gallate, ethyl gallate, methyl gallate, ascorbic acid, tocopherol, and mixtures thereof. These may be present in the composition in the range of about 0.01% w/w to about 10% w/w of the composition.
  • Suitable pH-adjusting agents are selected from the group comprising citric acid, sodium citrate, acetic acid, sodium acetate, phosphoric acid, disodium orthophosphate, borax, sodium hydroxide, and sodium phosphate. These may be present in the composition in the range of about 0.01% w/w to about 10% w/w of the composition.
  • Suitable solvents are selected from the group comprising ethyl alcohol, isopropyl alcohol, acetone, and mixtures thereof. These may be present in the composition in the range of about 0.01% w/w to about 50% w/w of the composition.
  • Suitable co-solvents are selected from the group comprising heavy liquid paraffin, water, propylene glycol, and various grades of polyethylene glycols, e.g., polyethylene glycol 400. These may be present in the range of about 20% w/w to about 80% w/w of the composition.
  • Suitable vehicles are selected from the group comprising white soft paraffin, polyethylene glycol, purified water, and mixtures thereof. These may be present in the range of about 40% w/w to about 80% w/w of the composition.
  • butylated hydroxy toluene, and butylated hydroxy anisole were heated and then cooled to obtain a melted mixture.
  • Nebivolol hydrochloride was dispersed into heavy liquid paraffin to obtain a
  • step 3 The dispersion of step 2 was mixed with the melted mixture of step 1.
  • step 3 The mixture of step 3 was mixed with the remaining white soft paraffin to obtain an ointment.
  • step 4 The ointment of step 4 was packed into suitable sized tubes.
  • compositions comprising nebivolol in strengths of 10.00% w/w and 20.00% w/w of the composition were also prepared according to the procedure described above.
  • Irritation potential of the composition of the present invention was compared with placebo in a single dose dermal irritation study.
  • a total of 7 young adult healthy male New Zealand White Rabbits (six rabbits for Example 1 and one rabbit for placebo) were used in this study. The fur of the rabbits was removed and 4 sites (2 treated and 2 untreated test sites) were identified. The skin was abraded (only on treated test sites) with a sterile needle 18 to 24 hours prior to the application of the composition of Example 1 and the placebo.
  • 500 mg each of the composition of Example 1 and placebo was applied directly to the designated treated test sites created on either the right or left dorso-lateral trunk of the rabbits, each having a surface area of approximately 6 cm 2 .
  • the site was then covered with a gauze patch which was held in place with the help of cotton crepe bandage. For the untreated test sites, only the gauze patch was applied.
  • the time taken for the complete wound closure and percent re-epithelialization was studied in Wistar rats.
  • the rats were distributed into 5 groups: the non-diabetic control rats (group 1), diabetic control rats (group 2), placebo for Example 1 (group 3), Regranex ® (group 4), and Example 1 (group 5).
  • the complete wound closure study consisted of 7 rats in each group, while the percent re-epithelialization study consisted of 5 rats in each group.
  • the rats were anaesthetized by administering an intraperitoneal injection of a mixture of xylazine (dose 5 mg/kg body weight) and ketamine (dose 40 mg/kg body weight) which was prepared in sterile water for injection.
  • a circular area (approximately 15 mm diameter) was marked on the shaved dorsal thoracic region.
  • a full skin thickness wound was created by removing the entire skin layer from the marked area with sterile surgical scissors and forceps. The day of wound creation was considered as day 0.
  • compositions were applied twice daily in groups 3, 4, and 5 with the help of a sterile stainless steel spatula.
  • the marketed formulation Regranex ® (becaplermin 0.01% gel) has been used as a reference standard.
  • the time (in days) for wound closure was recorded.
  • a histomorphometric analysis was carried out to determine the percent of re-epithelialization on day 8 and day 15 using Leica ® QWin image analysis software.
  • Regranex gel (group 4) showed comparable results with that of the non-diabetic control (group 1) in re-epithelialization of the wound.
  • the Example 1 formulation (group 5) was found to be comparable with Regranex ® gel and the non-diabetic control in re- epithelialization and complete closure of the wound.
  • the ointments obtained from Example 1 after being packed in lami tubes, were subjected to stability testing at room temperature for a period of 14 months, and at 40°C/75% RH for a period of 6 months. The samples were analyzed to determine the amount of nebivolol, unknown impurities, and total impurities generated during the stability test.
  • Table 3 Assay of nebivolol, percentage of total unknown impurities and total impurities after subjecting the ointment of Example 1 to different stability conditions
  • composition Stability condition Assay Impurity (% w/w)
  • Example 1 (20.00%) 40°C/75% RH/6M 97.0 0.04 0.04
  • the ointments of Example 1 were found to be stable under the subjected stability conditions.
  • Hydroxyethyl cellulose was dispersed into propylene glycol to obtain a dispersion.
  • the dispersion of step 2 was mixed with the solution of step 1 to obtain a mixture.
  • Nebivolol hydrochloride and polysorbate 80 were dispersed in heated purified water to obtain a dispersion.
  • step 3 The mixture of step 3 was mixed with dispersion of step 4.
  • step 5 The mixture of step 5 was mixed with purified water to obtain a gel.
  • step 6 The gel of step 6 was packed into suitable sized tubes.
  • compositions comprising nebivolol in strengths of 2.5% w/w, 10.00% w/w, and 20.00% w/w of the composition were also prepared according to the procedure described above.
  • the pH of the compositions was found to be between 5.0 to 7.0 when subjected to stability conditions of 40°C/75% RH for a period of 1 month.
  • Butylated hydroxy toluene was added to heated polyethylene glycol 400 to obtain a molten mixture.
  • Carbomer 980 was mixed with the molten mixture of step 1.
  • Nebivolol hydrochloride was dispersed into a part of propylene glycol to obtain a drug dispersion.
  • step 3 The drug dispersion of step 3 was mixed with the mixture of step 2.
  • step 4 was mixed with the remaining part of propylene glycol to obtain a gel.
  • step 5 The gel of step 5 was packed into suitable sized tubes.
  • compositions comprising nebivolol in strengths of 2.5% w/w, 10.00% w/w, and 20.00 % w/w of the composition were also prepared according to the procedure described above.
  • step 3 The solution of step 2 and the molten mixture of step 1 were mixed to obtain a
  • Nebivolol hydrochloride was dispersed into the mixture of step 3, and purified water was added to the mixture to obtain a gel.
  • Phosphoric acid and sodium phosphate were added to the gel of step 4 to adjust the pH to between 4.0 and 7.0.
  • step 5 The gel of step 5 was packed into suitable sized tubes.
  • compositions comprising nebivolol in strengths of 5.00% w/w, 10.00% w/w, and 20.00% w/w of the composition were also prepared according to the procedure described above.
  • the gels obtained from Examples 2, 3, and 4 after being packed in lami tubes, were subjected to stability testing at 40°C/75% RH for a period of 3 month.
  • the samples were analyzed initially and after three months for determining the amount of nebivolol, unknown impurities, and total impurities generated during the stability test.
  • Table 4 Assay of nebivolol, percentage of total unknown impurities and total impurities after subjecting gels of Examples 2, 3, and 4 to different stability conditions
  • Example 2 Initial 104.70 0.03 0.03 (10%) 40°C/75% RH/3M 109.80 0.03 0.06
  • Example 2 Initial 102.50 0.02 0.02 (20%) 40°C/75% RH/3M 101.20 0.03 0.05
  • Methyl paraben was dissolved in heated purified water to obtain a solution.
  • Hydroxyethyl cellulose was dispersed into a part of propylene glycol to obtain a dispersion.
  • Nebivolol hydrochloride and benzyl alcohol were dispersed into the remaining part of propylene glycol to obtain a drug dispersion.
  • step 4 The dispersion of step 2 was mixed with the dispersion of step 3 to obtain a mixture.
  • step 4 The mixture of step 4 was mixed with purified water to obtain a gel.
  • step 5 The gel of step 5 was packed into suitable sized tubes.
  • compositions comprising nebivolol in strengths of 1.50% w/w, 3.00% w/w, and 4.50% w/w of the composition were also prepared according to the procedure described above. The pH of the compositions were found to be between 3.0 to 4.0.
  • Carbomer 980 was added to a part of propylene glycol to obtain a mixture.
  • Nebivolol hydrochloride was dispersed in the remaining part of propylene glycol to obtain a dispersion.
  • step 3 The dispersion of step 2 was mixed with mixture of step 1 to obtain a gel.
  • step 3 The gel of step 3 was packed into suitable sized tubes.
  • compositions comprising nebivolol in strengths of 1.50% w/w, 3.00% w/w, and 4.50% w/w of the composition were also prepared according to the procedure described above.
  • Cetostearyl alcohol, isopropyl myristate, polysorbate 60, and sorbitan monostearate were heated to obtain a molten mixture.
  • step 2 Methyl paraben was dissolved in heated purified water to obtain a solution. 3. The solution of step 2 and the molten mixture of step 1 were mixed to obtain a mixture.
  • Nebivolol hydrochloride and benzyl alcohol were dispersed into propylene glycol to obtain a dispersion.
  • step 4 The dispersion of step 4 was mixed with the mixture of step 3.
  • step 5 The mixture of step 5 was mixed with purified water to obtain a gel.
  • Phosphoric acid and sodium phosphate were added to the gel of step 6 to adjust the pH to between 4.0 and 7.0.
  • step 7 The gel of step 7 was packed into suitable sized tubes.
  • compositions comprising nebivolol in strengths of 1.50% w/w, 3.00% w/w, and 4.50% w/w of the composition were also prepared according to the procedure described above.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
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  • Oil, Petroleum & Natural Gas (AREA)
  • Obesity (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Abstract

La présente invention concerne une composition pharmaceutique topique stable de nébivolol pour le traitement de plaies diabétiques chez un sujet, le temps pour achever la fermeture de la plaie (en jours) après l'administration topique de la composition étant inférieur ou égal à celui du produit commercialisé, le gel bécaplermine.
PCT/IB2015/059742 2014-12-30 2015-12-17 Compositions pharmaceutiques topiques comprenant du nébivolol pour le traitement de plaies diabétiques WO2016108130A1 (fr)

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IN4000/DEL/2014 2014-12-30

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016193827A1 (fr) 2015-06-01 2016-12-08 SECRETARY, DEPARTMENT OF ELECTRONICS AND INFORMATION TECHNOLOGY (DeitY) Composition d'électrolyte pour pile à combustible à oxyde solide conductrice et son procédé de préparation
CN106727285A (zh) * 2017-01-13 2017-05-31 福元药业股份有限公司 一种软膏油脂性基质及其使用方法
WO2019166631A1 (fr) 2018-03-02 2019-09-06 Novaliq Gmbh Compositions pharmaceutiques contenant du nébivolol
US11312713B2 (en) 2017-03-10 2022-04-26 Pfizer Inc. Imidazo[4,5-C]quinoline derivatives as LRRK2 inhibitors
US11324757B2 (en) 2010-03-17 2022-05-10 Novaliq Gmbh Pharmaceutical composition for treatment of increased intraocular pressure
US11723861B2 (en) 2017-09-27 2023-08-15 Novaliq Gmbh Ophthalmic compositions comprising latanoprost for use in the treatment of ocular diseases
US12128010B2 (en) 2015-09-30 2024-10-29 Novaliq Gmbh Semifluorinated compounds and their compositions
US12226422B2 (en) 2018-04-27 2025-02-18 Novaliq Gmbh Ophthalmic compositions comprising tafluprost for the treatment of glaucoma

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US20110021526A1 (en) * 2007-01-29 2011-01-27 Vlife Science Technologies Pvt. Ltd. Pharmaceutical Composition for Treatment of Diabetic Complications
US20120329729A1 (en) * 2011-02-02 2012-12-27 University Of Southern California Methods for treating diabetic foot ulcers
US20140314711A1 (en) * 2013-03-15 2014-10-23 Genentech, Inc. IL-22 POLYPEPTIDES AND IL-22 Fc FUSION PROTEINS AND METHODS OF USE

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110021526A1 (en) * 2007-01-29 2011-01-27 Vlife Science Technologies Pvt. Ltd. Pharmaceutical Composition for Treatment of Diabetic Complications
US20120329729A1 (en) * 2011-02-02 2012-12-27 University Of Southern California Methods for treating diabetic foot ulcers
US20140314711A1 (en) * 2013-03-15 2014-10-23 Genentech, Inc. IL-22 POLYPEPTIDES AND IL-22 Fc FUSION PROTEINS AND METHODS OF USE

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Title
EMBIL, JM ET AL.: "Recombinant human platelet-derived growth factor-BB (becaplermin) for healing chronic lower extremity diabetic ulcers: an open-label clinical evaluation of efficacy", WOUND REPAIR AND REGENERATION, vol. 8, no. 3, 2000, pages 162 - 168 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11324757B2 (en) 2010-03-17 2022-05-10 Novaliq Gmbh Pharmaceutical composition for treatment of increased intraocular pressure
WO2016193827A1 (fr) 2015-06-01 2016-12-08 SECRETARY, DEPARTMENT OF ELECTRONICS AND INFORMATION TECHNOLOGY (DeitY) Composition d'électrolyte pour pile à combustible à oxyde solide conductrice et son procédé de préparation
US12128010B2 (en) 2015-09-30 2024-10-29 Novaliq Gmbh Semifluorinated compounds and their compositions
CN106727285A (zh) * 2017-01-13 2017-05-31 福元药业股份有限公司 一种软膏油脂性基质及其使用方法
US11312713B2 (en) 2017-03-10 2022-04-26 Pfizer Inc. Imidazo[4,5-C]quinoline derivatives as LRRK2 inhibitors
US11723861B2 (en) 2017-09-27 2023-08-15 Novaliq Gmbh Ophthalmic compositions comprising latanoprost for use in the treatment of ocular diseases
WO2019166631A1 (fr) 2018-03-02 2019-09-06 Novaliq Gmbh Compositions pharmaceutiques contenant du nébivolol
US11576893B2 (en) 2018-03-02 2023-02-14 Novaliq Gmbh Pharmaceutical compositions comprising nebivolol
US12226422B2 (en) 2018-04-27 2025-02-18 Novaliq Gmbh Ophthalmic compositions comprising tafluprost for the treatment of glaucoma

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