WO2010109417A1 - Crème médicinale antibactérienne et son procédé de production - Google Patents

Crème médicinale antibactérienne et son procédé de production Download PDF

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Publication number
WO2010109417A1
WO2010109417A1 PCT/IB2010/051280 IB2010051280W WO2010109417A1 WO 2010109417 A1 WO2010109417 A1 WO 2010109417A1 IB 2010051280 W IB2010051280 W IB 2010051280W WO 2010109417 A1 WO2010109417 A1 WO 2010109417A1
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Prior art keywords
cream
added
amount
group
combination
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PCT/IB2010/051280
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English (en)
Inventor
Sulur Subramaniam Vanangamudi
Madhavan Srinivasan
Neelakandan Narayanan Chulliel
Original Assignee
Sulur Subramaniam Vanangamudi
Madhavan Srinivasan
Neelakandan Narayanan Chulliel
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Application filed by Sulur Subramaniam Vanangamudi, Madhavan Srinivasan, Neelakandan Narayanan Chulliel filed Critical Sulur Subramaniam Vanangamudi
Priority to MX2011009934A priority Critical patent/MX2011009934A/es
Priority to CN2010800139527A priority patent/CN102365075A/zh
Priority to JP2012501462A priority patent/JP2012521410A/ja
Priority to EP10716072A priority patent/EP2410975A1/fr
Priority to BRPI1006455A priority patent/BRPI1006455A2/pt
Publication of WO2010109417A1 publication Critical patent/WO2010109417A1/fr
Priority to IL215126A priority patent/IL215126A0/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • 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
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A61K8/736—Chitin; Chitosan; Derivatives thereof
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the present invention relates to a composition for treating bacterial skin infections along with skin rejuvenation. More particularly, the present invention relates to a pharmaceutical cream comprising a biopolymer, and an antibacterial active ingredient.
  • Skin disorders can be broadly categorized as those arising from bacterial forms or fungi.
  • Antifungal or antibacterial compositions are traditionally applied as lotions, creams or ointments. Furthermore in many instances, it is difficult to ascertain whether the skin condition is due to a bacterial agent or a fungus.
  • Antibacterial or antifungal compositions are applied in turn and response monitored and treatment modified.
  • a major disadvantage of this approach is that treatment needs to be applied many times a day during the treatment period. This is greatly inconvenient and also not cost effective for a majority of human population, particularly in the under-developed countries.
  • such compositions use steroids, antibacterial agents or antifungal agents, (or a fixed dose combination of these) and focus on these pharmaceutically active ingredients.
  • the composition of such formulations is such as to enhance their physical/chemical/bio-release profile.
  • the word healing as related to compromised skin conditions are not only about prevention, control, elimination of the source cause such as bacteria or fungi but also to restore the skin to its pre-infection state.
  • the current approaches of skin treatment can be broadly categorized into two stages, a. healing b. restoration of skin to pre-ailment state.
  • the healing part comprises elimination, to the best possible extent, of the root cause of the disorder. This may be elimination of bacteria or fungi causing the infection through a suitable treatment of antibacterial or antifungal agents or reducing the inflammation through steroid treatment. While this treatment is under way, the ongoing compromised condition of the skin continues to be susceptible to secondary infections which can be of quite serious nature. In the case of scratched or wounded skin, it is important for blood clotting to occur quickly as it reduces chances of secondary infections.
  • the focus of such treatments, which are administered through creams, lotions, ointments is on the action of active pharmaceutical ingredients. Cream bases or ointment bases are merely viewed as carriers to take APIs to the sites of disorder.
  • Topical skin formulations can deliver skin healing or regeneration beyond the activity of the main APIs such that the therapeutic outcome of the main APIs
  • APIs is enhanced.
  • biologically active polymers the so-called biopolymers
  • biopolymers biologically active polymers
  • - Incorporation of a functionally bio-active excipient polymer in cream matrix while retaining the functional stability of the API in a single dose format of dermaceutical cream involves resolution of problems specific to the physical stability of cream matrix.
  • Patent applications EP2092935 and PCT/IN2008/000577 provide an insight into the typical way steroids such as Mometasone Furoate are used towards topical prescription derma products.
  • EP2092935 relates to aerosolized formulations for the treatment of asthma that contain mometasone furoate and formoterol fumarate and processes for preparing same.
  • EP2092935 claims novelty on the assertion that the aerosol suspension formulation is non-toxic, substantially free of CFCs, has improved stability, it is also easily manufacturable and is substantially free of a carrier and excipients. Further the applicant has also disclosed a process for the production of the formulation wherein dry powder of the active agents and the surfactant is mixed together and filled into a metered dose inhaler canister, followed by crimping the canister with a metering valve, and filling it with nonchlorofiuorocarbon propellant.
  • PCT/IN2008/000577 provides a treatment of inflammatory dermatoses associated with secondary bacterial infections using a combination therapy of a topical antibiotic and a topical steroid.
  • PCT/IN2008/000577 claims novelty over the existing prior art on the assertion that the applicant had found a combination which is very effective for the treatment of inflammatory dermatoses associated with secondary bacterial infections.
  • the applicant has disclosed 2 formulations of which the first formulation consists of a) 1% w/w - 5%w/w of fusidic acid; b) 0.05% w/w to 2%w/w of Mometasone furoate; and c) a pharmaceutically acceptable carrier.
  • PCT/GB2007/004373, US 6,899,897, US 6,080,744, US 6,537,970 are examples of typical usage of antifungals such as clotrimazole in prescription derma products.
  • PCT/GB2007/004373 provides medicaments and methods for the treatment of infections caused or contributed to by multi-drug resistant Staphylococcus species using effective amount of Clotrimazole, and its derivatives. It claims novelty on the assertion that the pharmaceutical composition according to the invention possesses ability of inhibiting methicillin resistant Staphylococcus species.
  • the composition described in the invention by the applicant is used for oral administration, it can be used topically at the site of an infection, or intravenously.
  • the said composition can also be used for sterilizing or cleaning solutions to decontaminate furniture, floors, equipment including for example specialized hospital equipment and/or surgical equipment
  • US 6,899,897 discloses a biological dressing comprising a sticky film of gum resin - benzoin, a pharmacologically active agent - clotrimazole is left on the skin or mucous membrane after the volatile solvent - ethanol has evaporated.
  • the composition further may include penetration enhancer. It claims novelty over the assertion that the dressing disclosed herewith is a clean and inexpensive vehicle/carrier of topically applied medications increasing the convenience and effectiveness of the treatment and decreasing the necessary time for the treatment. This is apparently associated with less waste and lower cost and improved treatment.
  • the film formed is apparently extends retention on the skin since it is resistant to water and abrasion by clothing.
  • US 6,537,970 deals with a composition comprising clindamycin and clotrimazole used for the treatment of vaginal infection. It claims novelty over the conventional therapy because of the unique combination of various mycotoxins present in the composition and synergetic effect of the same. It is also claimed that the said composition can be used for the treatment of bacterial infection, fungal infection and mixed infection. The treatment can also be carried out either orally or topically.
  • US 6,080,744 deals with a topical composition for medical, veterinary or dental use containing active antimycotic ingredients like, clotrimazole, ketoconazole, miconazole, nystatin, tolnaftate, propionic acid, sodium propionate, undecelynic acid and zinc undecelynate in a natural base such that the composition is capable of defeating a wide range of fungi and can clear topical fungal infection. It claims advantage over the existing prior art on the bases that the ingredients used in the composition is blended in natural - cream base, also it is effective over a wide range of mycological illnesses and helps in speedy recovery.
  • active antimycotic ingredients like, clotrimazole, ketoconazole, miconazole, nystatin, tolnaftate, propionic acid, sodium propionate, undecelynic acid and zinc undecelynate
  • active antimycotic ingredients like, clotrimazole, ketoconazole, miconazole, n
  • cream base matrix as a functional element of the cream rather than a mere carrier for the main APIs
  • Figure 1 Non-homogeneous nature of creams containing chitosan with non- compatible excipient such as carbomer
  • the present invention is directed to a composition for treating bacterial skin infections along with skin rejuvenation containing a) a biopolymer in the form of Chitosan b) An active pharmaceutical ingredient (APIs) used in treating bacterial skin infections. c) A cream base containing primary and secondary emulsifiers, waxy materials, co-solvents, acids, preservatives, buffering agents, anti oxidants, chelating agents, and humectants. d) Water
  • the active ingredients namely chitosan, and an antibacterial agent, are incorporated in cream base for use in treating bacterial skin infections with allergy & itching, & wounds on human skin involving contacting human skin with the above identified composition.
  • the present invention provides a uni-dose API formulation for topical skin treatment in the field of prescription medicaments.
  • the prescription medication is distinct in its use as compared with the so-called cosmeceuticals.
  • the cosmeceuticals are aimed towards beautification or betterment of a more-or-less intact skin or of a skin not suffering from a serious disorder.
  • prescription skin formulations are aimed to provide treatment for serious skin disorders resulting from infections and wounds.
  • Topical skin formulations can deliver skin healing or regeneration beyond the activity of the main APIs such that the therapeutic outcome of the main APIs are enhanced.
  • biopolymers biologically active polymers
  • incorporation of a functionally bio-active excipient polymer in cream matrix while retaining the functional stability of the API in a single dose format of dermaceutical cream involves resolution of problems specific to the physical stability of cream matrix.
  • the active compounds which may be employed in the present invention are either acid or basic actives or their salts well known in the art of treatment of bacterial infections, and a bio polymer for treating wounds and rejuvenating human skin involving contacting human skin with the above identified composition.
  • biopolymer examples include, but are not limited to chitosan and the like.
  • topical antibacterial agents include, but are not limited to, Sodium Fusidate, Calcium Mupirocin, Gentamycin, Neomycin, Silver Sulphadiazine, Ciprofloxacin, Framycetin Sulphate, Quinidochlor, Povidone-Iodine, Sisomicin, Nitrofural and the like.
  • This acid or basic active compounds or their salts require a base component to be used in the pharmaceutical composition that uses the compounds, since the compounds cannot, by themselves, be deposited directly on to human skin due to their harshness.
  • the base component usually contains primary and secondary emulsifiers, waxy materials, co-solvents, acids, preservatives, buffering agents, anti oxidants, chelating agents, humectants and the like.
  • Chitosan is a linear polysaccharide composed of randomly distributed ⁇ -(l-4)- linked D-glucosamine (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit). It is known to have a number of commercial uses in agriculture and horticulture, water treatment, chemical industry, pharmaceuticals and biomedics.
  • Chitosan generally absorbs moisture from the atmosphere / environment and the amount absorbed depends upon the initial moisture content, temperature and relative humidity of the environment. It is regarded as a non-toxic and non-irritant material. It is biocompatible with both healthy and infected skin and has been shown to be biodegradable as it is derived from shrimps, squids and crabs.
  • Chitosan due to its unique physical property accelerates wound healing and wound repair. It is positively charged and soluble in acidic to neutral solution. Chitosan is bioadhesive and readily binds to negatively charged surfaces such as mucosal membranes. Chitosan enhances the transport of polar drugs across epithelial surfaces. Chitosan's properties allow it to rapidly clot blood, and it has recently gained approval in the USA for use in bandages and other hemostatic agents.
  • Chitosan is no nailer genie, and has natural anti-bacterial properties, further supporting its use. As a micro-film forming biomaterial, Chitosan helps in reducing the width of the wound, controls the oxygen permeability at the site, absorbs wound discharge and gets degraded by tissue enzymes which are very much required for healing at a faster rate. It also reduces the itching by providing a soothing effect. It also acts like a moisturizer. It is also useful in treatment of routine minor cuts and wounds, burns, keloids, diabetic ulcers and venous ulcers. Chitosan used in the present invention comes in various molecular weights ranging from lkdal to 5000kdal.
  • Chitosan is discussed in the USP forum with regard to its functional excipient category. Since chitosan is basically a polymer, it is available in various grades depending upon the molecular weight. The various grades of chitosan include chitosan long chain, chitosan medium chain & chitosan short chain, the grades long, medium & short chain directly correspond to the molecular weight of the chitosan.
  • the long chain grade has a molecular weight in the range of 500,000- 5,000,000 Da
  • the medium chain grade has a molecular weight in the range of 1,00,000-2,000,000 Da
  • the short chain grade has a molecular weight in the range of 50,000-1,000,000 Da.
  • the molecular weight of the chitosan plays an important role in the formulation.
  • Higher molecular weight chitosan imparts a higher viscosity to the system and lower molecular weight chitosan imparts a lower viscosity to the system.
  • medium chain grade chitosan delivered an optimum level of viscosity to the formulation. Since the dosage form is a cream, appropriate levels of viscosity is required to achieve a good spreadability over the skin.
  • the inventors finalized the chitosan medium chain grade for the present invention since it imparted the required rheologic properties to the cream without compromising the therapeutic activity of both the actives and chitosan.
  • the concentration of chitosan medium chain grade was carefully arrived based on several inhouse trials and Preclinical animal studies for efficacy.
  • Topical Antibacterials are intended to target skin for bacterial infections caused by Staphylococcus aureus, Staphylococcus epidermidis, Methicillin - resistance Staphylococcus aureus (MRSA) etc.
  • Anti-bacterials act by inhibiting cell wall synthesis by combining with bacterial ribosomes and interfering with mRNA ribosome combination.
  • Topical antibacterial agents include, but are not limited to, Sodium Fusidate, Calcium Mupirocin, Gentamycin, Neomycin, Silver Sulphadiazine, Ciprofloxacin, Framycetin Sulphate, Quinidochlor, Povidone-Iodine, Sisomicin, Nitrofural and the like.
  • Creams are topical preparation used for application on the skin.
  • Creams are semisolid emulsions, which are mixtures of oil and water in which APIs (Active
  • Oil-in-water (OAV) creams which compose of small droplets of oil dispersed in a continuous water phase
  • W/O water-in-oil
  • Oil-in-water creams are user-friendly and hence cosmetically acceptable as they are less greasy and more easily washed with water.
  • An ointment is a viscous semisolid preparation containing APIs, which are used topically on a variety of body surfaces.
  • the vehicle of an ointment is known as ointment base. The choice of a base depends upon the clinical indication of the ointment, and the different types of ointment bases normally used are:
  • Hydrocarbon bases e.g. hard paraffin, soft paraffin
  • Absorption bases e.g. wool fat, bees wax
  • the acidic scale of pH is from 1 to 7, and the base scale of pH is from 7 to 14.
  • Human skins pH value is some where between 4.5 and 6. Newborn baby's skin pH is closer to neutral (pH 7), but it quickly turns acidic. Nature has designed this probably to protect young children's skin, since acidity kills bacteria. As people become older, the skin becomes more and more neutral, and won't kill as many bacteria as before. This is why the skin gets weak and starts having problems.
  • the pH value goes beyond 6 when a person actually has a skin problem or skin disease. This shows that it is necessary to choose topicals that have a pH value close to that of skin of a young adult.
  • cream formulations are available as creams. Active compounds in cream formulations are available in ionized state, whereas in case of ointments these are present in non-ionized state.
  • the cream formulations are the first choice of the formulators in design and development of topical dosage forms, as the cream formulations are cosmetically elegant, and also as the active compound is available in ionized state, and the drug can penetrate the skin layer fast which makes the formulation totally patient friendly.
  • the pH of the cream of the present invention with a functional biopolymer such as Chitosan, steroids, anti fungal agent is from about 3 to 6.
  • a functional biopolymer such as Chitosan, steroids, anti fungal agent
  • ointments that are commercially available are greasy and cosmetically non elegant.
  • the active compound in an ointment is in non-ionized form, the penetration of skin is slow.
  • the active drug penetrates the skin for the optimum bio-dermal efficacy.
  • the particle size of the active drug plays an important role here. It is necessary that the active drug is available in colloidal or molecular dispersed state for the product being highly efficacious form. Also this is to be achieved in the safe pH compatible environment of skin (4.0 to 6.0). To achieve all these, it is essential to choose proper vehicles or co-solvents for the dissolution or dispersion of the drug.
  • the product of the present invention is highly efficacious due to the pronounced antibacterial & wound healing activity of the active ingredients, which are available in ultra micro-size, colloidal form, which enhances skin penetration.
  • Topical antibacterial agents have profound efficacy in primary & secondary bacterial skin infections of varied etiology due to its antibacterial properties.
  • a drawback of the monotherapy with any topical antibacterial has been the relatively slow onset of the effect. .
  • chitosan By employing antibacterial & chitosan in a formulation, the properties of both antibacterials and chitosan are optimized.
  • chitosan is film forming, biocompatible, non-allergenic material it helps in protecting the skin by acting as a barrier. It further controls the superficial bleeding caused by scratching and also arrests the mobility of pathogens due to its cationic charge.
  • chitosan in the formulation takes care of many attributes, which are considered to be very much essential in treating skin ailments.
  • the combination of chitosan with antibacterial is unique and novel since this is not available commercially across the globe.
  • Another inventive aspect of the present invention is that the addition of a functional excipient in the cream base is not a straight forward process of mere addition.
  • the inventor has found that the compatibility of the functional excipient such as chitosan with other agents in the cream is of critical importance. This is because incompatibility would compromise the stability of the final product.
  • the inventors have found that well known excipients such as Xanthan Gum and carbopol which have been variously used as stabilising agents, cannot be used in combination with functional biopolymers such as chitosan.
  • Excipients for topical dosage forms include Polymers, Surfactants, Waxy Materials, Emulsifiers etc. Polymers are used as gelling agents, suspending agents, viscosity builders, release modifiers, diluents, etc. Surfactants are used as wetting agents, emulsifiers, solubilising agents release enhancers, etc.
  • Polymers & Surfactants may or may not possess ionic charge. They may be anionic or cationic or non-ionic in nature. If anionic excipients are included in the formulation they interact with cationic formulation excipients and produce products which are not homogenous, aesthetically not appealing and give rise to unwanted by products, possible allergens, impurities, toxic substances etc due to incompatibility.
  • the final product was also not aesthetically appealing without homogeneity.
  • the attached figure 1 clearly explains the interaction between chitosan and unsuitable anionic excipients. Based on the observations and thorough knowledge about the excipients, the inventors arrived at a robust formula without any possible interactions.
  • tablettes 1 to 5 are examples of products that do not form homogeneous creams, and produce non-homogeneous creams of the type illustrated in figure 1. Yet the proportions stated in these examples are some things that a person skilled in the art may use based currently available knowledge. Only after a thorough and extensive trials and errors would it be possible to arrive at right types and proportions of excipients.
  • antibacterials provide relief against bacterial infections.
  • the aspects such as like skin protection, bleeding at the site, mobility of pathogens from one site to another, etc are not addressed so far in a single dose therapy.
  • This present invention with its single-dose application fills this gap by incorporating chitosan and tapping the required benefits of skin protection (by way of film forming property), stopping the bleeding (by way of blood clotting property) and immobilization of pathogenic microbes (due to its cationic electrostatic property).
  • Therapeutic value addition by incorporation of a functional excipient in the form of a chitosan which is a biopolymer in the cream matrix.
  • the value addition is an integrated sub-set of the following functional attributes of the biopolymer: formulation of a micro-film on the skin surface accelerated blood clotting as compared to creams that do not contain film- forming biopolymers electrostatic immobilisation of surface microbes due to cationic charge of the biopolymer - significant enhancement of the skin epithelisation or regeneration
  • inventive efforts involved in developing the platform technology covered by incorporation of a functional biopolymer in prescription dermaceutical products are: in identification of the complementary therapeutic value that such incorporation delivers in identification of issues related to physio -chemical stability of the product resulting from the incorporation of the biopolymer in providing a single dose format where the bacterial infection has been identified.
  • the unique innovative formulation of the present invention takes care of the skin conditions by treating them along with controlling the superficial bleeding at the site. It is well understood that if the superficial bleeding is left untreated, it will lead to secondary microbial infections.
  • the present invention advantageously provides a solution to this unmet need.
  • the present invention with its single-dose therapy reduces the overall treatment time of a serious skin disorder significantly.
  • a novel dermaceutical cream for topical treatment of bacterial skin infections, and for related wound healing wherein said cream comprises an antibacterial agent, and a biopolymer provided in a cream base, said cream base comprising at least one of each of a preservative, a primary and a secondary emulsifier, a waxy material, a co-solvent, an acid, and water, preferably purified water.
  • said antibacterial agent is added in an amount between about 0.5% w/w and about 15% w/w, more preferably between 0.5 and 5.0% w/w; and, said biopolymer is in the form of chitosan, added in an amount between about 0.01% and about 1% by weight, preferably from about 0.01% w/w to about 0.5% w/w and most preferably about 0.25% w/w, said chitosan being US pharmacopeia conformant with regard to its functional excipient category and selected from any grades such as long chain, medium chain & short chain, and has a molecular weight in the range between 5OkDa to 5000 kDa,
  • said primary and secondary emulsifiers are selected from a group comprising Cetostearyl alcohol, Cetomacrogol-1000, Cetyl alcohol, Stearyl alcohol, Polysorbate-80, Span-80 and the like and added in an amount from about 1% (w/w) to 20% (w/w); said waxy materials is selected from a group comprising white soft paraffin, liquid paraffin, hard paraffin and the like, or any combination thereof, from about 5% (w/w) to 50% (w/w); said co-solvent is selected from a group comprising Propylene Glycol, Hexylene Glycol, PolyEthylene Glycol-400 and the like, or any combination thereof, and added in an amount from about 5% (w/w) to 50% (w/w); said acid is selected from a group comprising HCl, H 2 SCU, HNO 3 , Lactic acid and the like, or any combination thereof, and added in an amount from about 0.005% (w/w) to 0.5% (w/w/
  • Embodiment no. 3 is a diagrammatic representation of Embodiment no. 3:
  • a buffering agent which is selected from a group comprising Di Sodium Hydrogen Ortho Phosphate, Sodium Hydrogen Ortho Phosphate, Calcium lactate and the like, or any combination thereof, and added in an amount from about 0.05% (w/w) to 1.00% (w/w).
  • Embodiment no. 4 A novel cream as disclosed in the preferred embodiment no. 1 and the embodiments no. 2 and 3, further comprising an antioxidant which is selected from a group comprising Butylated Hydroxy Anisole, Butylated Hydroxy Toluene and the like, or any combination thereof, and added in an amount from about 0.05% (w/w) to 5% (w/w).
  • an antioxidant which is selected from a group comprising Butylated Hydroxy Anisole, Butylated Hydroxy Toluene and the like, or any combination thereof, and added in an amount from about 0.05% (w/w) to 5% (w/w).
  • Embodiment no. 5 A novel cream as disclosed in the preferred embodiment no. 1 and the embodiments no.2 to 4, further comprising a chelating agent which is selected from a group comprising Disodium EDTA and the like, or any combination thereof, and added in an amount from about 0.05% (w/w) to 1% (w/w).
  • a chelating agent which is selected from a group comprising Disodium EDTA and the like, or any combination thereof, and added in an amount from about 0.05% (w/w) to 1% (w/w).
  • Embodiment no. 6 A novel cream as disclosed in the preferred embodiment no. 1 and the embodiments no. 2 to 4, further comprising a humectant which is selected from a group comprising Glycerin, Sorbitol, and the like, or any combination thereof, and added in an amount from about 5% (w/w) to 50% (w/w).
  • a humectant which is selected from a group comprising Glycerin, Sorbitol, and the like, or any combination thereof, and added in an amount from about 5% (w/w) to 50% (w/w).
  • Embodiment no. 7 A novel cream as disclosed in the preferred embodiment no. 1 and the embodiments no. 2 to 4, further comprising a stabilizer which is selected from a group comprising Guar gum and the like, or any combination thereof, and added in an amount from about 0.1 % (w/w) to 5% (w/w).
  • a stabilizer which is selected from a group comprising Guar gum and the like, or any combination thereof, and added in an amount from about 0.1 % (w/w) to 5% (w/w).
  • Embodiment no. 8 A process of making a cream is disclosed, said process comprising the steps of providing an antibacterial agent, and a biopolymer in a cream base comprising at least one of each of a preservative, a primary and a secondary emulsifier, a waxy material, a co-solvent, an acid, and water, preferably purified water, and mixing all the ingredients together to form a homogeneous cream.
  • Embodiment no. 9 A process of making a cream as disclosed in the embodiment no. 7, wherein the ingredients further comprise any of a group comprising a buffering agent, an antioxidant, a chelating agent, a humectant, a stabilizer or any combination thereof.
  • Embodiment no. 10 A novel cream as disclosed in any of the foregoing embodiments, wherein chitosan has a molecular weight range of lkdal to 5000kdal.
  • Example-I Table 6:_Sodium Fusidate + Chitosan Cream
  • Example-III Table 8: Framycetin Sulphate + Chitosan Cream
  • Example-IV Table 9: Silver Sulphadiazine + Chitosan Cream
  • APIs-stability experiments were carried out (see tables 10- 21) using the product of the present invention. Tests were carried out to observe (or measure as appropriate) the physical appearance of the product, the pH value and assay of the APIs over a period of time.
  • Each gram of product of the present invention used for the tests contained appropriate amount of antibacterials.
  • Each gm contains: Sodium Fusidate BP Equivalent to Fusidic
  • Measured parameter pH; Limits of measured parameter: 3-6 Method of measurement: Di ital H Meter
  • PRODUCT CALCIUM MUPIROCIN CREAM
  • composition Each gm contains!) Calcium Mupirocin USP equivalent to
  • PRODUCT FRAMYCETIN SULPHATE CREAM
  • Each gm contains: i) Framycetin Sulphate IP 1.0 % w/w
  • Each gm contains: i) Silver Sulphadiazine USP 1.0 % w/w
  • Measured parameter pH; Limits of measured parameter: 3-6 Method of measurement: Digital pH Meter
  • the cream is applied after thorough cleansing and drying the affected area. Sufficient cream should be applied to cover the affected skin and surrounding area. The cream should be applied two - four times a day depending upon the skin conditions for the full treatment period, even though symptoms may have improved.
  • Excision wound healing activity of the cream of the present invention was determined through animal testing. An excision wound 2.5 cm in diameter was inflicted by cutting away full thickness of the skin. The amount of contraction of the wound observed over a period indicated that the cream of present invention provides significantly improved wound contraction than that achieved through application of a conventional cream.
  • one benefit of the cream of the present invention is that it facilitates faster epithelisation of the skin than through the use of conventional creams.
  • Blood clotting time was observed in both group of animals, untreated control group and the test group of animals treated with the product of the present invention. Statistically significant decrease in the blood clotting time in treated group animals was observed when compared with that of the control group animals. The mean percent reduction of 20-70% was observed for the blood clotting time using the product of the present invention.
  • topically applied cream of the present invention is due to the pronounced antibacterial activity of the actives against the organisms responsible for skin infections, the unique ability of actives to penetrate intact skin and wound healing & soothing properties of chitosan.
  • the cream of the present invention incorporates a skin-friendly biopolymer in the form of chitosan provides enhanced therapeutic outcomes. This is evident from the reduced blood clotting time, increased epithelial effect, and faster relief from infection.
  • the cream of the present invention incorporates a biopolymer without compromising the stability of the cream matrix and without adversely affecting the functioning of known active pharmaceutical ingredients. This has been achieved through a careful selection of functional excipients to bypass undesirable aspects of physio- chemical compatibility/stability and bio-release.
  • the cream of the present invention provides an integrated uni-dose or a single-dose therapy hitherto unavailable in prescription dermaceutical formulations.
  • the novel cream of the present invention is adequately stable/efficacious at ambient conditions and does not need special temperature control during transportation/storage - hence will go a long way in achieving these social objectives.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
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  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Inorganic Chemistry (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Cosmetics (AREA)

Abstract

L'invention concerne une composition pour traiter des infections cutanées bactériennes et induire une régénération cutanée. Cette invention se rapporte de manière plus spécifique à une crème pharmaceutique comprenant un biopolymère, et un principe actif antibactérien. La composition selon l'invention qui sert à traiter des infections cutanées bactériennes et à induire une régénération cutanée, contient : a) un biopolymère se présentant sous la forme a) de chitosane, b) un principe actif pharmaceutique destiné à traiter des infections cutanées bactériennes, c) une base de crème renfermant des émulsifiants primaires et secondaires, des substances cireuses, des cosolvants, des acides, des conservateurs, des tampons, des anti-oxydants, des chélateurs, des humectants, et d) de l'eau. Les principes actifs, à savoir le chitosane et un agent antibactérien, sont incorporés dans la base de crème et servent à traiter les infections cutanées bactériennes.
PCT/IB2010/051280 2009-03-25 2010-03-24 Crème médicinale antibactérienne et son procédé de production WO2010109417A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
MX2011009934A MX2011009934A (es) 2009-03-25 2010-03-24 Crema antibacteriana medicinal y proceso para hacerla.
CN2010800139527A CN102365075A (zh) 2009-03-25 2010-03-24 医用抗菌乳膏和其制备方法
JP2012501462A JP2012521410A (ja) 2009-03-25 2010-03-24 薬用抗細菌クリームおよびその作製方法
EP10716072A EP2410975A1 (fr) 2009-03-25 2010-03-24 Crème médicinale antibactérienne et son procédé de production
BRPI1006455A BRPI1006455A2 (pt) 2009-03-25 2010-03-24 creme sntibacteriano medicinal e processo para a fabricação do mesmo
IL215126A IL215126A0 (en) 2009-03-25 2011-09-13 A medicinal antibacterial cream and a process to make it

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN701MU2009 2009-03-25
IN701/MUM/2009 2009-03-25

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WO2010109417A1 true WO2010109417A1 (fr) 2010-09-30

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JP (1) JP2012521410A (fr)
CN (1) CN102365075A (fr)
BR (1) BRPI1006455A2 (fr)
IL (1) IL215126A0 (fr)
MX (1) MX2011009934A (fr)
WO (1) WO2010109417A1 (fr)

Cited By (7)

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WO2010119369A2 (fr) * 2009-04-13 2010-10-21 Sulur Subramaniam Vanangamudi Crème médicale à base de sulfadiazine d'argent et de chitosane et son procédé de préparation
WO2012049543A1 (fr) * 2010-10-15 2012-04-19 Sulur Subramaniam Vanangamudi Crème médicinale à base d'acide fusidique réalisée au moyen de fusidate de sodium et par incorporation d'un biopolymère et d'un corticostéroïde, et procédé permettant de fabriquer une telle crème
WO2012049545A1 (fr) * 2010-10-12 2012-04-19 Sulur Subramaniam Vanangamudi Crème médicinale à base d'acide fusidique réalisée au moyen de fusidate de sodium et par incorporation d'un biopolymère, procédé permettant de fabriquer une telle crème
WO2012049541A1 (fr) * 2010-10-15 2012-04-19 Sulur Subramaniam Vanangamudi Crème médicinale à base d'acide fusidique réalisée au moyen de fusidate de sodium et par incorporation d'un biopolymère et d'un corticostéroïde, et procédé permettant de fabriquer une telle crème
WO2021079254A1 (fr) * 2019-10-24 2021-04-29 Sulur Vishagan Vanangamudi Composition pharmaceutique, contenant un antibiotique topique, contre les infections bactériennes et pour la cicatrisation des plaies
GB2597445A (en) * 2020-07-21 2022-02-02 Hydrodyne Systems Ltd An antimicrobial cosmetic preparation
RU2812927C1 (ru) * 2019-10-24 2024-02-05 Вишаган Ванангамуди СУЛУР Антибиотик для местного применения, содержащий фармацевтическую композицию для лечения бактериальных инфекций и заживления ран

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CN105640795B (zh) * 2014-11-28 2019-06-07 上海家化联合股份有限公司 一种含多元醇和乳酸的温和性组合物的制备与应用

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010119369A2 (fr) * 2009-04-13 2010-10-21 Sulur Subramaniam Vanangamudi Crème médicale à base de sulfadiazine d'argent et de chitosane et son procédé de préparation
WO2010119369A3 (fr) * 2009-04-13 2011-11-10 Sulur Subramaniam Vanangamudi Crème médicale à base de sulfadiazine d'argent et de chitosane et son procédé de préparation
US9044488B2 (en) 2009-04-13 2015-06-02 Vanangamudi Sulur Subramaniam Medicinal cream made using silver sulphadiazine and chitosan and a process to make it
WO2012049545A1 (fr) * 2010-10-12 2012-04-19 Sulur Subramaniam Vanangamudi Crème médicinale à base d'acide fusidique réalisée au moyen de fusidate de sodium et par incorporation d'un biopolymère, procédé permettant de fabriquer une telle crème
WO2012049543A1 (fr) * 2010-10-15 2012-04-19 Sulur Subramaniam Vanangamudi Crème médicinale à base d'acide fusidique réalisée au moyen de fusidate de sodium et par incorporation d'un biopolymère et d'un corticostéroïde, et procédé permettant de fabriquer une telle crème
WO2012049541A1 (fr) * 2010-10-15 2012-04-19 Sulur Subramaniam Vanangamudi Crème médicinale à base d'acide fusidique réalisée au moyen de fusidate de sodium et par incorporation d'un biopolymère et d'un corticostéroïde, et procédé permettant de fabriquer une telle crème
WO2021079254A1 (fr) * 2019-10-24 2021-04-29 Sulur Vishagan Vanangamudi Composition pharmaceutique, contenant un antibiotique topique, contre les infections bactériennes et pour la cicatrisation des plaies
RU2812927C1 (ru) * 2019-10-24 2024-02-05 Вишаган Ванангамуди СУЛУР Антибиотик для местного применения, содержащий фармацевтическую композицию для лечения бактериальных инфекций и заживления ран
GB2597445A (en) * 2020-07-21 2022-02-02 Hydrodyne Systems Ltd An antimicrobial cosmetic preparation
GB2597445B (en) * 2020-07-21 2022-11-09 Hydrodyne Systems Ltd An Antimicrobial Cosmetic Preparation

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EP2410975A1 (fr) 2012-02-01
BRPI1006455A2 (pt) 2018-02-27
MX2011009934A (es) 2011-10-06
CN102365075A (zh) 2012-02-29
JP2012521410A (ja) 2012-09-13

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