WO2002080962A1 - Papaine containing pharmaceutical formulation resp. its use - Google Patents
Papaine containing pharmaceutical formulation resp. its use Download PDFInfo
- Publication number
- WO2002080962A1 WO2002080962A1 PCT/BR2001/000044 BR0100044W WO02080962A1 WO 2002080962 A1 WO2002080962 A1 WO 2002080962A1 BR 0100044 W BR0100044 W BR 0100044W WO 02080962 A1 WO02080962 A1 WO 02080962A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- epitheliums
- papaine
- permeability
- coating
- pharmaceutical composition
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 18
- 238000009472 formulation Methods 0.000 claims abstract description 10
- 208000004362 Penile Induration Diseases 0.000 claims abstract description 8
- 208000020758 Peyronie disease Diseases 0.000 claims abstract description 8
- 108010003272 Hyaluronate lyase Proteins 0.000 claims abstract description 7
- 102000001974 Hyaluronidases Human genes 0.000 claims abstract description 7
- 229960002773 hyaluronidase Drugs 0.000 claims abstract description 7
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims abstract description 5
- 230000007170 pathology Effects 0.000 claims abstract description 4
- 229930003427 Vitamin E Natural products 0.000 claims abstract description 3
- 230000003176 fibrotic effect Effects 0.000 claims abstract description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229940046009 vitamin E Drugs 0.000 claims abstract description 3
- 235000019165 vitamin E Nutrition 0.000 claims abstract description 3
- 239000011709 vitamin E Substances 0.000 claims abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000006071 cream Substances 0.000 claims description 6
- 239000000499 gel Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 239000000443 aerosol Substances 0.000 claims description 2
- 239000008346 aqueous phase Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims 1
- 238000000265 homogenisation Methods 0.000 claims 1
- 238000010348 incorporation Methods 0.000 claims 1
- 210000000981 epithelium Anatomy 0.000 description 82
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- 238000000576 coating method Methods 0.000 description 38
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- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
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- 208000035484 Cellulite Diseases 0.000 description 3
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- 208000032544 Cicatrix Diseases 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
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- 102000004169 proteins and genes Human genes 0.000 description 3
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 208000001708 Dupuytren contracture Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 208000002260 Keloid Diseases 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
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- 239000011253 protective coating Substances 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
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- 206010002329 Aneurysm Diseases 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 206010070653 Penile curvature Diseases 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
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- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
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- 229910052742 iron Inorganic materials 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- 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
- A61K31/355—Tocopherols, e.g. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01035—Hyaluronoglucosaminidase (3.2.1.35), i.e. hyaluronidase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/22—Cysteine endopeptidases (3.4.22)
- C12Y304/22002—Papain (3.4.22.2)
Definitions
- the present invention refers to a new pharmaceutical composition, to be used in any pharmaceutical form, most notably gel, cream and cream gel, liquid, spray, aerosol, lyophilized used for treating the Peyronie disease and based on bro eline, as well as its process of obtainment.
- the above mentioned pharmaceutical composition is of topical application, non-toxic, featuring debridant and anti- inflammatory action with a high penetration rate through the skin.
- the skin permeability varies according to the region of the body, being the skin folds and the face those that present the highest absorption rate. A product applied over the skin will present a longer period of contact and percutanial absorption.
- the epithelium cells are predominantly classified into two categories, which correspond to two epithelium classes: coating epithelium cells and secreting epithelium cells.
- the cells of these two classes mix with each other to constitute, respectively, the coating epithelium and the secreting epithelium, each one of them performing specific functions that are inherent to them.
- Such division is also fundamented in the distribution of these two classes of epithelium in the organism, which although wide is distinctive for both.
- the epithelium cells associate side-by-side, so as to originate "membranes” or layers superimposed over the base membrane, which function is to coat surfaces.
- the secreting cells unite to form organized functional units, better suited for performing their specialized function, related to the secretion products synthesis; thus are constituted the secreting units.
- the coating epitheliums are defined as living membranes, usually featuring a discontinuity, that isolate the organism from the environment, separating the internal media from the external one. Furthermore, these epitheliums isolate from each other the various internal media compartments, among which are the intravascular compartment, the serum compartment and several others.
- the coating epitheliums include those that are performed by specialized variants that are specifically adapted to perform one or more functions. Others are incorporated as general functions presented without distinction by every coating epithelium cell.
- the coating epithelium cell in the same way as most of the living cells, passively absorbs water and electrolytes and eliminates them actively; this function is well developed in the epithelium cells. On that account it is very important to observe that generally it is understood as absorption the penetration of solutions through the cells plasmatic membrane.
- the coating epithelium cells limit in a controlled and selective way the permeability of the respective epitheliums, with the purpose of protecting the organism and still participate of the control of its homeostasis.
- the epitheliums are organized and arrange their cells in a special form, in order to build up coatings which cells abut the base membrane and are united with each other by means of intracellular junctions; in turn the cells are coated by the plasmatic membrane, which features special characteristics, and by the glicochalice, both able to express well defined functional properties.
- the functional characteristics expressed by the plasmatic membrane portion that coats the cells apical surface are different from those expressed by the portion situated in its basal or basolateral face; such differences, which occur mainly on the functional aspect, contribute for the remarkable degree of polarization expressed by the coating epithelium cells.
- the prime function performed by the coating epitheliums correspond essentially to the protection rendered to the surface that they coat, characterizing their protective coating function. Such function features a special characteristic, being a coating that, besides offering mechanical, physical and chemical protection to the coated surface, is not inert.
- the coating epitheliums are pervious, which allows for the controlled and selective passage of several products through its wall.
- the coating epitheliums permeability constitutes a fundamental property, with significant functional expression, for it is essential for the performance of several functions featured by the epitheliums, even more so because it is selective and its permeability degree presents a wide variation. It is fairly well demonstrated that the permeability degree influences strongly the function performed by the coating epitheliums:
- the epitheliums allow intense metabolic exchanges through their walls, with poor control and selectivity of its permeability.
- the epithelium acts on the filtration and transfer of metabolytes, these functions requiring little qualitative control; the exercise of these functions is subordinated to the epithelium intrinsic structure, which is adapted to act, mainly passively, being low the level of selective permeability.
- these coating epitheliums present selective permeability, which allows them to interfere and qualitatively control their functional activity, as well as making them more able to actuate over the homeostasis control.
- the absence of epithelium permeability is correlated to the complex isolation of the coated surface and, on the other hand, to the better controlling of this epithelium function, because its cells, although very poorly pervious, present selective permeability.
- the coated surface has its boundaries limited by a "membrane" impervious or very poorly pervious and very effective, that performs an important protective function, for it is able to discriminate exactly what can cross the epithelium.
- the coating epitheliums permeability is such an expressive functional property that it has been used as an important classification criterion to rank them in three classes :
- the epitheliums Because of their selective permeability, even in the inferior animals the epitheliums have assumed the function of coating the organism, constituting its external coating, with limiting and protective properties, not only morphological but also functional. Their cells, in principle very similar, behaved as a semi-pervious "membrane" poorly effective that acted passively, but which function allowed the separation, tough precarious and more morphological than functional, between the internal and the external media. It seem to be that the majority of the coating epitheliums acts as a barrier that prevents the free passive diffusion, because their permeability, which is selective, is conditioned to several factors among which stands out the electric potential present in their cells plasmatic membrane.
- the continuity of the epithelium coating is established as much through the intimate abutment of adjacent cells as through the presence of intercellular union devices.
- the epithelium cells are enveloped by the glicochalice, that also takes part of the coating function performed by the epithelium, in addition to aid the union between adjacent cells, because the intracellular adhesive is formed also by the glicochalice.
- glicochalice that also takes part of the coating function performed by the epithelium, in addition to aid the union between adjacent cells, because the intracellular adhesive is formed also by the glicochalice.
- the first four derive mostly from the epithelium cells selective permeability, over which are additionally superimposed the additional affects corresponding to their properties of absorption, excretion and secretion.
- the selective permeability is responsible by the efficiency regarding the ability to coat, protect and isolate the surfaces, as well as to effect the control of the homeostasis; the passive absorption and the metabolytes transfer capacity are executed normally by the majority of the cells of these epitheliums, which demand only minor adaptations to become able to effectively perform such functions.
- the functions of absorption, excretion and secretion depend of properties that develop successively and would become paramount, mostly in some specialized types of coating epithelium, which adapted following a new and specific direction.
- the sensorial perception and the germinative function are more specific functions that are only manifest by certain epitheliums even more specialized.
- the coating epitheliums have been classified according to the same number of cellular extracts they bear in: simple (a single extract) and stratified (two or more extracts). Both the simple epitheliums and the stratified ones, conforming to their cells format, are in turn subdivided into pavimentous, cubic or prismatic.
- the simple epitheliums are usually adapted to manifest wholly their most expressive fundamental property that consists in their permeability, which degree and selectivity vary.
- the simple coating epitheliums constituted by a single layer of pavimentous or cubic-prismatic cells, present major differences regarding their functional properties, correlated not only to their cell's morphology, but also to the intracellular space's properties.
- the simple pavimentous epitheliums are usually very pervious; the cubic-prismatic ones are less pervious.
- the coating epitheliums permeability, in addition to being selective, is controlled by their cell's functional activity, although the control looses efficiency in the same order as the intracellular space's permeability increases.
- the cubic-prismatic epitheliums being less pervious than the pavimentous, are more effective to control their permeability.
- the simple coating epitheliums are divided into two classes: pavimentous and cubic-prismatic . Each class is subdivided according to its functional properties in open or pervious epitheliums, in semi-occlusive or poorly-pervious and occlusive or impervious.
- the cubic epitheliums and the prismatic epitheliums are usually considered distinct, being defined and identified according to the format of the epithelium cells that make them up.
- some functional studies have showed that the correlation between form and function presents several exceptions. For this reason a functional classification is adopted considering predominantly it's permeability.
- these epitheliums are denominated cubic-prismatic comprising the semi-occlusive and occlusive epitheliums.
- the stratified epitheliums can be subdivided into: pavimentous and cubic- prismatic.
- the stratified epitheliums are adapted to perform primarily the mechanical protection function, because they are impervious or poorly pervious.
- the epitheliums comprise, in addition to the cells, the intercellular space and the base membrane, which interfere in their permeability degree; their permeability derives not only from their cell's peculiar properties, responsible for the transcellular permeability way, but also from the presence of another permeability way of their walls, constituting the intercellular or paracellular way.
- the transcellular way comprises two different ways that consist of the transmembranous way and the transcannular or trancitose way. It has been demonstrated, experimentally, that the coating epitheliums can be transposed by water and by substances of various natures, both through their epithelium cells
- the epithelium cell can effect the permeability control of the epithelium through its biological activity, making this process selective.
- the epithelium cell although not behaving in a totally passive form, does not interfere directly in the transport selectivity.
- the sole form of cell active participation comprises the determination, exceptionally, the enlargement of the corresponding intercellular space.
- the epithelium cell By means of the action of the microfilaments that constitute its cito-skeleton, the epithelium cell, specially those of certain types of simple coating epitheliums pavimentous of the open type, can change its format and retract segments of its cytoplasm; thus being able to influence the size of the intercellular space and regulate it. It has been established that the transcellular permeability of the simple coating epitheliums is perfectly distinct from the intercellular permeability, because both are subordinated to very different mechanisms. The epithelium cell permeability, which is selective, is influenced by its biological activity; on the contrary, the intercellular permeability is totally passive, and thus is not selective.
- the patients of group II yielded the following results: 60% complete remission of the lesion, 20% partial remission and 20% did not feature any improvement.
- protheolytic activity refers to the involvement of proteases (chemiotripcine and catepcine) and on the collagenase which, currently, not only makes easier the destruction of foreign bodies, but also hydrolyzes the collagen, whose resulting peptides act as a chemotherapic substance stimulating the proliferation of fibroblasts .
- proteases chemiotripcine and catepcine
- the observation of wounds treated with papaine shows that the granulation tissue is better developed with a higher number of fibroblasts and collagenous fibers, given the fact that the papaine may inclusively aid the digestion of the denatured collagen.
- the papaine solution acted just like the other proteases, or in other words, digesting tissue residues of protein nature that resulted in peptides, which are chemotactic for the fibroblasts, stimulating the early fiberplasy in the group treated with 2% papaine solution promoting a more effective tissue healing in the superficial and deep regions of wounds with fibrosis and keloids, thus being an effective alternative, non-invasive for the treatment of the Peyronie disease.
- composition materials which, in a period ranging from 8 to 12 months was applied directly on the penis, consisting of: application of the present formulation, during 30 minutes without removal of the same in order to ensure the penetration; this application was conducted in the dorsal and lateral areas up to the pendulum area, with no need of application on the gland.
- the applicant created the present cream composition applied to the treatment of the Peyronie disease which activated the action of the protheolytic enzymes with debridant and anti-inflammatory activities in the healing of fibrous lesions.
- microcirculatory unit qualified as rotative plate of the cellular life, is a center of equilibrium of tissues, therefore the various vascular systems must adapt to the circulatory variations.
- the venous stasis causes an increase in the intracapillar pressure. It generates an increase in the capillar permeability, which translates into the outflow of liquids and proteins of high molecular weight towards the conjunctive tissue.
- the excess of permeability and the interstitial flooding originate a lymphatic overload, which causes an edema.
- the liberation of aggressive substances, such as histamine, serotonine and prostaglandines unchain a series of tissue reactions. If the protein excesses are not depolymerized by the macrophages, there occurs a fibroblasts stimulation and the installation of fibrosis, which in turn keeps and makes worse the a venocapillar-lymphatic stasis closing down the pathologic circle.
- Interstitial Edema a consequence of the venous stasis and of excessive capillar permeability, featuring capillar distension, increase in the passage of liquids and the appearance of edemas in the conjunctive tissue core with lymphatic overload.
- the adipocytes get hypertrophied and bound together in a block.
- Micro-nodules Formation of Micro-nodules, Later Macro- nodules : the adipose masses group up in closed micro-nodules in the conjunctive fiber and end up forming macro-nodules that can be identified through palpation.
- Capillary Changes are the same usually observed over the evolution of the varicous disease; ectasies, aneurysm, thickening of the basal layer.
- the animals selected were adult rats ⁇ Rattus Norvegicus Albinus) .
- the treatment conduct is to spread the gel twice a day over the lesion spot.
- the estimated improvement with absence of pain amounts to 40% from 30 days onwards. After this period the fibrous hardened part (plaque) starts to soften.
- the object of the present invention is a new « PHARMACEUTICAL COMPOSITION", wherein said composition comprises more than 0.1% of papaine; measured for 100 g of cream.
- the present invention may comprise the following formulation: PAPAINE more than 0.1% VITAMIN-E from 10 to 2000mg
- HYALURONIDASE 50 to 900 utr/mg More advantageously the present invention may comprise the following formulation:
- VITAMIN-E from 10 to 2000mg
- HYALURONIDASE 50 to 900 utr/mg The process of manufacturing presents itself in the following manner: the oil and aqueous phases are heated to a temperature between 40 and 80 e C, after which the oil is incorporated in the water shaking until it reaches the room temperature; after that papaine is added, and alternatively hyaluronidase and/or vitamin E, mixing the solution.
- said cream composition of the present invention is soluble in water and glycerol, but practically insoluble in alcohol, ether and clorophormium, is inactive upon reacting with oxidizing agents such as iron, oxygen, Iodine derivatives, hydrogen peroxide and silver nitrate .
- the pharmaceutical composition of the present invention is used to treat several different pathologies, specially the Peyronie disease, the collagenoses and fibrotic pathologies .
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- Gastroenterology & Hepatology (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
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- Physical Education & Sports Medicine (AREA)
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Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/473,790 US20040146494A1 (en) | 2001-04-06 | 2001-04-06 | Papaine containing pharmaceutical formulation resp its use |
PCT/BR2001/000044 WO2002080962A1 (en) | 2001-04-06 | 2001-04-06 | Papaine containing pharmaceutical formulation resp. its use |
EP01275181A EP1539227A2 (en) | 2001-04-06 | 2001-04-06 | Papaine containing pharmaceutical formulation resp. its use |
MXPA03009100A MXPA03009100A (en) | 2001-04-06 | 2001-04-06 | Papaine containing pharmaceutical formulation resp. its use. |
CA002443018A CA2443018A1 (en) | 2001-04-06 | 2001-04-06 | Papaine containing pharmaceutical formulation resp. its use |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/BR2001/000044 WO2002080962A1 (en) | 2001-04-06 | 2001-04-06 | Papaine containing pharmaceutical formulation resp. its use |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2002080962A1 true WO2002080962A1 (en) | 2002-10-17 |
WO2002080962A8 WO2002080962A8 (en) | 2004-04-15 |
Family
ID=3946488
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/BR2001/000044 WO2002080962A1 (en) | 2001-04-06 | 2001-04-06 | Papaine containing pharmaceutical formulation resp. its use |
Country Status (5)
Country | Link |
---|---|
US (1) | US20040146494A1 (en) |
EP (1) | EP1539227A2 (en) |
CA (1) | CA2443018A1 (en) |
MX (1) | MXPA03009100A (en) |
WO (1) | WO2002080962A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10321725A1 (en) * | 2003-05-14 | 2004-12-02 | Mucos Pharma Gmbh & Co | Enzyme-containing compositions, dietetic foods and pharmaceuticals made therefrom and their use for medical purposes |
WO2009137897A1 (en) * | 2008-05-13 | 2009-11-19 | Santana Cristiano Alberto Ribe | Nanoparticles containing proteolytic enzymes for the treatment of peyronie's disease |
WO2009111083A3 (en) * | 2008-03-06 | 2010-03-25 | Halozyme, Inc. | In vivo temporal control of activ at able matrix- degrading enzymes |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8465413B2 (en) | 2010-11-25 | 2013-06-18 | Coloplast A/S | Method of treating Peyronie's disease |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB785112A (en) * | 1953-02-26 | 1957-10-23 | Donald Burton | Improvements in the treatment of hides, skins and tanning liquors therefor |
US4477434A (en) * | 1982-05-29 | 1984-10-16 | Reiko Kosaka | Medicinal compositions, foods and beverages having therapeutic effects on diseases of circulatory system and digestive system |
WO1994009816A1 (en) * | 1992-10-23 | 1994-05-11 | Teng Hian Khoe | Use of an enteric coated papain-containing food supplement for controlling auto immune diseases |
BR9801985A (en) | 1998-04-30 | 2000-02-08 | Cristiano Alberto Ribeiro Sant | Creamy composition applied in the therapy of peyronie's disease. |
WO2001054647A2 (en) * | 2000-01-28 | 2001-08-02 | Topic Empreendimentos E Participações S/C Ltda. | Pharmaceutical composition comprising carriers for products based on vitamin-e, papain and hyaluronidase |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2973300A (en) * | 1956-05-07 | 1961-02-28 | American Home Prod | Process for making antibiotic-enzyme topical film-forming compositions |
US3887703A (en) * | 1967-03-24 | 1975-06-03 | Oreal | Mucopolysaccharides, their preparation and use in cosmetic and pharmaceutical compositions |
JP3249844B2 (en) * | 1992-01-31 | 2002-01-21 | 太陽化学株式会社 | Skin cosmetics |
-
2001
- 2001-04-06 CA CA002443018A patent/CA2443018A1/en not_active Abandoned
- 2001-04-06 WO PCT/BR2001/000044 patent/WO2002080962A1/en active Application Filing
- 2001-04-06 EP EP01275181A patent/EP1539227A2/en not_active Withdrawn
- 2001-04-06 US US10/473,790 patent/US20040146494A1/en not_active Abandoned
- 2001-04-06 MX MXPA03009100A patent/MXPA03009100A/en active IP Right Grant
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB785112A (en) * | 1953-02-26 | 1957-10-23 | Donald Burton | Improvements in the treatment of hides, skins and tanning liquors therefor |
US4477434A (en) * | 1982-05-29 | 1984-10-16 | Reiko Kosaka | Medicinal compositions, foods and beverages having therapeutic effects on diseases of circulatory system and digestive system |
WO1994009816A1 (en) * | 1992-10-23 | 1994-05-11 | Teng Hian Khoe | Use of an enteric coated papain-containing food supplement for controlling auto immune diseases |
BR9801985A (en) | 1998-04-30 | 2000-02-08 | Cristiano Alberto Ribeiro Sant | Creamy composition applied in the therapy of peyronie's disease. |
WO2001054647A2 (en) * | 2000-01-28 | 2001-08-02 | Topic Empreendimentos E Participações S/C Ltda. | Pharmaceutical composition comprising carriers for products based on vitamin-e, papain and hyaluronidase |
Non-Patent Citations (1)
Title |
---|
WALTER A. HADLER; SINELI R. SILVEIRA: "Histologia dos epitelios", 1993 |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10321725A1 (en) * | 2003-05-14 | 2004-12-02 | Mucos Pharma Gmbh & Co | Enzyme-containing compositions, dietetic foods and pharmaceuticals made therefrom and their use for medical purposes |
WO2009111083A3 (en) * | 2008-03-06 | 2010-03-25 | Halozyme, Inc. | In vivo temporal control of activ at able matrix- degrading enzymes |
TWI395593B (en) * | 2008-03-06 | 2013-05-11 | Halozyme Inc | In vivo temporal control of activatable matrix-degrading enzymes |
US9775889B2 (en) | 2008-03-06 | 2017-10-03 | Halozyme, Inc. | Methods of treatment of cellulite |
US9833498B2 (en) | 2008-03-06 | 2017-12-05 | Halozyme, Inc. | Methods of treatment of collagen-mediated diseases and conditions |
WO2009137897A1 (en) * | 2008-05-13 | 2009-11-19 | Santana Cristiano Alberto Ribe | Nanoparticles containing proteolytic enzymes for the treatment of peyronie's disease |
Also Published As
Publication number | Publication date |
---|---|
EP1539227A2 (en) | 2005-06-15 |
WO2002080962A8 (en) | 2004-04-15 |
CA2443018A1 (en) | 2002-10-17 |
MXPA03009100A (en) | 2004-02-17 |
US20040146494A1 (en) | 2004-07-29 |
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