Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q7/00—Preparations for affecting hair growth
• • 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
  • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
  • A61K38/22—Hormones
  • A61K38/2221—Relaxins
• • 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
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
  • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
  • A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
• • 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
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/63—Steroids; Derivatives thereof
• • 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
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• each hair follicle goes through repeated cyclical periods of growth including an active growth stage (anagen), which can persist for approximately 2 to 6 years; a transition phase (catagen), which lasts for only a week or two; and a resting period (telogen), which lasts 3 to 4 months.
• anagen active growth stage
• catagen transition phase
• telogen resting period
• the hair is shed at the end of the telogen phase, and a new hair is grown as the cycle repeats
• the human scalp which contains approximately 100,000 hair follicles, normally about 86% are in anagen, 1 % are in catagen and 13% are in telogen. Therefore, in a normal human adult, approximately 100 hairs are shed from the scalp per day.
• Excessive hair loss, or alopecia may be classified as being one of two types, non-scarring alopecia and scarring alopecia, and can be caused by a wide variety of factors.
• non-scarring alopecia has been attributed to genetics and advanced age: administration of drugs such as anti-cancer chemotherapeutic drugs and contraceptives; topical use of chemical treatments, such as hair dyes, permanent wave solutions, and straighteners; diseases, such as leprosy or syphilis; illness; allergy; and hair follicle infection.
• Scarring alopecia may be a consequence of burns (accidental or post surgical from cryosurgery or laser surgery) or trauma, which often causes destruction of follicles.
• Androgenetic alopecia is a non-scarring hair loss of telogen hairs caused by an excessive androgen effect in genetically susceptible men and women. Androgens trigger the miniaturization or atrophy of terminal follicles that normally produce thick scalp hair and transforms them into vellus-like follicles, eventually yielding fine, downy hair that is barely perceptible. Androgenetic alopecia is expressed in males as baldness of the vertex of the scalp and is commonly referred to as male pattern baldness. In females, androgenetic alopecia appears as diffuse hair loss or thinning of the frontopa ⁇ etal areas.
• Androgenetic alopecia which is sometimes referred to as “common baldness” or “male pattern baldness,” independent of its causes, is the cutaneous aping of a particular zone (i.e., the scalp). Androgenetic alopecia can be defined, on one hand, as atrophy, sclerosis or minatu ⁇ zation of the hair follicles. On the other hand, androgenetic alopecia can be defined as a progressive shortening of the average duration of the anagen stage, which results in vellus hair prior to complete disappearance.
• Hair loss is an extremely common condition among healthy adult males, and also occurs frequently in adult females. In fact, some degree of alopecia on the vertex from puberty onwards is thought to be a universal phenomenon in both men and women (R. P R. Dawber (1987) Dermatologica 175:23-28). Alopecia is also frequently observed in both pre- and post-pubertal patients as a side effect of anti-cancer chemotherapy, (A. M. Hussein, et al. (1990) Science 249:1564-1566, B. W. Cline, (1984) Cancer Nursing, 7:221- 228; A. F: Hood (1986) Med. Clin. North Am. 70:187-209 ).
• minoxidil A common non-surgical treatment for stimulating hair growth is minoxidil (The Upjohn Company, Kalamazoo. Mich.).
• a solution of minoxidil as active ingredient is known as Rogaine.RTM.
• Rogaine.RTM As stated in the Rogame.RTM.
• Patient information Booklet The Upjohn Company, Kalamazoo, Mich., revised June, 1992
• minoxidil is a vasodilatory drug which has serious side effects when administered orally for the treatment of hypertension.
• topical application of minoxidil for the treatment of androgenetic alopecia is only partially effective and suffers from a number of disadvantages.
• minoxidil is only recommended for treatment of male pattern alopecia of the vertex (i.e., frontal recession), has to be applied twice daily for at least four months, and requires a normal scalp with no local abrasions, dermatitis or sunburn - conditions that can increase absorption into the blood stream and the concomitant risk of side effects.
• minoxidil is of limited effectiveness. For example, there is no significant increase in terminal hair regrowth between minoxidil and placebo treatment groups after four months of treatment (refer to the Rogame.RTM. Patient Information Booklet, The Upjohn Company, Kalamazoo. Mich., revised June, 1992 ). In patients who do respond to minoxidil treatment, the new hair is likely to be shed within a few months after stopping treatment.
• Androgens are responsible for many physiological functions in both males and females Androgen action is mediated by specific intracellular hormone receptors expressed in androgen responsive cells.
• Testosterone the major circulating androgen, is secreted by Leydig cells of the testes under the stimulation of pituitary-derived luteinizmg hormone (LH).
• LH pituitary-derived luteinizmg hormone
• DHT dihydrotestosterone
• Steroid ⁇ .alpha.-reductases in target tissues catalyze conversion of testosterone to DHT.
• isozyme specific and dual inhibitors of the two isozymes of ⁇ .alpha.-reductase will depend upon the type of disease treated (benign prostatic hyperplasia, prostate cancer, acne, male pattern baldness or hirsutism) as well as the stage of the disease (prevention versus treatment) and the anticipated side-effects in the intended patients (for example treatment of acne vulga ⁇ s in pubescent males).
• testosterone ⁇ . alpha - reductase inhibitors have been the subject of active research worldwide. For example, see: Hsia, S. and Voight, W., J. Invest. Derm., 62, 324 (1973); Robaire, B. et W., J. Steroid Biochem., 8. 307 (1977); Petrow, V. et al., Steroids, 38, 121 (1981); Liang. T. et al. J. Steroid Biochem., 19, 38 ⁇ (1983); Holt, D. et al., J. Med. Chem., 33, 937 (1990): U.S. Pat. No. 4.377, ⁇ 84, U.S. Pat. No.
• ⁇ .alpha.-reductase inhibitors are: (1) MK-906 (Merck), known by the generic name, finasteride, and marketed under the trademark, Proscar; (2) SKF-10 ⁇ 657 (SmithKhne Beecham); and (3) cyproterone acetate.
• Finasteride (17.beta.-(N-tert-butylcarbamoyl )-4-aza ⁇ . alpha. -androst-l-ene-3-one). which is marketed by Merck & Co., Inc. under the tradename PROSCAR. RTM.. is an inhibitor of ⁇ . alpha. -reductase 2 and is known to be useful for the treatment of hyperandrogenetic conditions. See e.g., U.S. Pat. No. 4,760,071. Finasteride is currently marketed in the United States and worldwide for the treatment of benign prostatic hyperplasia. Finaste ⁇ de's utility in the treatment of androgenetic alopecia is also disclosed in the following documents: EP 0 28 ⁇ ,382. published Oct. ⁇ , 1988; EP O 28 ⁇ 383, published Oct. ⁇ , 1988; Canadian Patent no. 1,302,277; and Canadian Patent no. 1,302.276.
• Androgens are the most obvious regulators of human hair growth in both sexes. Androgens have pradoxically contrasting effects on follicles depending on their location in the body. Androgens stimulate hair growth in many locations (i.e., beard, axilla) while inhibiting scalp hair growth in genetically predisposed individuals. Androgens act on the hair follicles via the dermal papilla, presumably by altering the production of regulatory factors effecting the dermal papilla cells. Cultured dermal papilla cells secrete soluble, protemaceous factors which are mitogenic for other dermal papilla cells, outer root sheath cells, epidermal keratinocytes and endothe al cells. Androgen sensitive cells from beard or balding scalp reflect their in vivo androgenetic responses by responding to testosterone, by increasing (i.e., beard) or decreasing (i.e.. balding) their mitogenic ability.
• the dermal papilla is a connective tissue structure situated at the base of hair follicles.
• the dermal papilla is composed of specialized fibroblast cells which demonstrate major changes in terms of cell morphology, vascula ⁇ zation, composition and volume of extracellular matrix.
• the dermal papilla cells show intracellular structures indicating on going protein synthesis and there is an active vascula ⁇ zation process, whereas during the telogen it is quiescent and non vascula ⁇ zed.
• the dermal papilla extracellular matrix contains collagen laminin fibronectin and haparin sulfate proteoglycan.
• the extracellular matrix diminishes in volume and in the telogen phase it is almost nonexistent.
• laminin and proteoglicans dirninwhile the collagen content is increased in the interfollicular dermis and in the dermal papilla.
• proteoglicans involvement in the hair growth process in addition to the above mentioned changed pattern of expression during the hair growth cycle. Injection of glycosamonoglycans in to skin of rabbits stimulated hair growth
• the accumulation of proteoglycans in the skin, like in pretibial myxedema is associated with hypert ⁇ chosis.
• the present invention relates to the use of Relaxin, in the manufacture of medicaments having a novel application, to a method of use in which relaxin is utilized for the treatment and prevention of certain conditions and to pharmaceutical compositions comprising relaxin.
• Relaxin otherwise known as Cervilaxitl, and formerly referred to as Releasin, is a polypeptide hormone secreted by the corpora lutes of many malian species during pregnancy.
• Releasin is a polypeptide hormone secreted by the corpora lutes of many malian species during pregnancy.
• relaxin is present in the ovaries of animals and may be extracted therefrom. It is believed to be a hormone of pregancy and has aroused great interest in the field of medical research.
• EP 08664g the contents of which are incorporated herein by reference, relates to the molecular cloning and characterization of the gene sequence coding for porcine relaxin.
• recombmant DNA techniques for the preparation of porcine relaxin were described more than ten years ago
• application of relaxin has been restricted essentially to pregnancy- and gynecologically-related uses.
• relaxin and relaxin analog compounds in combination with anti-androgenic agents i.e., relaxin plus finasteride, SKL-1056 ⁇ 7, estrogen, Cyproterone acetate, spironolactor, Flutamide, topical minoxidil 2%, topical minoxidil 5%, or RU ⁇ 8841.
• anti-androgenic agents i.e., relaxin plus finasteride, SKL-1056 ⁇ 7, estrogen, Cyproterone acetate, spironolactor, Flutamide, topical minoxidil 2%, topical minoxidil 5%, or RU ⁇ 8841.
• relaxin and relaxin analog compounds in combination with estrogenic hormones prevents hair loss in females.
• relaxin means human relaxin, including full length relaxin or a portion of the relaxin molecule that retains biological activity [as described in U.S. Pat. No. ⁇ , 023, 321, preferably recombmant human relaxin (H2)] and other active agents with relaxm-like activity, such as agents that competitively displace bound relaxin from a receptor.
• Relaxin can be made by any method known to those skilled in the art, preferably as described in U.S. Pat. No. 4,83 ⁇ ,2 ⁇ l or U.S. Pat. No. ⁇ ,811,39 ⁇ issued to Schwabe.
• H2 recombmant human relaxin
• the invention provides use of relaxin and relaxin analog compounds in combination with antiandrogenetic agents in the manufacture of a medicament for the treatment and prevention of androgenetic alopecia and related conditions (such as atrophy, sclerosis and miniaturization of the hair and hair follicles).
• the medicament may comprise the relaxin or relaxin analog compounds/ anitandrogenetic agent combination in a pharmaceutically acceptable (i.e., topically acceptable) carrier, and may be used, for example, for prolonging the duration of the anagen stage of hair growth.
• the invention provides a method for the treatment and prevention of androgenetic alopecia and related conditions, which comprises administering to a human in which said treatment or prevention is desired, an effective amount of relaxin or relaxin compounds.
• relaxin or relaxin compounds may be administered in combination with a pharmaceutically acceptable (i.e., a topically acceptable) carrier.
• the method may thus be used, for example, for the treatement and prevention of a condition selected from atrophy, sclerosis and miniaturization of the hair and hair follicles, or for prolonging the duration of the anagen stage of hair growth
• cyclic activity of the hair is divided into three stages: a period of active growth known as antigen, a short transition phase called catagen, and a resting period which ends in hair loss, called telogen.
• the object of the present invention is to decrease the activity of ⁇ .alpha.- reductase and increase the activity of aromatase.
• Aromatase is located specifically in the outer root sheath in active follicles in quantities 2- ⁇ times higher in women than in men.
• Cytokines are small proteins involved in cell to cell communication. They include peptide growth factors (i.e., EGF, IGF- 1, FGF's, NGF) and interlukms (i.e., ILI, IL2, TNF's). They have an important role in cell growth regulation and differentiation of many cell types, including skin fibroblast and keratmocytes. They act through specific cell surface receptors and they have fast, potent and local action. There are over ⁇ O or more known complex biological control systems.
• Cytokines act as (1) inhibitors of hair growth in vitro (i.e., TGF-BETA, ILI -ALPHA. ILI-BETA, TNF-ALPHA) and (2) modulators of catagen (i.e., KGF FGF).
• IGF-I maintains hair follicles in the anagen phase. The follicles enter catagen if IGF- 1 is absent. IGF-1 and IGF-I-R gene expression declines. TGF-BETA triggers the catagen phase. It is a potent inhibitor of hair growth in vitro. Relaxin increases IGF 1 and decreases TGF-BETA therefore it has the desired effect on hair growth and prevention of hair loss.
• ( I )w ⁇ ll have anti androgenetic effect, such as cyproterone acetate, spironolactor, Flutamide, all of which are useful for females, and topical minoxidil 2% and 5%, and all blockers of androgenetic receptors, such as
• Relaxin is a small polypeptide member of the protein hormone family, which also includes insulin and insulin like growth factors IGF-1 and IGF-2. Relaxin is expressed during pregnancy and research demonstrates that relaxin: (1) exerts a stimulatory synergistic effect on aromatase activity (anti-androgenetic effect) in human endomet ⁇ al stromal cells: (2) promotes growth of porcine granulosa cells by stimulation of IGF-1; (3) is a potent collagen down regulatory agent which interrupts collagen expression pretransitionally and at a point in the collagen induction pathway common to both TGF-BETA and ILI-BETA (two stimulators of collagen expression); (4) influences molecules of the extracellular matrix of connective tissue increasing the content of proteoglycans in rat uterus and cervix; ( ⁇ ) promotes synthesis of laminin in endothermal stromal cells in mice; (6) assists in the partial degradation of the fetal membrane extracellular matrix and causes activation of an enzyme cascade resulting in remodeling and changes in the structure of this complex
• the patterns of relaxin and relaxin binding cells indicates that in the hair follicles these patterns may act not only directly as mitogen on the germinative cells and on the outer root sheath, but also indirectly on the dermal papilla stimulating the production of growth factors.
• the binding cells of relaxin in the outer root sheath indicate that relaxin may play a role in regulating terminal differentiation.
• Relaxin influences the fibroblasts and fibroblast- 1 ike cells of the pilosebacious unit. Relaxin treatment, either topically or systemically, will result in preventing atrophy, sclerosis and minatu ⁇ zation of the hair, by prolonging the duration of the anagen stage, or otherwise. It will remodulate the cutaneous aging process in general and in particular it will remodulate androgenetic alopecia in both males and females.
• compositions which can be applied topically in the form of lotion, ointment, gel or cream, or systemically for internal or parenteral use, in the form of capsules, tablets or ampules, for treatement of androgenetic alopecia and related conditions such as alopecia areata, anagen effluvium, telogen effuvium and post-partum telogen alopecia, diffuse alopecia, and alopecia androgenetica.
• compositions can be in the form of lotions, ointments, gels or creams, prepared for use in any conventional manner, in admixture with one or more physiologically acceptable carriers and diluents.
• compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain agents such as emulsifying, suspending, stabilizing, gelling and/or dispersing agents.
• the active ingredients may be in powder form for constitution with a suitable vehicle (i.e., sterile, pyrogen-free water) before use and may compounded into tablet, powder or capsule form using techniques well known to those skilled in the formulary art.
• the formulations of the present invention comprise at least one active ingredient, as above defined, together with one or more acceptable carriers therefor and optionally other therapeutic ingredients.
• the carr ⁇ er(s) must be acceptable in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.
• the formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. Such methods include the step of bringing into association the active ingredient with the carrier, which constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers, or both, and then, if necessary, shaping the product.
• the formulations are preferably applied as a topical lotion, ointment, gel or cream, containing the active ingredient in a concentration of, for example, 0.005 to 10.0 percent, preferably 0.01 to 5.0 percent w/w and most preferably 0.05 to 2.0 percent w/w.
• the active ingredients may be employed with an oil-in-water cream base.
• the aqueous phase of the cream base may include, for example, at least thirty percent ( 30% ) w/w of a polyhyd ⁇ c alcohol (i.e., an alcohol having two or more hydroxyl groups such as propylene glycol, butane- 1,3-d ⁇ ol. Mannitol, sorbitol, glycerol and polyethylene glycol and mixtures thereof.
• the topical formulations many desirably include a compound which enhances absorption or penetration of the active ingredient through the skin or other affected areas. Examples of such dermal penetration enhancers include dimethylsuiphoxide and related analogues.
• the oily phase of the emulsions of this invention may be constituted from known ingredients in a known manner.
• the oil phase may comprise merely an emulsifier it desirably comprises a mixture of at least one emulsifier with a fat or an oil or with both a fat and an oil.
• a hydrophi c emulsifier is included together with a lipophi c emulsifier, which acts as a stabilizer. It is also preferred to include both an oil and a fat.
• the emuls ⁇ f ⁇ er(s), with or without stab ⁇ l ⁇ zers(s), make up the so-called emulsifying wax, and the wax, together with the oil and/or fat, make up the so-called emulsifying ointment base, which forms the oily dispersed phase of the cream formulations.
• Emulgents and emulsion stabilizers suitable for use in the formulation of the present invention include Tween 60. Span 80, cetostearyl alcohol, my ⁇ styl alcohol, glycerl monostearate and sodium lauryl sulphate.
• the choice of suitable oils or fats for the formulation is based on achieving the desired cosmetic properties, because the solubility of the active compound in most oils likely to be used in pharmaceutical emulsion formulations is very low. Therefore, the cream should preferably be a non-greasy, non-staining and washable product with suitable consistency to avoid leakage from tubes or other containers.
• Straight or branched chain, mono- or dibasic alkyl esters such as di-isoadipate, isocetyl stearate, propylene glycol diester or coconut fatty acids, isopropyl my ⁇ state, decyl oleate, iso- propyl palmitate, butyl stearate, 3-ethylhexyl palmitate, or a blend of branched chain esters known as Crodamol CAP may be used, the last three being preferred esters. These may be used alone or in combination, depending on the properties required. Alternatively, high melting-point lipids, such as white soft paraffin and/or liquid paraffin, or other mineral oils, can be used.
• the Relaxin and anti-adnogenetic agent were dissolved in the mixture of solvents.
• the Relaxin was dissolved in the water/alcohol mixture.
• the carbomer was dispersed in the solution and the t ⁇ ethanolainine was added while agitating constantly.
• the Relaxin and HPMC were dissolved in the water and the alcohol was added.
• the carbomer was dispersed in the solution and tnethanolamme was added while agitating.
• the Relaxin and minoxidil and HPMC were dissolved in the water and the alcohol was added.
• the carbomer was dispersed in the solution and the tnethanolamme was added while agitating.
• the Relaxin, potassium sorbate, and glycerol were dissolved in water and the carbomer was dispersed in the solution, at room temperature.
• the cetylester wax, polysorbate and paraffin oil were heated to dissolve, and were mixed with the aqueous portion at room temperature. Ammonia was added to gel the carbomer.
• the Relaxin and the polyvinylpytrohdone were dissolved in a quantity of deionized water and the lactose and sodium starch glycollate were granulated in accordance with normal procedure. The granulation was dried and the magnesium stearate added. The mixture was compressed into tablets.
• the ingredients were dissolved in the water for injection and the solution sterilized by filtration.
• the ampoules were filled and sealed under aseptic conditions
• a suitable non-toxic medium i.e., silicon polymer

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Epidemiology (AREA)
• Birds (AREA)
• Medicinal Chemistry (AREA)
• Chemical & Material Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Engineering & Computer Science (AREA)
• Endocrinology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Zoology (AREA)
• Gastroenterology & Hepatology (AREA)
• Immunology (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Dermatology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Cosmetics (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Priority Applications (3)

Applications Claiming Priority (2)

Publications (1)

Family

ID=23366490

Family Applications (1)

Country Status (4)

Cited By (4)

Families Citing this family (1)

Citations (3)

Family Cites Families (5)

• 2000
  • 2000-07-03 CA CA002378598A patent/CA2378598A1/en not_active Abandoned
  • 2000-07-03 EP EP00938984A patent/EP1154783A4/de not_active Withdrawn
  • 2000-07-03 AU AU54199/00A patent/AU771256B2/en not_active Ceased
  • 2000-07-03 WO PCT/IB2000/000901 patent/WO2001001997A1/en active IP Right Grant

Patent Citations (3)

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events