CN101405023A - Collagenase for treating cellulite - Google Patents
Collagenase for treating cellulite Download PDFInfo
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- CN101405023A CN101405023A CNA2007800098239A CN200780009823A CN101405023A CN 101405023 A CN101405023 A CN 101405023A CN A2007800098239 A CNA2007800098239 A CN A2007800098239A CN 200780009823 A CN200780009823 A CN 200780009823A CN 101405023 A CN101405023 A CN 101405023A
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- collagenase
- purification
- liparitosis
- injected
- injection
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Classifications
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- 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)
- A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
-
- 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
- A61K8/66—Enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/06—Preparations for care of the skin for countering cellulitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/91—Injection
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- 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)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Dermatology (AREA)
- Birds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention relates to the discovery that collagenase injections are effective in dissolving and lysing the collagenous septa network in the skin which comprises cellulite. As such, the invention relates to methods of treating cellulite in a patient in need of such treatment comprising injecting or otherwise delivering the effective amount of purified collagenase to the collagenous septa network of cellulite in the skin. The invention also relates to the use of collagenase in the manufacture of a medicament to treat cetlulite of the skin.
Description
Priority
The application requires to enjoy the priority that application serial no is 60/775690 application, and above-mentioned application is filed an application to United States Patent (USP) trademark office on February 22nd, 2006.
Government supports
The present invention has obtained the part support of the M01RR10710 number appropriation of national institute of health (the National Institutes ofHealth).U.S. government enjoys some right of the present invention.
Background technology
" ground effect phenomenon (the mattress phenomenon) " of the dimpling of skin (dimpling) or thigh and buttocks is commonly referred to as liparitosis.This symptom is very general, and appears among the different healthy individual, compares with the male, and this symptom is more frequent is tormenting the women.There is a large amount of OTC (over-the-counter) topical therapeutics at present, is used for eliminating liparitosis.Verified these products and other OTC (over-the-counter) topical therapeutic agent is invalid, cost is high, and in fact never pass through the placebo clinical research.Recently to local retinol and contain caffeine and randomization placebo-controlled trial that the retinol of spiral shell Ke Jining carries out proves that equally it fails to show the value of eliminating liparitosis.
In the treatment of liparitosis, achieve success if desired, so then need this kind symptom is carried out clear and definite basic pathology physiology definition.The definition of this symptom only is recorded in the morphology of liparitosis being carried out by people such as Rosenbaum in 1999 and biochemistry investigation (referring to Rosenbaum, M.Prieto, V., Hellmer, J., Boschmann, M., Krueger, J., Leibel, R.L., Ship, A.G. in 1998 at Plastic﹠amp; ReconstSurg 101 (7): the article of delivering among the 1934-9
An Exploratory Investigation of The the Morphology and Biochemistry of Cellulite " shape that liparitosis is carried out Attitude and biochemistry are surveyed sex investigation ")Among the adult respondent of seven health, two male of five women, wherein four infected above-mentioned symptom and three do not infect above-mentioned symptom, they have accepted metabolic regional the detection and the huckle through thickness wedge shape biopsy through carrying out after the local anesthesia of subcutaneous fatty tissue in the ultrasound investigation, body of huckle.The existence of liparitosis is defined as the significantly dimpling phenomenon of thigh place, the outside, back skin.In any continuum of at least 3 cm diameters of skin, do not exist tangible dimpling phenomenon then to mean there is not infection symptoms.All individualities that infected symptom are studied, comprised the zone of infecting in its leg portion and do not infect.Sound spectrograph inspection in the body of the microscopy of described wedge shape biological tissue and leg portion is all shown: in the subject of infection symptoms, intrinsic fatty tissue generation dispersion shape extrude and arrive retinaculum skin, and in the subject that does not infect, do not observe this phenomenon.Above-mentioned research also shows, in the women, have irregular scattering type and discontinuous connective tissue under skin, and in the male, same connective tissue layer is level and smooth and successive.Compare with the individuality that does not infect, this connective tissue layer in the individuality that is infected is more irregular and discontinuous.Do not observing marked difference aspect subcutaneus adipose tissue form, lipolytic response or the regional blood flow of infected individual and uninfection individuality.This studies show that, has sex dimorphism (sexual dimorphism) on the architectural feature of skin connective tissue, and the women is more prone to form the irregular of fatty tissue and extrudes in skin, and this extruding is defined as liparitosis.The conclusion that this research draws is: do not have clear evidence to show that fatty tissue physiology, blood flow or fatty tissue biochemistry play any significant feature in the etiology of liparitosis, but the structure of the connective tissue on women's thigh and the buttocks has been emphasized the difference on little subcutaneus adipose tissue deposition.
This conclusion has obtained confirmation in people's such as Pierard paper, people such as Pierard to 39 obduction samples carried out microscopically inspection (referring to Pierard-Franchimont, C., Pierard G.E., Henry, F., Vroome, V.﹠amp; Cauwenbergh, people such as G. in 2000 in Amer.J.Clin.Dermatology " U.S.'s clinical dermatology magazine ", 1 (6): the article of delivering among the 369-74
A Randomized, Placebo-Controlled Trial of Topical Retinol in the " Huang is looked in the part of carrying out in to the therapeutic process of liparitosis to Treatment of Cellulite Alcohol randomization, placebo-controlled trial ").The matched group that they use is made up of four adult females and 11 adult males, and there is not tangible liparitosis in described matched group.They claim: as if the interfacial caking outward appearance of dermis of skin (lumpy aspect) shows at described thigh and buttocks position has a kind of characteristic that is associated with sex (women).The observed this ground effect phenomenon of microscopically (mattressphenomenon) is regarded as liparitosis, and present the fibrosclerosis chain (fibrosclerotic strands) that focus enlarges, described subcutaneous tissue is cut apart.What they inferred that such structure may represent is the reactive process of keeping the corium pressure that is caused by the accumulation of fat.
In the middle of the research of being undertaken by people such as Querleux more a little later, utilize in the body magnetic resonance imaging and spectrum that subcutaneus adipose tissue has been carried out anatomy and Physiologic Studies (referring to Querleux at the appearance of sex and liparitosis, B., Cornillon, C., Jolivet, O., Bittoun, J. are published in Skin Research AndTech " skin research and technology " 8 (2) in May, 2002: the article among the 118-124
Anatomy and Physiology of Subcutaneous Adipose Tissue by in vivo Magnetic Resonance Imaging and Spectroscopy:Relationship with sex and Presence of Cellulite is " by magnetic resonance imaging in the body and spectrum to subcutaneous fat Anatomy that the fat tissue carries out and Physiologic Studies: with the related and liparitosis of sex Appearance ").The conclusion that these authors draw is: suffering from the middle of the women of liparitosis, to fibroid at interval the 3D that carries out of network be reconstituted in the interval (septae) that shows higher percentage composition on the direction perpendicular to skin surface.
Up to today still not at the effective Therapeutic Method of liparitosis.The object of the present invention is to provide such method, be used to carry out the treatment of liparitosis.
Summary of the invention
The present invention relates to following discovery: the ossein that the collagenase injection can effectively dissolve body fat group is network (septa network) at interval, thus the liparitosis of treatment and reappear slick skin appearance.The patient who the present invention relates to needs are received treatment carries out the treatment of liparitosis, comprises the collagenase to the purification of patient infusion effective dose, and the collagenase of described purification is made into to be used for the treatment of the medicine type of liparitosis.Described collagenase is preferably purified, and does not contain other enzyme in essence, for example protease and/or hyaluronidase.
The specific embodiment
The present invention relates to following discovery: the ossein that the collagenase injection can effectively dissolve body fat group is network (septa network) at interval, thus the liparitosis of treatment and reappear slick skin appearance.The patient who the present invention relates to needs are received treatment carries out the treatment of liparitosis, comprises to patient's the thigh and/or the collagenase of buttocks injection effective dose.The invention still further relates to the purposes of collagenase in the preparation medicament, wherein said medicament is used for the treatment of liparitosis.
The collagenase injection has been proposed to be used for treating some disease, dupp Yi Telunshi disease (Dupuytren ' s disease) for example, and adhesive synovitis, and send Ni Ershi disease (Peyronie ' s disease).These diseases all relevant with ossein sheath (collagen cord) or ossein speckle (collagen plaque) (referring to Wegman, the US Patent No 5589171 of Thomas.L., the applying date of this patent is December in 1996 31 days; US Patent No 6086872, the applying date of this patent is on July 11st, 2000; US Patent No 6022539, the applying date of this patent is on February 8th, 2000, the patent-adhesive synovitis of not winding up the case, the full content of above-mentioned document is hereby incorporated by).
The collagenase injection also is proposed to be used for treating liparitosis, prerequisite is to be used in combination (referring to Pinelle with hyaluronidase, a kind of lyoenzyme product of preparing from the mammal testis, the US Patent No 4645668 of Sheldon R., the applying date of this patent is on March 27th, 1985).Above-mentioned patent disclosure a kind of embodiment that is used for the treatment of liparitosis, use the collagenase (100 unit) of few dosage and hyaluronidase (150 unit) together to use, and only at female patient.After above-mentioned injection occurs, in the improvement that does not have aspect the treatment of liparitosis on the further details.
Verified, use the clostridium histolyticum collagenase of purification to carry out intralesional (intralesional) injection and have the clinic safety, and deformity is rolled up in the bending that can effectively correct hand in the clinical trial of dupp Yi Telunshi disease.In addition, the clostridium histolyticum collagenase of use purification carries out capsule outer (extracapsular) injection and also shows the clinic safety, and in the clinical trial of treatment adhesive synovitis (congealed shoulder), can effectively reduce, above-mentioned injection also is used to send the clinical trial of Ni Ershi disease by other people, the described Ni Ershi of group disease is the deformity of rolling up of penis.
The paper that the present inventor doctor Badalamente is delivered about dupp Yi Telunshi disease constituted ultimate principle of the present invention (referring to Starkweather, K., Lattuga, S., Hurst, L.C., Badalamenta, M.A., Guilak, F., Sampson, S.P., Dowd, A., Wisch, the article that D. was published among J.Hand Surg. " the hand surgical operation magazine " 21A:490-95 in 1996
Collagenase in the Treatment Of Dupuytren ' s Disease:An in vitro Study " uses collagenase treatment dupp Yi Telunshi disease a: in vitro study "Badalamente, M.A., Hurst, L.C. were published in J.Drug-Delivery " drug conveying magazine " 3 (1) in 1996: the article among the 35-40
Enzyme Injection as a Non-operative Treatment for Dupuytren ' s Disease " use the enzyme injection to dupp Yi Telunshi disease carry out in This Ke Shi therapy "Hurst, L.C., Badalamente, M.A. (specially inviting the author) were published in Hand Clinics " hand clinic " in 1999, G.M.Rayan (editor) .W.B.Saunders 15 (1), the article among the 97-107
Non-operative Treatment for Dupuytren ' s Disease " to dupp Yi Telunshi disease carry out interior this Ke Shi therapy "Hurst, L.C., Badalamente, M.A. (specially invites editor ﹠amp; The author) article of delivering in 2000
Dupuytren ' s Disease " dupp Yi Telunshi disease ", R.Tubinana, R.Tubiana, C.Leclercq, L.C.Hurst, M.A.Badalamente (editor), Martin Dunitz publishing house, London; Badalamente, M.A., Hurst, L.C. were published in J.Hand Surg. " hand surgical operation magazine " 25A (4) in 2000: the article among the 629-36
Enzyme Injection as a Non-operative Treatment For Dupuytren ' s Disease " uses the enzyme injection that dupp Yi Telunshi disease is carried out Non-operative treatment "Badalamente, M.A., Hurst, L.C., Hentz, V.R. were published in J.Hand Surg. " hand surgical operation magazine " 27A (5) in 2002: the article among the 788-98
Collagen as a Clinical Target:Non-operative Treatment For Dupuytren ' s Disease is " with ossein as clinical target: to dupp Yi Telun The non-operative treatment that family name's disease is carried out ").In dupp Yi Telunshi disease, the fibrous sheath of special disease is put the arrangement of the interval sample that is embroidered with fatty tissue usually.This phenomenon shows as " caking " of the air cushion shape of different sizes clinically, in dupp Yi Telunshi disease, is referred to as the joint knot.Second phase test and the test of three phases at dupp Yi Telunshi disease have drawn corresponding to clinical discovery, that is: after the clostridium histolyticum collagenase through the injection purification, when being subjected to the pressure of bearing of trend, be not only that described collagen sheath disappears molten and fracture, dissolving and harmless absorption more also take place in fiber-fat joint knot.Therefore, to be estimated to be in the liparitosis zone be safe with being injected under the collagenase percutaneous, and can effectively treat this symptom, reappears the smooth appearance of thigh and/or skin of buttock.
Collagenase is a kind of enzyme with specificity ability of digestion ossein.A kind of preferred form of collagenase comes from the fermentation of clostridium histolyticum, and use chromatographic technique to carry out purification afterwards, be that the series number on January 20th, 2006 is a disclosed content (AttorneyDocket Number 40243001 US) in the U. S. application of No.60763470 referring to the applying date for example, the full content of above-mentioned application is hereby incorporated by.By the naturally produced collagenase of clostridium histolyticum in case through purification, when using electrophoresis SDS (120,000 and sodium sulfonate) when gel carries out electrophoresis, will present two distinct peaks.Above-mentioned two distinct peaks are referred to as collagenase I and collagenase II.
The collagenase powder of aseptic freeze-dried form can commercially be bought and obtain, and has the minimum dfetectable quantity (minimum assay) of every milligram 50 unit.Described detection limit can according to batch do not coexist and be higher than in the suitable scope of above-mentioned numerical value, but when together being used for preparing the aimed concn that is used for the treatment of with the acceptable carrier of a kind of medicine, it need be taken into account when determining described powder weight, the acceptable carrier of wherein said medicine for example is common saline.
Place the acceptable liquid-carrier of medicine to use described collagenase, the acceptable liquid-carrier of described medicine is inert for described collagenase.The example of carrier is common saline, liquid sodium chloride/calcium chloride buffer, liquid dextran solution, liquid hydroxyethyl starch solution.
A kind of form as the collagenase of the purification of injection is made up of two kinds of microbiological Collagenase, and they are called as " Collagenase A BC I " and " Collagenase A BC II ".Above-mentioned two kinds of collagenases all are that separated and purification comes out from the sweat of clostridium histolyticum antibacterial, and belong to identical metalloproteases.
Collagenase A BC I is an independent polypeptide chain, and described polypeptide chain is made of the aminoacid of about 1000 known arrays.Observe, it has 115kiloDalton (kilodalton, molecular weight kD), the isoelectric point, IP within the 5.63-5.68 scope (pI) and 1.480 extinction coefficient.Can determine that for the active behavior of synthetic substrate Collagenase A BC I is an I class clostridium histolyticum collagenase alleged in the prior art document by it.
Collagenase A BC II also is an independent polypeptide chain, and described polypeptide chain is made of the aminoacid of about 1000 derivation sequences.Observe, it has the molecular weight of 110kD, isoelectric point, IP within the 5.46-5.57 scope and 1.576 extinction coefficient.Collagenase A BC II belongs to II class clostridium histolyticum collagenase alleged in the prior art document on function.
Can contain in the described medical substance with blended Collagenase A BC-I of 1: 1 mass ratio and Collagenase A BC-II, it has 1.528 extinction coefficient.In order to keep active, two kinds of collagenases zinc and loose that all needs to combine closely in conjunction with calcium.There are not the cross reactivity on the immunology in Collagenase A BC I and Collagenase A BC II, and all have very wide in range hydrolytic reactivity for all types of osseins.Although every kind of collagenase shows different specificitys, they produce synergistic activity to ossein jointly.
The freeze-dried type collagenase that is used for injection is the clostridium histolyticum collagenase of the purification for preparing as lyophilising composition, and can contain a Lactose hydrate of about 0.1 milligram USP grade in the collagenase activity of per 1000 ABC units.
A kind of preferred collagenase compositions comprises the mixture of collagenase I and collagenase II, both mass ratioes are approximately 1: 1, and have the activity specific of about 500SRC unit/milligram to about 15000SRC unit/milligram, preferably has at least approximately activity specific of 700SRC unit/milligram, more preferably have at least approximately activity specific of 1000SRC unit/milligram, even more preferably have at least approximately activity specific of 1500SRC unit/milligram.Under 25 ℃, the condition of pH 7.4, the amount that SRC unit's per minute can dissolved Mus tail collagen is equivalent to 1 in the ninhydrin reaction material and receives the leucine that rubs.Also can use ABC unit that collagenase is described.To the detection of tiring (potency assay) of collagenase is that digestible degree with not degeneration ossein (coming from the cattle heel string) under the condition of 7.2,37 ℃ of pH and 20-24 hour is a foundation.By reacting, thereby measure the quantity of the peptide bond of fracture with 1,2,3-indantrione monohydrate.Deduct the amino group that dissolving digestion matched group discharges.The Collagenase A BC unit per minute of a remainder (net) is equivalent to 1.09 with dissolved ninhydrin reaction raw material and receives the leucine that rubs.A SRC unit approximates 6.3 ABC units.
Described collagenase preferably is present in the acceptable liquid-carrier of a kind of medicine to be used via injection.Preferably, described carrier does not react to each other with described collagenase, and described collagenase is lost activity.The example of carrier is common saline, liquid sodium chloride/calcium chloride buffer (containing 0.9% sodium chloride and 2 calcium chloride that rub in the least).For example, in the compositions of lyophilized form, can contain a Lactose hydrate of 0.1 milligram in every 1000ABC unit.Below contain the collagenase of 5150ABC unit in employed each vial.
According to the present invention, will be present in the liparitosis zone at thigh place, the back outside that collagenase in the liquid-carrier is injected to the patient.The dosage of employed collagenase and concentration are the dosage and the concentration of the collagen interval network in the effective dissolving (lyse) and molten (dissolve) the described liparitosis that disappears.
Described injection is aseptic, and can be above 1.0 milliliters.Above-mentioned whole dosage is injected in the thigh of the outside, described back by five different points, and the liparitosis dimpling phenomenon of thigh is the most obvious in above-mentioned zone.Its target is to guarantee that described collagenase forms good distribution.The patient preferably relies on the thigh of opposite side to lie up about one hour, preferably has a rest two hours or the longer time.
In other embodiment, can the described collagenase of local application, for example, use in the liparitosis zone via transdermal patch or local cream or local ointment, perhaps can use via the mode of implanting, for example, slow (over time) discharges the microcapsule or the microsphere of collagenase.
In one embodiment, described patient is characterised in that at thigh place, the outside thereafter and has the liparitosis of one at least 10 * 10 cm section.The present invention can reach following improvement: the liparitosis of one at least 10 * 10 cm section that thigh place, the outside has after making is reappeared normal and slick skin appearance.
In another embodiment of the present invention, can the described collagenase of local application, for example, use in the liparitosis zone via transdermal patch or local cream or local ointment, perhaps can use via the mode of implanting, for example, slowly (overtime) discharges the microcapsule or the microsphere of collagenase, and is to use under the condition that does not have fluorine hydroxyl dehydrogenation cortex (steroid) alcohol or other corticosteroid.
When effect that single treatment produced is not enough, can be that interval repeats identical step, uses identical collagenase accumulated dose and concentration with 4-6 week.Liparitosis zone except the thigh of the outside, back also may need to treat, and is that interval repeats treatment with 4-6 week perhaps.For example, the front end of thigh and buttocks also may contain the liparitosis zone.
Embodiment
Method
Ten patients have participated in described project, all are the women, mean age 41=10 year.Average weight index (BMI) is 28.
The Minimum Area of the liparitosis that above-mentioned patient's thigh place, the back outside need comprise is 10 * 10 centimetres.All patients liparitosis zone that the thigh place has outside thereafter is all above 10 * 10 centimetres minimum zone.For carrying out baseline Digital photographic (baseline digital photograph) in above-mentioned zone of receiving treatment.With aseptic form 10000 ABC units (0.58 milligram) are injected in described 10 * 10 centimetres target liparitosis zone by five points.Whole fluid volumes of above-mentioned injection are 1.0 milliliters.The buffer that uses is aseptic 0.9% sodium chloride and 2 calcium chloride that rub in the least.In all patients first day after accepting injection, first week, first moon, the 3rd month and six month is mobile (flowed).After receiving treatment, it is carried out successive taking pictures.
In order to reach the symmetry on the cosmetology, when arriving the interval in 4-6 week after the patient is through collagenase injection for the first time, they can be chosen in opposed side edges and also carry out similar collagenase injection.By visual inspection and image file the effect of the degraded/elimination of the liparitosis in the target area at thigh place is judged.
In described 10 * 10 centimetres targeted treatment area, the target area of described liparitosis of receiving treatment is divided into quarter.By the degraded/elimination to the liparitosis in the described targeted treatment area quantizes to the visual inspection in above-mentioned equal portions zone, for example, 4/4=does not have the equal portions zone that treatment is responded; Three equal portions zones of 3/4=respond treatment; Two equal portions zones of 2/4=respond treatment; Equal portions zone of 1/4=responds treatment; All equal portions zones of 0/4=respond treatment.Need simultaneously the cms of the actual area of the liparitosis that still exists in the target liparitosis zone, the described back outside is measured.Simultaneously also use image to carry out filing of file.
The result
All patients have all experienced the degraded of the liparitosis at target thigh place after accepting the collagenase injection.Table 1 has been expressed the degradation results of the liparitosis in each equal portions at thigh place of the patient who receives treatment.The degraded of significant liparitosis has appearred in the zone of accepting injection.Compare with baseline, the liparitosis zone has degraded 77% in first day.This result has kept one longer period.Compare with baseline, the liparitosis zone has degraded 74% when a week, and the liparitosis zone has degraded 89% in the time of one month, and the liparitosis zone has degraded 86% in the time of three months, and the liparitosis zone has degraded 76% in the time of six months.
The adverse events (adverse events) that comprises tenderness, cicatrix and slight edema in the above-mentioned injection areas has well been solved in the processing mode of the 10th day, the 18th day and the 6th day respectively.
| Patient # LY C-009 | Age 37 | Sex women | The thigh right side | Parameter Body Mass Index girth (centimetre) area (centimetre) umber | Baseline 33 68 12,*14 4 | The first round is 33 68 12,*14 4 one day after | A week 34 68 5*5 2 after the first round | After the first round January 34 68 5*5 2 | After the first round March 34 68 5*5 2 | After the first round June 36 69 8*9 |
| Patient #NW C-001 | Age 52 | Sex women | The thigh right side | Parameter Body Mass Index girth (centimetre) area (centimetre) umber | Baseline 32 68 16,*12 4 | The first round is 31 66 2*2 1 one day after | A week 31 64 5*5 2 after the first round | January 31 64 00 after the first round | After the first round March 32 64 5*1 1 | After the first round June 32 64 5*1 1 |
| Patient # NW C-001 | Age 52 | Sex women | The thigh left side | Parameter Body Mass Index girth (centimetre) area (centimetre) umber | Baseline 32 68 19,*19 4 | Second takes turns 32 68 19,*19 4 one day after | Second takes turns one week of back, 32 69 5*5 2 | Second takes turns back January 32 66 00 | Second takes turns back 4*0 1 in March 31 63 | Second takes turns back June 30 63 00 |
| Patient # PD C-004 | Age 44 | Sex women | The thigh left side | Parameter Body Mass Index girth (centimetre) area (centimetre) umber | Baseline 24 57 10,*10 4 | The first round one day after 24 65 00 | A week 25 66 00 after the first round | After the first round January 24 63 4*3 1 | After the first round March 25 56 4*3 1 | After the first round June 25 56 4*3 1 |
| Patient # PD C-004 | Age 44 | Sex women | The thigh right side | Parameter Body Mass Index girth (centimetre) area (centimetre) umber | Baseline 25 60 10,*10 4 | Second takes turns one day after 25 62 00 | Second takes turns one week of back, 25 62 1*4 1 | Second takes turns back January 25 62 00 | Second takes turns back March 25 62 00 | Second takes turns back June |
| Patient # AP C-012 | Age 54 | Sex women | The thigh right side | Parameter Body Mass Index girth (centimetre) area (centimetre) umber | Baseline 23 56 10,*11 4 | The first round is 23 56 3*9 2 one day after | A week 23 56 3*5 1 after the first round | After the first round January 23 52 5*4 1 | Lose and visit bias (lost to follow up) March after the first round | June after the first round |
| Patient # ER C-015 | Age 44 | Sex women | The thigh left side | Parameter Body Mass Index girth (centimetre) area (centimetre) umber | Baseline 22 51 10,*10 4 | Second takes turns 22 54 5*9 2 one day after | Second takes turns one week of back, 22 52 4,*10 3 | Second takes turns back January 22 53 00 | Second takes turns back March 21 53 00 | Second takes turns back June |
| Patient # AE C-016 | Age 40 | Sex women | The thigh right side | Parameter Body Mass Index girth (centimetre) area (centimetre) umber | Baseline 31 67 12,*12 4 | The first round one day after 31 79 00 | A week 31 72 9*5 3 after the first round | After the first round January 31 69 2*3 1 | After the first round March 31 68 2*7 | After the first round June 30 64 2*7 2 |
| Patient # AE C-016 | Age 40 | Sex women | The thigh left side | Parameter Body Mass Index girth (centimetre) area (centimetre) umber | Baseline 31 69 12,*14 4 | Second takes turns one day after 31 71 00 | Second takes turns one week of back, 31 68 2*4 1 | Second takes turns back 1*2 1 in January 31 68 | Second takes turns back March 31 68 00 | Second takes turns back June |
| Patient # MM C-017 | Age 27 | Sex women | The thigh right side | Parameter Body Mass Index girth (centimetre) area (centimetre) umber | Baseline 37 74 14,*14 4 | The first round one day after 37 74 00 | A week 37 74 1,*10 2 after the first round | After the first round January 37 74 6*3 1 | Lose and visit bias (lost to follow up) March after the first round | June after the first round |
Seen the remarkable improvement of the degradation effect of the liparitosis at thigh place, the outside thereafter on one's body the patient who has accepted the collagenase injection.This studies show that it is a kind of safety and effective method that the collagenase injection is carried out in the liparitosis zone.
Preferred embodiment carried out specific expression and description although the present invention is directed to, those skilled in the art can understand, under the condition that does not deviate from by accompanying Claim institute restricted portion, can carry out various changes to form and details.
Claims (16)
1. method that the patient that needs are received treatment carries out the treatment of liparitosis, this method comprise the collagenase of carrying the purification of effective dose to described liparitosis collagenase at interval in the network.
2. method according to claim 1, wherein said collagenase (clostridiopeptidase) comes from the clostridium histolyticum antibacterial.
3. method according to claim 1, the collagenase of wherein said purification is used separately.
4. method according to claim 1, the collagenase of wherein said purification are to use under the condition that does not have triamcinolone or other corticosteroid.
5. method according to claim 1, wherein said purification of collagenases are to comprise that at least approximately the dosage of 700SRC unit is injected, to carry out once or once above injection.
6. method according to claim 1, the collagenase of wherein said purification are to comprise that at least approximately the dosage of 1000SRC unit is injected, to carry out once or once above injection.
7. method according to claim 1, the collagenase of wherein said purification are to comprise that at least approximately the dosage of 1500SRC unit is injected, to carry out once or once above injection.
8. method according to claim 1, the collagenase of wherein said purification are to comprise that at least approximately the dosage of 10000ABC unit is injected, to carry out once or once above injection.
9. method according to claim 1, the injected dose of the collagenase of wherein said purification are about 1.0 milliliters.
10. method according to claim 1, the collagenase of wherein said purification is injected by a plurality of sites.
11. method according to claim 1, the collagenase of wherein said purification is made up of collagenase I and collagenase II.
12. method according to claim 9, wherein described injection being delivered to skin dimpling phenomenon is in the liparitosis zone of feature.
13. method according to claim 1, wherein said patient is a human patients.
14. method according to claim 1 wherein repeats above-mentioned treatment at about 4-6 after week.
15. method according to claim 1, wherein during one month after accepting the using of at least collagenase, described patient tangible visual reducing occurred in appearance liparitosis.
16. method according to claim 1, the collagenase of wherein said purification are to comprise that at least approximately 500SRC unit/milligram to dosage of 15000SRC unit/milligram is injected, carried out once or multiple injection.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US77569006P | 2006-02-22 | 2006-02-22 | |
| US60/775,690 | 2006-02-22 | ||
| US11/703,269 | 2007-02-07 |
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| Publication Number | Publication Date |
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| CN101405023A true CN101405023A (en) | 2009-04-08 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNA2007800098239A Pending CN101405023A (en) | 2006-02-22 | 2007-02-22 | Collagenase for treating cellulite |
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|---|---|
| CN (1) | CN101405023A (en) |
| WO (1) | WO2007100590A2 (en) |
| ZA (1) | ZA200807221B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104603616A (en) * | 2012-09-07 | 2015-05-06 | 株式会社资生堂 | Method of evaluating cellulite and method of evaluating cellulite-effective drug using fibulin-3 and/or sarcoglycan gamma as an indicator |
| CN113015514A (en) * | 2018-09-18 | 2021-06-22 | 恩多全球美学有限公司 | Compositions and methods for treating subcutaneous cellulite |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| ES2968836T3 (en) | 2012-01-12 | 2024-05-14 | Endo Global Ventures | Clostridium histolyticum enzyme |
| ES2426017B1 (en) * | 2012-03-29 | 2014-09-17 | Proteos Biotech S.L. | Microemulsion comprising collagenase and uses |
| IL301796A (en) | 2017-03-01 | 2023-05-01 | Endo Ventures Ltd | Method for assessing and treating cellulite |
| WO2018183582A2 (en) | 2017-03-28 | 2018-10-04 | Endo Ventures Limited | Improved method of producing collagenase |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US4645668A (en) * | 1983-08-04 | 1987-02-24 | Biospecifics, Nv | Method for the prevention and treatment of scars with enzymes |
| US4524065A (en) * | 1983-08-04 | 1985-06-18 | Bio-Specifics N.V. | Method for the prevention and treatment of scars with enzymes |
| AU738512B2 (en) * | 1997-10-03 | 2001-09-20 | Lavipharm Laboratories, Inc. | A prolamine-plant polar lipid composition, its method of preparation and applications thereof |
| WO2001013865A1 (en) * | 1999-08-20 | 2001-03-01 | Howard Murad | Pharmaceutical compositions and methods for reducing the appearance of cellulite |
-
2007
- 2007-02-20 WO PCT/US2007/004549 patent/WO2007100590A2/en active Application Filing
- 2007-02-22 CN CNA2007800098239A patent/CN101405023A/en active Pending
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104603616A (en) * | 2012-09-07 | 2015-05-06 | 株式会社资生堂 | Method of evaluating cellulite and method of evaluating cellulite-effective drug using fibulin-3 and/or sarcoglycan gamma as an indicator |
| CN113015514A (en) * | 2018-09-18 | 2021-06-22 | 恩多全球美学有限公司 | Compositions and methods for treating subcutaneous cellulite |
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| Publication number | Publication date |
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| ZA200807221B (en) | 2009-07-29 |
| WO2007100590A2 (en) | 2007-09-07 |
| WO2007100590A3 (en) | 2008-10-09 |
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