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KR-20260066809-A - COMPOSITIONS AND METHODS FOR TREATING CELLULITE

KR20260066809AKR 20260066809 AKR20260066809 AKR 20260066809AKR-20260066809-A

Abstract

The present disclosure relates to a method for treating cellulite on the thighs or buttocks in human subjects by administering an effective amount of collagenase and evaluating the reduction in cellulite severity by one or more scales.

Inventors

  • 맥레인 마이클
  • 데이비스 매튜 더블유.

Assignees

  • 엔도 글로벌 에스테틱스 리미티드

Dates

Publication Date
20260512
Application Date
20190904
Priority Date
20190711

Claims (20)

  1. As a method to reduce the severity of cellulite on both buttocks of human patients: a. A step of providing a collagenase composition having at least two of the following features: i. V max (min -1 ) of approximately 0.08 to 7.70 (SRC test), or approximately 0.3 to 30.5 (GPA test); ii. K M of about 4.1 to 410 nanomolar (SRC test), or about 0.03 to 3.1 mM (GPA test); iii. K cat (sec -1 ) of approximately 1.1 to 107 (SRC test), or approximately 93 to 9,179 (GPA test); iv. 1/K cat , microsecond of approximately 376 to 37,222 (SRC test), or approximately 4 to 428 (GPA test); v. K cat /K M , mM -1 sec -1 of approx. 5,140 to 508,814 (SRC test), or approx. 60 to 5,934 (GPA test); vi. Molecular mass of about 60 kDa to about 130 kDa, or about 70 to about 130 kDa, or about 80 to about 120 kDa, or about 90 to about 120 kDa, or about 100 to about 110 kDa; vii. At least 80% area purity when measured by reverse-phase HPLC (high-pressure liquid chromatography); viii. Efficacy of about 5,000 to about 30,000 f-SRC units/mg; ix. Efficacy of about 175,000 to about 500,000 f-GPA units/mg; x. Efficacy of about 5,000 to about 25,000 ABC units/mg; xi. Area of impurities selected from the group consisting of Clostridium, Gelatinase, and Leupeptin of 1% or less; xii. Bioburden of 1 cfu/mL or less; and b. Accordingly, the method includes the step of injecting a therapeutically effective amount of the collagenase composition into dimples on both buttocks, wherein the improvement in cellulite appearance is based on the Hexsel Cellulite Severity Scale (Hexsel CSS), Hexsel Depression Depth Scale, Likert Scale, dimple analysis, Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS), Patient Reported Photonumeric Cellulite Severity Scale (PR-PCSS), Investigator Global Aesthetic Improvement Scale (I-GAIS), Subject Global Aesthetic Improvement Scale (S-GAIS), Patient Reported Cellulite Impact Scale (PR-CIS), Abbreviated PR-CIS, and the subject A method established by a scale or other measurement tool selected from a group consisting of the Subject Self-Rating Scale (SSRS), Subject Satisfaction with Cellulite Treatment (SSCT), clinician assessment of cellulite severity (photographs or other images), Body-Q, and validated photometric or other scales used by clinicians and/or patients to assess cellulite severity, improvement, and/or patient satisfaction.
  2. A method according to claim 1, wherein the dimples being treated are not dependent on their size or distance from one another.
  3. A method according to claim 1, wherein the treated dimples are free from skin relaxation, lack of elasticity, or sagging skin.
  4. A method according to claim 1, wherein the patient has multiple treatment visits, and different dimples are treated at different treatment visits.
  5. A method according to claim 1, wherein the injection is performed with a ½ inch needle.
  6. A method according to claim 1, wherein the injection is administered by a clinician who is not dependent on a spacer, ruler, paper, or other device that limits the injection location.
  7. A method according to claim 1, wherein at least one injection is performed at the nadir of the dimple.
  8. A method according to claim 1, wherein multiple injections are performed within 2 cm of each other.
  9. A method according to claim 1, wherein the dimple to be treated is less than 1 cm in length or greater than 2 cm in length.
  10. A method according to claim 1, wherein the patient experiences a rapid response speed to the therapy.
  11. In claim 1, a method wherein, when the treatment is administered to a population of all patients having a moderate or severe CR-PCSS baseline grade, the treatment causes a result selected from the group comprising: a. At least 50% of the above patients show that the severity of CR-PCSS of the buttocks, as assessed in real-time by a clinician, improves by at least one level from baseline on days 22, 43, or 71; b. Indicating that at least 50% of the above patients, while viewing digital images of the buttocks, the severity of PR-PCSS assessed by the subject improved by at least one level from baseline on days 22, 43, or 71; c. At least 5% of the above patients show that the severity of CR-PCSS of the buttocks, as assessed in real-time by a clinician, improves by at least 2 levels from baseline on days 22, 43, or 71; d. Indicating that at least 5% of the above patients, while viewing digital images of the buttocks, the severity of PR-PCSS assessed by the subject improves by at least 2 levels from baseline on days 22, 43, or 71; and e. At least 5% of the above patients experience a reduction in dimple size.
  12. A method according to claim 11, wherein the dimple size reduction parameter is selected from the group consisting of volume, length, width, and depth.
  13. A method according to claim 11, wherein the dimple size reduction is at least 10% reduction on the 22nd, 43rd, or 71st day from the baseline.
  14. A method according to claim 1, wherein the cumulative collagenase dose injected is about 5.04 mg.
  15. Method of claim 1, wherein the collagenase composition comprises AUX-I and AUX-II having the following characteristics: a. AUX-I (SRC Verification): i. V max , min -1 : approx. 0.08 to 7.70 ii. K M : approx. 4.1 to 410 nanomoles iii. K cat , sec -1 : approx. 1.1 to 107 iv. 1/K cat , microsecond: approx. 376 to 37,222 v. K cat /K M , mM -1 sec -1: approx. 5,140 to 508,814 b. AUX-II (GPA Test) i. V max , min -1 : approx. 0.3 to 30.5 ii. K M , mM: approx. 0.03 to 3.1 iii. K cat , sec -1 : approx. 93 to 9,179 iv. 1/K cat , microsecond: approx. 4 to 428 v. K cat /K M , mM -1 sec -1: approx. 60 to 5,934
  16. Method of claim 1, wherein the collagenase composition comprises AUX-I and AUX-II having the following characteristics: a. AUX-I (SRC Verification): i. V max , min -1 : approx. 3.8 ii. K M , mM: approx. 2.07 x 10⁻⁴ iii. K cat , sec -1 : approx. 53 iv. 1/K cat , microsecond: approx. 18,799 v. k cat /K M , mM -1 sec -1: approx. 256,977 b. AUX II (GPA Test): i. V max , min -1 : approx. 15.4 ii. K M , mM: approx. 1.6 iii. K cat , sec -1 : approx. 4,636 iv. 1/K cat , microsecond: approx. 216 v. k cat /K M , mM -1 sec -1: approx. 2,997
  17. A method according to claim 1, wherein the composition comprises at least three of the above features.
  18. A method according to claim 1, wherein the composition comprises at least four of the above features.
  19. A method according to claim 1, wherein the composition comprises at least 5 of the above features.
  20. A method according to claim 1, wherein the composition comprises one or more collagenases of about 1 mg to 20 mg.

Description

Compositions and Methods for Treating Cellulite Related applications The present application claims priority to U.S. provisional application series 62/733,046 filed September 18, 2018; U.S. provisional application series 62/788,916 filed January 6, 2019; U.S. provisional application series 62/812,036 filed February 28, 2019; U.S. provisional application series 62/823,596 filed March 25, 2019; international application series number PCT/US2019/041494 filed July 11, 2019; and international application series number PCT/US2019/41718 filed July 12, 2019, the full text of which is incorporated herein by reference to the maximum extent permitted by law. Technology field The present invention relates to the field of evaluating and treating cellulite. background Cellulite (also known as edematous fibrosclerotic panniculopathy; EFP) is an aesthetic condition that can be understood as an imbalance between structural and biomechanical properties (i.e., delicate sealing and extrusion forces) at the subcutaneous junction (cf. Rudolph et al, "Structural Gender Dimorphism and the Biomechanics of the Gluteal Subcutaneous Tissue: Implications for the Pathophysiology of Cellulite," Plast. Reconstr. Surg . 2019;143(4):1077-1086). Therefore, the goal of cellulite treatment is to reinforce the subcutaneous interface and/or release fibrous septae through various types of subcision (cf. the aforementioned [Rudolph et al.]). Fibrous septa have been recognized as a fundamental cause of cellulite and a target for cellulite treatment through anatomical and imaging analysis studies (cf. Hexsel et al, "Side-by-side comparison of areas with and without cellulite depressions using magnetic resonance imaging," Dermatol Surg. 2009;35(10):1471-1477; Hexsel et al. "Magnetic Resonance Imaging of Cellulite Depressed Lesions Successfully Treated by Subcision," Dermatol Surg. 2016;42(5):693-696; Mirrashed F, Sharp JC, Krause V, Morgan J, Tomanek B. "Pilot study of dermal subcutaneous fat structures by MRI in individuals who differ in gender, BMI, and cellulite grading," Skin Res Technol. 2004;10(3):161-168; Nuernberger and Mueller, "So-called cellulite: an invented disease," J Dermatol Surg Oncol. 1978;4(3):221-229; Pierard et al, "Cellulite: from standing fat herniation to hypodermal stretch marks," Am J Dermatopath. 2000;22(1):34-37; Querleux et al, "Anatomy and physiology of subcutaneous adipose tissue by in vivo magnetic resonance imaging and spectroscopy: relationships with sex and presence of cellulite," Skin Res Technol. 2002;8(2):118-124). To effectively treat cellulite, treatment methods that dissolve or destroy the dermal septa composed of collagen are required (Fig. 1) and cause skin dimpling that is bothersome to many women. While there are therapies used to treat cellulite, there are no approved pharmacological treatments. Despite the various treatment methods, there is little scientific evidence that any of the current non-pharmacological treatments are beneficial. In fact, most of the evidence is based on anecdotal, subjective, or self-assessments by the patients themselves. Some of the past treatments for EFP included weight loss, topical agents, massage, liposuction, mesotherapy, radiofrequency, dermal ablation, motorized dermal ablation, and laser therapy. Many of these treatments exhibit undesirable side effects (cf. Avram MM, "Cellulite: a review of its physiology and treatment," J Cosmet Laser Ther . 2004;6(4):181-185; Collis et al, "Cellulite treatment: a myth or reality: a prospective randomized, controlled trial of two therapies, endermologie and aminophylline cream," Plast Reconstr Surg . 1999;104(4):1110-1114; Khan MH, Victor F, Rao B, Sadick NS. "Treatment of cellulite: Part I. Pathophysiology." J Am Acad Dermatol . 2010;62(3):361-370; Hexsel DM, Mazzuco R. "Subcision: a treatment for cellulite." J Dermatol . 2000;39(7):539-544; Boyce et al, "Clinical evaluation of a device for the treatment of cellulite: Triactive." Am J Cosmet Surg . 2005;22:233-237; DiBernardo BE. "Treatment of cellulite using a 1440-nm pulsed laser with one-year follow-up." Aesthet Surg J . 2011;31(3):328-341). Therefore, many doctors hold the view that improvement in aesthetic condition is not easily achieved. Consequently, there remains an unmet need for safe and effective non-surgical treatments to improve the aesthetic results of women with cellulite. Summary The present invention relates to a method for treating cellulite in human patients by subcutaneously injecting a therapeutically effective amount of collagenase to satisfy the above requirements (as defined in the detailed description). This method relates to a pre-treatment evaluation of the patient's cellulite severity using various scales and evaluation techniques to establish a baseline of the patient's cellulite severity. Then, the cellulite is treated by subcutaneously injecting collagenase. The dosage and administration of collagenase may vary, and the collagenase may be in the form