CA3056919A1 - Method of treatment of skin conditions of eye lids - Google Patents
Method of treatment of skin conditions of eye lids Download PDFInfo
- Publication number
- CA3056919A1 CA3056919A1 CA3056919A CA3056919A CA3056919A1 CA 3056919 A1 CA3056919 A1 CA 3056919A1 CA 3056919 A CA3056919 A CA 3056919A CA 3056919 A CA3056919 A CA 3056919A CA 3056919 A1 CA3056919 A1 CA 3056919A1
- Authority
- CA
- Canada
- Prior art keywords
- skin
- patient
- treatment
- eye lids
- tenting
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 32
- 210000000744 eyelid Anatomy 0.000 title claims abstract description 20
- 238000011282 treatment Methods 0.000 title claims description 23
- 210000003491 skin Anatomy 0.000 claims description 34
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 28
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- 238000002347 injection Methods 0.000 claims description 13
- 239000007924 injection Substances 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 9
- 210000000577 adipose tissue Anatomy 0.000 claims description 6
- 239000001509 sodium citrate Substances 0.000 claims description 6
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 6
- 102000004169 proteins and genes Human genes 0.000 claims description 5
- 108090000623 proteins and genes Proteins 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- 206010015995 Eyelid ptosis Diseases 0.000 claims description 4
- 239000000872 buffer Substances 0.000 claims description 4
- 239000002537 cosmetic Substances 0.000 claims description 4
- 239000003792 electrolyte Substances 0.000 claims description 4
- 201000003004 ptosis Diseases 0.000 claims description 4
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 230000037303 wrinkles Effects 0.000 claims description 3
- 208000002352 blister Diseases 0.000 claims description 2
- 210000002808 connective tissue Anatomy 0.000 claims description 2
- 230000008602 contraction Effects 0.000 claims description 2
- 230000006735 deficit Effects 0.000 claims description 2
- 210000004207 dermis Anatomy 0.000 claims description 2
- 230000001815 facial effect Effects 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 206010033675 panniculitis Diseases 0.000 claims description 2
- 239000011148 porous material Substances 0.000 claims description 2
- 238000005728 strengthening Methods 0.000 claims description 2
- 210000004003 subcutaneous fat Anatomy 0.000 claims description 2
- 238000010254 subcutaneous injection Methods 0.000 claims description 2
- 239000007929 subcutaneous injection Substances 0.000 claims description 2
- 210000004304 subcutaneous tissue Anatomy 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims description 2
- 239000008151 electrolyte solution Substances 0.000 claims 1
- 230000003449 preventive effect Effects 0.000 claims 1
- 201000004569 Blindness Diseases 0.000 description 3
- 230000032683 aging Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 241000299354 Acalles micros Species 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000543381 Cliftonia monophylla Species 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 201000010251 cutis laxa Diseases 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000011283 initial treatment period Methods 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- FFNMBRCFFADNAO-UHFFFAOYSA-N pirenzepine hydrochloride Chemical compound [H+].[H+].[Cl-].[Cl-].C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 FFNMBRCFFADNAO-UHFFFAOYSA-N 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
Classifications
-
- 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
- A61Q19/005—Preparations for sensitive skin
-
- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/345—Alcohols containing more than one hydroxy group
-
- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
-
- 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
- A61K2800/88—Two- or multipart kits
- A61K2800/882—Mixing prior to application
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Dermatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Percussion Or Vibration Massage (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
A method for the hypodermis tightening of fat septa and the reduction of skin tenting, skin lag and skin overhang of the upper and lower eye lids.
Description
2 METHOD OF TREATMENT OF SKIN CONDMONS OF EYE LIDS
STATEMENT AT a: THE RICiTITS TO INVENTIONS MADE UNDER FEDERALLY
SPONSORED RESEARCH AND DEVELOPMENT
[00011 This invention was not made whit government support.
FIELD Of THE:INVENTION
100021 This invention relates to a method of the treatment eye lids with non-surgical blepharopla.sty by injection torevette.Skin tenting and upper eyelid overhang and lower lid laxity.
BACKGROUND
1Ø0031 Overhang:and tenting of the skin in the upper and lower lids of the eyes are uniqUe phenomena that can occur in individuals that are not of an advanced age. The.
Skin in thenpPer: and tower lids of the eyes can be resistant to eye creams for the :reduction ofthe presentation of skin tenting, overhang and Way:: There are no approved or figoronsly evaluated non-surgical alternatives for treatment of these conditions directly at the 'So**, i.e. the. upper and lower lids. Surgical alternatives include various forms Of upper and lower lid blepharopIasties where incisions are made and fat is surgically teased out of candidates. All surgeries, however, are associated with the known risks of anesthesia, infection, bleeding, bruising, scarring, as well as the possibility:Of:Nor outcome and the expected discOnIfOrt and "doWn-time" for the patierit4 :Presently, there are no injections for the upper and lOwer lids that reverse skin tenting, laxitn overhang, sag or puffiness. There has been hesitation in the market to date for injections:into the:
tissue proximal to the orbits:of the eyes. Injections into this anatomical sight Increase the risk of causing blindness in the patient. None of the cosmetic substances currently in the cosmetic:injection market can be injected into the eye lids or the tissue proximal to The orbits of the eyes. There is a need in the market, therefore, for a non-surgical alternative to address *it) conditions of the eye lids which does not pose the risk of causing blindness. õA eitme solution however, could be used to successfully treat skin eonditiOns of thev.YellidS without the risk of causing blindness ill patients. The demand for:non-surgical eye:Corr-000 iS: very highirt:0*vosmetic market.
100041Th spite of procedural risks, the growing appeal of cosmetic medical treatment of said PtoCedUres is a testament to the psychological importance of body image and the benefiCialoutcomes of these procedures, as perceived by the patients who seek them.
However, the significance of a product that corrects signs of pen-orbital aging with little to no risk is significant.
BRIEF DESCRIPTION OF THE INVENTION
106051 The present in$41tWt:is directed to a method for the non-surgical reduction of Localized loose skin in the upper and. lower lids that is associated with the normal aging loss of the integrity of the derthiS-that supports the epidermis. The upper lid tenting and overhang and 16*g:11d:tenting, overhang and laxity can give the appearance of one looking tired when not in particular, a treatment for skin tenting, lid laxity, sag and overhang in the upper and lower lids Ofthe eyes with an aqueous solution of citric acid with a viscosity consistent with water at 26 to 25 C.
D.MAIUD DM:Rip-TM OF THE INVENTION
100061 The Invention provides a method fOr improvement of the tired look of human skin of the eye lids cOmprising administering citric acid or a salt thereof to a patient in need thereof; wherein the administering is a submitaneouS injection. The method tightens subcutaneous fat via strengthening of wall proteins:located in the hypodemils of the skin of the upper and IoWer eye lids to thereby enhance facial appearance. The injection is, for example, in the form of one or more large blebs or small boluses. The method may also include an additional step of measuring one or more improvements in the appearance of the skin with a measuring device. When the citric acid:or salt thereof is placed in the superficial plane or deep plains of sulxlermal fat, it causes skin tightening by connective tissue contractions, increase support of the subcutaneous tissue, and tensile strength to protein strands below the derinis. 'The citric acid or salt thereof may he either natural or betic 100071 The cOnlpositions, treatment schedules and methods of using said compositions discovered by the inventor effectively remove the effect of tenting or impending tenting of the upper and lower lids.. Generally speaking, tenting and impending tenting and tented skin ptosis of the upper and lower:lids of the eyes are a well-known beauty problems; problems that can progress to visual impairment if treatment to reverse the presentation of the tented and hanging skin is delayed. In addition, the effect of tightening tented and hanging skin with .subcutaneous injections repositions fat and re-compartmentaliz.es fatty tissue in its more anatOinically correct position.
[00081 Citrate constituted with isotonic water and dextrose can stimulate elastin tensile strength below the dermis and above and below the muscle to tighten skin, decrease the appearance of aging, and contour deficiencies, fine lines and wrinkles.
Citrate is found in the serum of individuals. but also can be manufactured and processed, [00091 The composition of the instant application is based on 100 volume percent calculations. In:particular, the composition of the instant application is comprised of:
volume percent: 3.2 % sodiumeitrate buffer. In the preferred embodiment, aPPr*irt1401Y-10911.410r$Odiurncitrate buffer is used. Citric acid, having the loin-mill.
CH2C00}1 tiOCC0014 etntobli,: May also be nsed.
The 11 4:sodium citrate :buffer or citric acid is combined together with 90 volume permit: :364 %isotonic miter, 45% sodium chloride and 6.4% glycerol with.
trace electrolytes.
[00101 The invention also encompasses a kit. The kit includes the following items 1), sodium citrate powder. or a solution thereof, pre-loaded into a 20 cc intravenous vial for.
dispensing, 2). an 8 10 10 (*.Syringe of a liquid volume comprising isotonic water,
STATEMENT AT a: THE RICiTITS TO INVENTIONS MADE UNDER FEDERALLY
SPONSORED RESEARCH AND DEVELOPMENT
[00011 This invention was not made whit government support.
FIELD Of THE:INVENTION
100021 This invention relates to a method of the treatment eye lids with non-surgical blepharopla.sty by injection torevette.Skin tenting and upper eyelid overhang and lower lid laxity.
BACKGROUND
1Ø0031 Overhang:and tenting of the skin in the upper and lower lids of the eyes are uniqUe phenomena that can occur in individuals that are not of an advanced age. The.
Skin in thenpPer: and tower lids of the eyes can be resistant to eye creams for the :reduction ofthe presentation of skin tenting, overhang and Way:: There are no approved or figoronsly evaluated non-surgical alternatives for treatment of these conditions directly at the 'So**, i.e. the. upper and lower lids. Surgical alternatives include various forms Of upper and lower lid blepharopIasties where incisions are made and fat is surgically teased out of candidates. All surgeries, however, are associated with the known risks of anesthesia, infection, bleeding, bruising, scarring, as well as the possibility:Of:Nor outcome and the expected discOnIfOrt and "doWn-time" for the patierit4 :Presently, there are no injections for the upper and lOwer lids that reverse skin tenting, laxitn overhang, sag or puffiness. There has been hesitation in the market to date for injections:into the:
tissue proximal to the orbits:of the eyes. Injections into this anatomical sight Increase the risk of causing blindness in the patient. None of the cosmetic substances currently in the cosmetic:injection market can be injected into the eye lids or the tissue proximal to The orbits of the eyes. There is a need in the market, therefore, for a non-surgical alternative to address *it) conditions of the eye lids which does not pose the risk of causing blindness. õA eitme solution however, could be used to successfully treat skin eonditiOns of thev.YellidS without the risk of causing blindness ill patients. The demand for:non-surgical eye:Corr-000 iS: very highirt:0*vosmetic market.
100041Th spite of procedural risks, the growing appeal of cosmetic medical treatment of said PtoCedUres is a testament to the psychological importance of body image and the benefiCialoutcomes of these procedures, as perceived by the patients who seek them.
However, the significance of a product that corrects signs of pen-orbital aging with little to no risk is significant.
BRIEF DESCRIPTION OF THE INVENTION
106051 The present in$41tWt:is directed to a method for the non-surgical reduction of Localized loose skin in the upper and. lower lids that is associated with the normal aging loss of the integrity of the derthiS-that supports the epidermis. The upper lid tenting and overhang and 16*g:11d:tenting, overhang and laxity can give the appearance of one looking tired when not in particular, a treatment for skin tenting, lid laxity, sag and overhang in the upper and lower lids Ofthe eyes with an aqueous solution of citric acid with a viscosity consistent with water at 26 to 25 C.
D.MAIUD DM:Rip-TM OF THE INVENTION
100061 The Invention provides a method fOr improvement of the tired look of human skin of the eye lids cOmprising administering citric acid or a salt thereof to a patient in need thereof; wherein the administering is a submitaneouS injection. The method tightens subcutaneous fat via strengthening of wall proteins:located in the hypodemils of the skin of the upper and IoWer eye lids to thereby enhance facial appearance. The injection is, for example, in the form of one or more large blebs or small boluses. The method may also include an additional step of measuring one or more improvements in the appearance of the skin with a measuring device. When the citric acid:or salt thereof is placed in the superficial plane or deep plains of sulxlermal fat, it causes skin tightening by connective tissue contractions, increase support of the subcutaneous tissue, and tensile strength to protein strands below the derinis. 'The citric acid or salt thereof may he either natural or betic 100071 The cOnlpositions, treatment schedules and methods of using said compositions discovered by the inventor effectively remove the effect of tenting or impending tenting of the upper and lower lids.. Generally speaking, tenting and impending tenting and tented skin ptosis of the upper and lower:lids of the eyes are a well-known beauty problems; problems that can progress to visual impairment if treatment to reverse the presentation of the tented and hanging skin is delayed. In addition, the effect of tightening tented and hanging skin with .subcutaneous injections repositions fat and re-compartmentaliz.es fatty tissue in its more anatOinically correct position.
[00081 Citrate constituted with isotonic water and dextrose can stimulate elastin tensile strength below the dermis and above and below the muscle to tighten skin, decrease the appearance of aging, and contour deficiencies, fine lines and wrinkles.
Citrate is found in the serum of individuals. but also can be manufactured and processed, [00091 The composition of the instant application is based on 100 volume percent calculations. In:particular, the composition of the instant application is comprised of:
volume percent: 3.2 % sodiumeitrate buffer. In the preferred embodiment, aPPr*irt1401Y-10911.410r$Odiurncitrate buffer is used. Citric acid, having the loin-mill.
CH2C00}1 tiOCC0014 etntobli,: May also be nsed.
The 11 4:sodium citrate :buffer or citric acid is combined together with 90 volume permit: :364 %isotonic miter, 45% sodium chloride and 6.4% glycerol with.
trace electrolytes.
[00101 The invention also encompasses a kit. The kit includes the following items 1), sodium citrate powder. or a solution thereof, pre-loaded into a 20 cc intravenous vial for.
dispensing, 2). an 8 10 10 (*.Syringe of a liquid volume comprising isotonic water,
-3-sodium chloride, glycerol and trace electrolytes; and an injector device to reconstitute'the dry elements. The injector, mixes the Ingredients back and forth hetvveen two 10 cc syringes until the formula is reconstituted to a dose of I Oml prior to administration.
100111 The mixture should have a neutral pH priorloinjection. In addition, the prepared solution should exhibit the viscosity of water at 20.to 2C at the tiineof injection.
OM The cOrtiPOsition attic instant application tor the subcutaneous reversal of skin 'tenting; snjag:of the upper andlor lower lid shot 14 be administered only by competent plastiesttrgeons, dermatologists or other medical doctors and their eligible licensed staff.
Injections into the sub-dermal fat tissue in patients having skin tenting, sag or lag of the eye lids wilt tighten and thicken the subdermal fat bands and the hypodermis thereby reducing the appearance of fine lines, wrinkles, and pores of the eye lids.
190131 Formulations suitable for administration, conveniently comprise sterile aqueous solutions of the active ingredient(s). Preparations may be sterilized by, fOr example, filtration through a bacteria-retaining filter, by incorporating sterilizing agents into the compositions, by irradiating the compositions, or by heating the compositions.
Preparations can also be manufactured in the form' of sterile solid compositions which can be dissolved in sterile water or some other sterile injectable medium immediately before use. The formulation may be presented in Wit or multi-dose containers.
for example, sealed ampoules or vials, PcAMPUS
100141 Prior to treatment, phOtographs are taken Of the: patients= eyelids. An initial treatment period involves up to 2 to 3 treatments involving an initial treatment with usually two subsequent follow-up treatments, i.e. a follow-up treatment and a follow-up to the follow-up treatment. When the appearance of the correction of the subcutaneous wall protein deficit of the upper and tower lids is observed, treatment is usually halted.
At the initiall treatment session, the consulthnt discusses the intended goals with the patient and then determines ifthe patient is a candidate for the follow-up to the follow-pp treatment. The provider determines the appropriate number of milliliters of citric
100111 The mixture should have a neutral pH priorloinjection. In addition, the prepared solution should exhibit the viscosity of water at 20.to 2C at the tiineof injection.
OM The cOrtiPOsition attic instant application tor the subcutaneous reversal of skin 'tenting; snjag:of the upper andlor lower lid shot 14 be administered only by competent plastiesttrgeons, dermatologists or other medical doctors and their eligible licensed staff.
Injections into the sub-dermal fat tissue in patients having skin tenting, sag or lag of the eye lids wilt tighten and thicken the subdermal fat bands and the hypodermis thereby reducing the appearance of fine lines, wrinkles, and pores of the eye lids.
190131 Formulations suitable for administration, conveniently comprise sterile aqueous solutions of the active ingredient(s). Preparations may be sterilized by, fOr example, filtration through a bacteria-retaining filter, by incorporating sterilizing agents into the compositions, by irradiating the compositions, or by heating the compositions.
Preparations can also be manufactured in the form' of sterile solid compositions which can be dissolved in sterile water or some other sterile injectable medium immediately before use. The formulation may be presented in Wit or multi-dose containers.
for example, sealed ampoules or vials, PcAMPUS
100141 Prior to treatment, phOtographs are taken Of the: patients= eyelids. An initial treatment period involves up to 2 to 3 treatments involving an initial treatment with usually two subsequent follow-up treatments, i.e. a follow-up treatment and a follow-up to the follow-up treatment. When the appearance of the correction of the subcutaneous wall protein deficit of the upper and tower lids is observed, treatment is usually halted.
At the initiall treatment session, the consulthnt discusses the intended goals with the patient and then determines ifthe patient is a candidate for the follow-up to the follow-pp treatment. The provider determines the appropriate number of milliliters of citric
-4-solution tabe.injeeted into the defective spaces of the subdermal fat planes.
on average a.
range of 2 nits to 1.2 nils of citric add solution is. employed, During treatment, a hypodermic need is used to inject the citric acid with sterile water as an aqueous mixture . .
in.a.micro droplet and .microlluidie pattern into the defective space in the orbital lids targeting the preapOneurotic.fatpads, medial fat pads, temporal fat pads, medial fat pads =
as =ell'as the fattYcell'ilayers. The solution Immediately reabsorbs into sitbdennal planes. Residual swellingWill be appreciated for 24 hours followed by reabsorption of the solution. The initial, local inflammatory response heals at a.varying rate depending On the individual patient with the majority of pati.ent.s.-ItcalingtOmpletely within two weeks or less. 'Results from the treatment can be appreciated in 4 to 6 weeks With maximum results in 12 months and beyond. Blood test can he used to monitor the dermal response to thetreattrient. Before and after photography is used to consult with the recipient in one month, three months; 12 months as recommended visits and a 24-month visit with.photography is optional.
100151 Example 1...:.
=.:=:=õ:-:-.i:i:i:.i,-,.i.:.::::...:.::.,.....,.i,ii:...i:i:i:ii:i:i:===:i...::::.::::::g:::::::ii:::
:.:::::::ii:::,:,i,:i,i,:,:,i,i:,:,:,:,:,:,i,,::::ii.::.::.:i;:;:;:;:::::::::::
i:::::i:::i:ii...,:::=:.,:.:,:mmeims,:i;i,i.=::0,:,i,:,,I,1,,,1õõõõ,g,,,,,,,,,, õõõõ,,,,,,,,,,.,.,.,.,.,.,..,.,.,.,.,...,,,,,,.,.,....,,.:..,.,.,.,.,..........
.....,.,............
:::."''':."'""'"""'"'"""""':::""''""'.:"""''""'"""',',',',',',','""""","i':'i'i ,,i,i,,,i,i,i,i,i,i,:ii:=::=::=::=:'i'i'':::=::=ii:::*::=ii::=!:=::=::=:
:i:aii:.:;tiiiiiiiitiiiiiiiiiiiiiiiitiitiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii iiini??:iiini ,ig.,i.,i.,i.õ.õ.õ.õ.õ.:,i,i=::,i=:.õ.õ,õ,õ,,=,::=:.,=,:,=,:,=:.:,=,:,=,=:;;;,, ,:,,',i,:!..,i,=:.;;;;;;,:...;;.!..gi . . = = .... ---- -====== = ============ = = ..-:::=:. :
Upper lid tightening.
. . .
============............=================-===================================-=-====
. .. ..... .
....x..........x.:.:.õ.....:õ....:....:....,.:,.:.......:.:....................
.........................................
= : : :,-.....::
:,......,........:::=:::::::=.......:.i.,- . :-.. ,..,...,.. , _.õ. = = =.,=.,=====,=, =======
==============x::::::.:::=........::::::::::,............::::.:=..........,...:
::.,.........:.,...:.,.,......,......:,....,,.,.:.=,.:.,:.......:..,.::::::..
===:==,,Y:..z,,.....04','$..v '.... ..,, . ,..'..; ....-..,=====......,..,=.:=.....=::, .. = .. :.:......., . T::,z...,=i.,,,'.,-w,.'N,r7,...=.===..-..:...=
iiiiKkgm........ignesz,...,..z...,..,...:.:.::.:......
.........1..:.:...,..,:.....,z,..,,A.,...,....--.:,...,,.,...,.v....-:..-::::
= .- .==== : = '=.=,...k\=, ,....., - ':,:.': -,-,....:=:".:- ==:
::...::::..........,:...:Ø,..,=.......m.........,.....,.....::,....::::::::::
:....::=:im:....::=,....., :
cl4'..'',''.<,-.-;:-. ...:*õ.= : õ,,'. '. ...,-.-',;..Z,:'-i.... =:==
' . . -. '= =: V ,- , ,õ-::: = ' ,,,,-. -õõ:-. . -_'-.-,.:',-..:=,, '' :::i::::::::::::::::::0:::ii:::0::::..........-::-..........:=::::-.1:::-...:,.........:-.......:::::::::::Iii:::::: ..
''''.:':=======:.='''''. N'' ''N''''''''.'''.= = = ' ' k'''' \ \
'W'''..''''''*, ,-,...:=''."',.-;.-','.:=.` ' ,' '..r-r=-': .M.i=-::::::0-::::::::::::....:::::::::Z...;....-:-..,.::::I=.:::-.:,.::,u=-.=:=:==
.
,,õ....,=.:.-,:=-....,,=::%;I:''7-.7.;:*...-:::ii..?.....i '-: . ' :
''t''' --:';-.:.. ,-.:=i"z'''- '.----::--'= ' . :. =-='-':'l :::.:::.:::.;i;i;:::::::::ffi;;":;::::-...;,MW:::'-':'.':N.::1::',.=:'..:;.:',1:::','::=::=.=.::.
.õ'. =...., 4-f=-.1.1::::',21...,I ,....:.::: .: ..
= .= \ = - `,::i......,:''.1..1.', 't,,' *,,,,:k "' = ._ _ 'll';':" :.:
iiiiiii:iiiiii.:i.in.i.:::.,::::::ni.gini.ii:".:NN:.:!':Ni::::
... 4.=-=,:-....',..',==.,.....:',..=---:: I's =,.== : :, ,' ===== ',,,,. = = : \ ''.::=,...:.,:-.:=:..:.,-.i=-=''.=:.,=:,1 ''...,7111MAggiMen,..r.1...":fi... =
\ .....:a''',:..-:õH'...- :====,..-'.. kVk.':: \=*, \\\\
',',', ' ' , :== .. '' = .s...,.%......:.=,.-Y-,;,,-*\\\ µ
,"R...fil..:*:.:f6',.:.:,:.::.:::::::-.,.:::::-..i::::.:::.i=-...-:-.i.:.i:.iii-k:::-?..:,.ii:::::::
,.''=\\...õ=\*,:.:i.:',,fi-=.K,...õ,.`,,,'N'S\ : > \'' ...::, ..::::'''''':,=,= ....:: .::-.'''.:.*:',,N..-=.N1,..'s \`=\ µ= :'`'''' ..'*: =:.:.
===<;:xs======='-'k.:-.,',,=::::',,:-N = \ =='=-==========õ\ ' :
:=,=:= \Nõ . ..\.= =-= , ====:., -:.-, .. = ===.-,k,\
;::':::.*:.:.;:',':=1.:-.:1.=:::.:.::.=:..:;...-A;;;:.:::::U.:e.-...,:1:.:U,:,=,:.
'''\V`',".<-..,',:;..,1-,-====='''..-:=:..,,.......---,,.., .: \N\N'. '',-:- =
= ' ' ::. ,,,,,s..'s-''' ' ' ==-'-'N .*M:M:i.iin::::::6;;;::-.;;;;;:.;;Min:;;ANiKK
;:. ::...,-=\\\ 'µ`I'*-=:1.......;',... :: s' \'' '''''''k-N:::
====::::::: .".. = ' :: N'-'::' . - = .µ..=*k `.--Z
Mang.iii:::::::::::::Bi:!::.M.MiniVi!.'i.:-.M
\
\\
: :' ::....:: '-µk' .:-...i.L,...,,H:k1'.'s'4µkkõ\\''N \''!:_k..: :::::!: ====::.:' .:: .. :
,....'.1::,,,.=...''''''-':',.$.-....'::='S.i;.1::i:iiiM::::iiiii!iiiiMigiBiggi;;I.:i.l.:11;:::igi'.:lin ' -=`` '..'s,>''''''''.- s . ..... = *.s. ...\\....'ss'=: . '' -'''' , = ^ = x:'.`., '..,..,.:..,::::::::::::.::::::.:::::::::.:::::::::::::.:::::::::::i*r...:::::*
::::i::::::::::.*::.:0:::,.........::
: : = : -.: ...1 \ .',;:agits,.-õ,...,:::'..,õsl.N., -1< :::::::........::::::::........:.:.:?:iiii. \
''\=:::::?...4,,.. ...&-.;...'.<4*...:M......:M:.i:::::::::::::::NE....g..::::::ig:::::::::::::::::::::
...;.......
. --: .::::..:k2., \,` =-N'.. \ \
...............:........,i,ii,i,i,.......
\
. :: : . .:::H.'N ,.. ,-*'..*=
\''....,.E....g..j.i.:===ii,-=::.,:=:L = ' \>. = \ \ =
4::::,...':.,...:Ma....:=:E...:..........::::::::::.:::i.:',,....,..;,.::.a::=:
:,::::'=;,==,.==:==:::
. . .
= = = =
- -"'........:::::=i'===::============:;'...........:::::::::::=======*=========:, ..;,*i.....*::====:,::::::::=::::=:,i'=*::::=*i,=,;,:iiiiii*=,.,....::::.*=,:.=
=,==,=,....:::==============,i,i:::::::::i*.:*.::::.:g::*i::.:::::::::,.:,..:ii :?..,.::::.:::::,.,:::::::::.,,,....:.:0::=:::::::.::::. : :
. . ':, " = = = = ===:.
==::::.=:=====,....,.'=====,;:::::::::::::: .. : : . =======.::
:?.: = : : :
=:..::::::::::.:::.:::i=:i=.==..=:=:=:iii..:=:i=:iiii.w=:iiiii:.iii:.iiiii:iiii iiiiiii:.i'=.iiiiiiiiii:i:i:i:=,i:i:i:i:i:i:i:i:=::i:i:i:i:i:i::::,::::::::::::
::::::,::x::*i:i::*::..,.:..:::..,.=,:=:==.=?=i:::K::*=.,.,.,.,=:...::=:,..::,.
*.::,.:==.:=,=,,,,,:::..:.=
. ... ... = " " " " " " " "
"===================================:=:=:=:=,=:=:=:=:=:=:=:=:=:=:=:=:=:=:::::,, ,,,,,,,,,,,,,,,,,,.::.:.:.:.:.:.:....:.:.:,,,,..:,,,....:.:..............,.....
.....................õ....,.... = = ===== = == ==== === = == == ==
= = =============== =-================ ......===========
................................................................
..............................
= = = = = ==== .
========= . . . . . . = = = = = .....................
...............................................................................
............................................................ - - ......=
= . =
== == ============= ===
================= == ========== = ====================........==========
...............................................................................
..................
.= == .= = . =
=.... :....= ......,======,========================== ======,..,.=
......................=====:.
....===========..............:===========..................,...................
.....,===............,,.,.,.,;;;;;:.:.:.:.:.:.:.:.:.:.:.:::::::::::............
..............................:::::::::::::::::::::.:.:.:.:.:.........:::::....
...................................:.:.:.::.:.õ........õ..................õ....
.............................................................. : .........
. .. ... .. ==== = ==== ==== === = = ==== . ..... -"============= = = = = = = = = . = = = = = = = = = = =
...."===============.........................============......................
...............................................................................
...................................:...........................................
....
== = = = = = = = = = . = = == = =============== = . = = = - .
........ -.......=-=========================================........======================= = = =
= = = = = = = ==== = = = = = = = = = = = = = = = = = = = = = = = = = = =
= = = = ..........= = = = = = = = = = ....................... ......... ...
. . = . . = = = = ........................ .... ............
...... .. ............. . .............. = = . " = = = = = . = .
= = = = ..., = . = . = . = . = . = . = . = . = . = . = . = . . . : . : . : = =
..= . = " . = . = . = . = = . = " = . = . = . = . = . = . = . = = . : . . . :
" : . : . = . : . : . : . : . : . = . = . = . = . = . : = .: = ..= = i = ... =
... = : : = : = = = = = = = = = = = = = = = = = = :. = ... = :==.= :==.= .., =,=:. : = : = : = : = : = : = : :. . :. . :. . i . == : . : . : . = . .= . : .
: . :. . : ..: . : . . . . . .. .. . : . : . : . = . = . = . = . = . = . = . =
. = = . .. . : . " = . = . = . = = = , : : .. .. .. .. .. : : : = = = = = = =
= = = = .= .= .= .= : : .= .= = = = = = = = . = . = = = . . - . . . . .
. . .....
on average a.
range of 2 nits to 1.2 nils of citric add solution is. employed, During treatment, a hypodermic need is used to inject the citric acid with sterile water as an aqueous mixture . .
in.a.micro droplet and .microlluidie pattern into the defective space in the orbital lids targeting the preapOneurotic.fatpads, medial fat pads, temporal fat pads, medial fat pads =
as =ell'as the fattYcell'ilayers. The solution Immediately reabsorbs into sitbdennal planes. Residual swellingWill be appreciated for 24 hours followed by reabsorption of the solution. The initial, local inflammatory response heals at a.varying rate depending On the individual patient with the majority of pati.ent.s.-ItcalingtOmpletely within two weeks or less. 'Results from the treatment can be appreciated in 4 to 6 weeks With maximum results in 12 months and beyond. Blood test can he used to monitor the dermal response to thetreattrient. Before and after photography is used to consult with the recipient in one month, three months; 12 months as recommended visits and a 24-month visit with.photography is optional.
100151 Example 1...:.
=.:=:=õ:-:-.i:i:i:.i,-,.i.:.::::...:.::.,.....,.i,ii:...i:i:i:ii:i:i:===:i...::::.::::::g:::::::ii:::
:.:::::::ii:::,:,i,:i,i,:,:,i,i:,:,:,:,:,:,i,,::::ii.::.::.:i;:;:;:;:::::::::::
i:::::i:::i:ii...,:::=:.,:.:,:mmeims,:i;i,i.=::0,:,i,:,,I,1,,,1õõõõ,g,,,,,,,,,, õõõõ,,,,,,,,,,.,.,.,.,.,.,..,.,.,.,.,...,,,,,,.,.,....,,.:..,.,.,.,.,..........
.....,.,............
:::."''':."'""'"""'"'"""""':::""''""'.:"""''""'"""',',',',',',','""""","i':'i'i ,,i,i,,,i,i,i,i,i,i,:ii:=::=::=::=:'i'i'':::=::=ii:::*::=ii::=!:=::=::=:
:i:aii:.:;tiiiiiiiitiiiiiiiiiiiiiiiitiitiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiii iiini??:iiini ,ig.,i.,i.,i.õ.õ.õ.õ.õ.:,i,i=::,i=:.õ.õ,õ,õ,,=,::=:.,=,:,=,:,=:.:,=,:,=,=:;;;,, ,:,,',i,:!..,i,=:.;;;;;;,:...;;.!..gi . . = = .... ---- -====== = ============ = = ..-:::=:. :
Upper lid tightening.
. . .
============............=================-===================================-=-====
. .. ..... .
....x..........x.:.:.õ.....:õ....:....:....,.:,.:.......:.:....................
.........................................
= : : :,-.....::
:,......,........:::=:::::::=.......:.i.,- . :-.. ,..,...,.. , _.õ. = = =.,=.,=====,=, =======
==============x::::::.:::=........::::::::::,............::::.:=..........,...:
::.,.........:.,...:.,.,......,......:,....,,.,.:.=,.:.,:.......:..,.::::::..
===:==,,Y:..z,,.....04','$..v '.... ..,, . ,..'..; ....-..,=====......,..,=.:=.....=::, .. = .. :.:......., . T::,z...,=i.,,,'.,-w,.'N,r7,...=.===..-..:...=
iiiiKkgm........ignesz,...,..z...,..,...:.:.::.:......
.........1..:.:...,..,:.....,z,..,,A.,...,....--.:,...,,.,...,.v....-:..-::::
= .- .==== : = '=.=,...k\=, ,....., - ':,:.': -,-,....:=:".:- ==:
::...::::..........,:...:Ø,..,=.......m.........,.....,.....::,....::::::::::
:....::=:im:....::=,....., :
cl4'..'',''.<,-.-;:-. ...:*õ.= : õ,,'. '. ...,-.-',;..Z,:'-i.... =:==
' . . -. '= =: V ,- , ,õ-::: = ' ,,,,-. -õõ:-. . -_'-.-,.:',-..:=,, '' :::i::::::::::::::::::0:::ii:::0::::..........-::-..........:=::::-.1:::-...:,.........:-.......:::::::::::Iii:::::: ..
''''.:':=======:.='''''. N'' ''N''''''''.'''.= = = ' ' k'''' \ \
'W'''..''''''*, ,-,...:=''."',.-;.-','.:=.` ' ,' '..r-r=-': .M.i=-::::::0-::::::::::::....:::::::::Z...;....-:-..,.::::I=.:::-.:,.::,u=-.=:=:==
.
,,õ....,=.:.-,:=-....,,=::%;I:''7-.7.;:*...-:::ii..?.....i '-: . ' :
''t''' --:';-.:.. ,-.:=i"z'''- '.----::--'= ' . :. =-='-':'l :::.:::.:::.;i;i;:::::::::ffi;;":;::::-...;,MW:::'-':'.':N.::1::',.=:'..:;.:',1:::','::=::=.=.::.
.õ'. =...., 4-f=-.1.1::::',21...,I ,....:.::: .: ..
= .= \ = - `,::i......,:''.1..1.', 't,,' *,,,,:k "' = ._ _ 'll';':" :.:
iiiiiii:iiiiii.:i.in.i.:::.,::::::ni.gini.ii:".:NN:.:!':Ni::::
... 4.=-=,:-....',..',==.,.....:',..=---:: I's =,.== : :, ,' ===== ',,,,. = = : \ ''.::=,...:.,:-.:=:..:.,-.i=-=''.=:.,=:,1 ''...,7111MAggiMen,..r.1...":fi... =
\ .....:a''',:..-:õH'...- :====,..-'.. kVk.':: \=*, \\\\
',',', ' ' , :== .. '' = .s...,.%......:.=,.-Y-,;,,-*\\\ µ
,"R...fil..:*:.:f6',.:.:,:.::.:::::::-.,.:::::-..i::::.:::.i=-...-:-.i.:.i:.iii-k:::-?..:,.ii:::::::
,.''=\\...õ=\*,:.:i.:',,fi-=.K,...õ,.`,,,'N'S\ : > \'' ...::, ..::::'''''':,=,= ....:: .::-.'''.:.*:',,N..-=.N1,..'s \`=\ µ= :'`'''' ..'*: =:.:.
===<;:xs======='-'k.:-.,',,=::::',,:-N = \ =='=-==========õ\ ' :
:=,=:= \Nõ . ..\.= =-= , ====:., -:.-, .. = ===.-,k,\
;::':::.*:.:.;:',':=1.:-.:1.=:::.:.::.=:..:;...-A;;;:.:::::U.:e.-...,:1:.:U,:,=,:.
'''\V`',".<-..,',:;..,1-,-====='''..-:=:..,,.......---,,.., .: \N\N'. '',-:- =
= ' ' ::. ,,,,,s..'s-''' ' ' ==-'-'N .*M:M:i.iin::::::6;;;::-.;;;;;:.;;Min:;;ANiKK
;:. ::...,-=\\\ 'µ`I'*-=:1.......;',... :: s' \'' '''''''k-N:::
====::::::: .".. = ' :: N'-'::' . - = .µ..=*k `.--Z
Mang.iii:::::::::::::Bi:!::.M.MiniVi!.'i.:-.M
\
\\
: :' ::....:: '-µk' .:-...i.L,...,,H:k1'.'s'4µkkõ\\''N \''!:_k..: :::::!: ====::.:' .:: .. :
,....'.1::,,,.=...''''''-':',.$.-....'::='S.i;.1::i:iiiM::::iiiii!iiiiMigiBiggi;;I.:i.l.:11;:::igi'.:lin ' -=`` '..'s,>''''''''.- s . ..... = *.s. ...\\....'ss'=: . '' -'''' , = ^ = x:'.`., '..,..,.:..,::::::::::::.::::::.:::::::::.:::::::::::::.:::::::::::i*r...:::::*
::::i::::::::::.*::.:0:::,.........::
: : = : -.: ...1 \ .',;:agits,.-õ,...,:::'..,õsl.N., -1< :::::::........::::::::........:.:.:?:iiii. \
''\=:::::?...4,,.. ...&-.;...'.<4*...:M......:M:.i:::::::::::::::NE....g..::::::ig:::::::::::::::::::::
...;.......
. --: .::::..:k2., \,` =-N'.. \ \
...............:........,i,ii,i,i,.......
\
. :: : . .:::H.'N ,.. ,-*'..*=
\''....,.E....g..j.i.:===ii,-=::.,:=:L = ' \>. = \ \ =
4::::,...':.,...:Ma....:=:E...:..........::::::::::.:::i.:',,....,..;,.::.a::=:
:,::::'=;,==,.==:==:::
. . .
= = = =
- -"'........:::::=i'===::============:;'...........:::::::::::=======*=========:, ..;,*i.....*::====:,::::::::=::::=:,i'=*::::=*i,=,;,:iiiiii*=,.,....::::.*=,:.=
=,==,=,....:::==============,i,i:::::::::i*.:*.::::.:g::*i::.:::::::::,.:,..:ii :?..,.::::.:::::,.,:::::::::.,,,....:.:0::=:::::::.::::. : :
. . ':, " = = = = ===:.
==::::.=:=====,....,.'=====,;:::::::::::::: .. : : . =======.::
:?.: = : : :
=:..::::::::::.:::.:::i=:i=.==..=:=:=:iii..:=:i=:iiii.w=:iiiii:.iii:.iiiii:iiii iiiiiii:.i'=.iiiiiiiiii:i:i:i:=,i:i:i:i:i:i:i:i:=::i:i:i:i:i:i::::,::::::::::::
::::::,::x::*i:i::*::..,.:..:::..,.=,:=:==.=?=i:::K::*=.,.,.,.,=:...::=:,..::,.
*.::,.:==.:=,=,,,,,:::..:.=
. ... ... = " " " " " " " "
"===================================:=:=:=:=,=:=:=:=:=:=:=:=:=:=:=:=:=:=:::::,, ,,,,,,,,,,,,,,,,,,.::.:.:.:.:.:.:....:.:.:,,,,..:,,,....:.:..............,.....
.....................õ....,.... = = ===== = == ==== === = == == ==
= = =============== =-================ ......===========
................................................................
..............................
= = = = = ==== .
========= . . . . . . = = = = = .....................
...............................................................................
............................................................ - - ......=
= . =
== == ============= ===
================= == ========== = ====================........==========
...............................................................................
..................
.= == .= = . =
=.... :....= ......,======,========================== ======,..,.=
......................=====:.
....===========..............:===========..................,...................
.....,===............,,.,.,.,;;;;;:.:.:.:.:.:.:.:.:.:.:.:::::::::::............
..............................:::::::::::::::::::::.:.:.:.:.:.........:::::....
...................................:.:.:.::.:.õ........õ..................õ....
.............................................................. : .........
. .. ... .. ==== = ==== ==== === = = ==== . ..... -"============= = = = = = = = = . = = = = = = = = = = =
...."===============.........................============......................
...............................................................................
...................................:...........................................
....
== = = = = = = = = = . = = == = =============== = . = = = - .
........ -.......=-=========================================........======================= = = =
= = = = = = = ==== = = = = = = = = = = = = = = = = = = = = = = = = = = =
= = = = ..........= = = = = = = = = = ....................... ......... ...
. . = . . = = = = ........................ .... ............
...... .. ............. . .............. = = . " = = = = = . = .
= = = = ..., = . = . = . = . = . = . = . = . = . = . = . = . . . : . : . : = =
..= . = " . = . = . = . = = . = " = . = . = . = . = . = . = . = = . : . . . :
" : . : . = . : . : . : . : . : . = . = . = . = . = . : = .: = ..= = i = ... =
... = : : = : = = = = = = = = = = = = = = = = = = :. = ... = :==.= :==.= .., =,=:. : = : = : = : = : = : = : :. . :. . :. . i . == : . : . : . = . .= . : .
: . :. . : ..: . : . . . . . .. .. . : . : . : . = . = . = . = . = . = . = . =
. = = . .. . : . " = . = . = . = = = , : : .. .. .. .. .. : : : = = = = = = =
= = = = .= .= .= .= : : .= .= = = = = = = = . = . = = = . . - . . . . .
. . .....
- 5-f041161 Pitai11.ple=:::Z.::
... .......,................., ..........i:::i..,õõ.. ...::::::õ..:õ.. :.,õ: ====== - ....::õ,, ,,,,,, :"":: ...,. ...m...õ:.::::::g ::::::.:1::,i:.::--:::::m:::.:.:..i::i....:.::::?.?:::::0:iimiikk.:::::%::Roii;.1:,:=.::::::ii:i::
..igt.:ii::;":..::::::::it.:-:.::,:,:.,::::::,...:0 Upper h0. tIghtenf ng: , , :.,.,.. ....,,..
,.i.,,,..õ.,:,:.::,....z.7.,.....õ,...,:.....:,:,:?:.:...............õ, ,....... ....õ:õ... t.. . ... .. .... t..... . ... . . : .
= .....
.................................,.......õõ__................., : ......
.............õ,õ........,........................õ:õ,õ
.......,õ:õ..:.:.:õ:õ...õ:õ:õ:õ..õ.... = = = =.=
....:.:. ...õ:õ.. :.:.:õ
..........õ.õ===::::....................,_.................. ..... = = , = = = = =
.............................õ..............................,.........=.: .
... õ...,.... ....: .....", : ........... .... ----, .., :: -:,:::.....::::::::,...:::::,.......,::::::õ......-..::::::::::::õ.õ......õ........õ..õõ..................õ.õ.......õ.............
.................:....õ..................õ............................õ:õ......
õõ:õ......õ, ,...:::: r,...
= ....... =:
,i,,,,:,:,::::.::.,:,..õ:;:::.:::,:::::oiiii;iii.::::=:::
lild'iNfti..e.::::iiiiiiiiiiiiiii..,.-i'i-ii.::'....
. - \ ...' . . \\ N...:.= \\ \ \ "-.
...,.... , .,.....\ \-\\ \ ..
\
\
:
N-..
\ ,,.µ......: ,,.
, \
, =
\ \ õ........ = .
\
µ..µ... .
...,. \ \\,.....
\ ..:.:.:.,.,...\
N.,.......,.
c::::::.:::::,,,,,,,Kii:::::::::w.,,,::::::*=:::::i::::
:.::":":....'.:N:::'::::::::::::::::::=':::::'= \ ' \ \ ....'.
:=>=:=::::,'.: \\:.µ,...0:::::::::::::::::::::'µ \
\ µ . .õ = ..........-:.:: , ...
. ''''''''''''':'''''''::':::::'::::'µ \ ii.:-.,\\==
.....................
..õ............õ......,..õ,,,,,...õ...........õ.......õ.....:;:..õ,õ.õ,:::::õ..
..,...õ..õ .
.........-'''''''''''...................==========¶=''''-''''',...:,,,......................:.:.:.......õõ,., ...... ...
- ----=======,.............,..........:.:.:..........x.:.,.,....õõ...,,..õ .
. = = = = = .... . . .....,.........................õ.. .
....................:.:,......,............,..õ:õ.:.:,,,,,,,,,,.....
.............. ...... :,..:
. ..".., .....:.:.s.:.:: ===:::", õ.. 5..i.::::=;:iiniii::::::::iiiii::::..W:i.g...i:EM-=.:,.i..:;i$-i.::::::=..iiiiiim=-:::::::::::::::.ft.::..:::::::::=:i:i:G.::.:.:.a.:.:Riiiii?:=:ii.:ii.,iAi.iisaR
iM:-., ''' ':':' :....,:ii.= ::.:.:: ::.;.: . = = ==
:.::.:=
::..:.:::Q::::.:..:::::...:.::i.::i::::::i::i:ii:::...:::::ww.:!..:=:mijmi:.::.
:Rm:..i0i:.i.:......!.:.!.:.!:;:wm,:==;=:.Ei.:i:.:.:=.:;.:=:=:::;..:;.ii.::.:==
=====:.:: .
2.:.... =.... ::.:.: -:::::::::.:.:..:.:,.............===-===== ....
10.01.71 .:17,*41110.:
,,,,i,:.,:,:,i,:,:,:,.:::::1:.::.:.,.,:.::.:oR:::ig:::ia.::.:i.:.:::
i:iii.::i.:..i::::::i:i:i:1:i:In::::::::limv::.:..,:.i....,::.:.::::.::::::::.:
:.::::::::.,.:g.:::,::-,::.,::.?:-,:..-,.:.,::.:]-=:.:..,--.:.,-,i,:.::::::, ....
. .... ..
. .................... .............. ........ ....
............... ............................... ..... ...=
......................................
............................................................,....,.....
= .....
..................................
....................................................õ..................,.......
.,......
- - - - - - =....-..... -....................................................-.......-....... . = .
= = = = =
............õ..................................õ...........õ.................õ.
....õ...............,, uptie did ..tiOterling, ..iR.:::.--mliii-.................-.....-......................:::-....-õ,.............?............................i..i............õ..................
...............................................................,........,......
......................... .,....:::.::....
.. . .. .. . . ... .
.............................õ:õ.õ....õ:õ::::õ.................................
..........................
...........................õ.............õ.õ....õ..............................
...................:õ.........õ...............,....õõ:õ..,.õ:õ..,.
' .=.. . .. .....õ,--. :"..1.;.-:::-"":_"1-;-",-""?-?-?....ifig........::,..........-:.:-:...i....i....,:,.....ii......:-.....':,..ii....:............i.:....i.,....A.6Ø4.-ili..0AttOrg....:g...i..i..i..i.???Eii.i::_:iiii..?..1-:,11iiii-iilili .................................................................¨.,. .
........ ... .........
--.-..................................
------ ...-----'\$µ..,.**..**......
-, ......,.....= = ..= '''Nµs '' ' Ni........a, \ N
= \ . .= ..-.=........::::::: ...= ...= .........-:::::::...:!..:::::::::: ..
= = , \\
.1...i...i...:...i....:..i....:..i...:1..:...i...:I.1.E.,!...E...:....E1.....E.
!..!..!!......i.i.!.
:=.:::::::::.:Mi'Mi:-.................... .....................
....................
!4M::Mini=:'.
.0::::::&a::::: ..:
.===:=..===:"..===='.======== .======= .======== .======= ========== .=======
========== .======= ========== :===== .======= :=====
=========::=====i=i...:========:=....:;:====:.:::.:====-=:=1:.:i.:===::::::.::=::::::::::....::":1:::::.:==:: .
'''''':::::: :%.'': ''':.' :.::M
''''''''...... \ \ ' '....................'...................................:.!..=-===========':!=!::....:,...!......1111112.1.::::::::::::::'..=:::::::::=..i....
1.=.i!,!!...........::::::::=...........::!õ.======:,=.;===.:,=.;====;!=====,==
==;==== =.==.:========;;:=::::::!..!.===!::::;;=.:::: .
, ......... õ . = = = ........
.....................,,, = = = = ::::::...................,,,, ::.:.::.......,:.,...:.:, ,.........:.:. ,....: ................
= ...===,.. õ ===,.....=.
................,...............õ.=========
....,.......,.....,.....=....,.............,.....,....... ...,....= ....
...=........ . ......... ..............,..,.......,..,..w.
..........................õõ.......,,,,,...............,=======
= ....... = :::,....:.: ...
,.........................., . = = = = = =
:........,......,,,,,,..........,..............,..........,.. =========. =
= == . ....
= .:.:., ,...:.,........ :::::: ...., ..,...
..,.............,,,,,,,,,..,..............======== .
....Or, [0018f Exa,tOptg.:4;.
::i=:?=-=:::,:j===i::.:": = .::'.i.=::11:i:.:-.1.1.:i0:-: :::::::. --',=:='"".::::.;'..=::::.i!l!i'.i!i.'i.';i!iill:I=iiii::iiP.":ii.i::::.!Iii=iit.
:K=i,.:if::iiiiii..ii' ii.-:.:==.i=.:i::...i::i::=:::.:.'=:,i.i.õi:.iii.::.,i,. - ,...:,,, ,.".:.'s:i?:i...-....ii::::i:-,...3'.i!.!:::.:.!.i::::T..!,,,:::::::õ::::.g::::::.:7:i;i;i1:1:.::::1-::::::.'"Ii!iii:g.::iiiiii1:,-1.Tõ::::::::; ,.:::,-...0:E.:* :'. - = -U.OPOt: i id .tighl*tii:Og., : ...:':?=:===
!!:.!::'.:=;'.=:=.i=titi:-..;$ ':',.;:-...:I.'...g.k.:.:.;::::=5; .:':"::!..=
==,-.,i:?:;i:K;:...-. .. :g::::'. =====, '"..':::::,::::::::::' . ,.:.: õ:õ..õ.õ......, .................õ.õ., .:.õ, õ:, .:.:.:.: ".:.:.: .....= ====== ======.
.,..........õ.õ.....,............õ........õ ........õ õõ.... ,...õ..õ ==
= = = = ..,...
. . .
.,õ.............,........õ............õõ..............õ.........., .......... ........ =õ.
.........................................õ......õ...õ ====== =.........õ
==== .....=
- - - = - - = - - = - = ====== = - - = - - ---. ..-- - = - -============ - - = ----... .................= - = = - = .. = ...
...
. ............. . ... ......... ....... ....., ....... .... ...
.............. ..................... ,......, .........õ.... ........ ...... iii...:
,i,.:.:.:: :=:::::: ,..:1::
........9.....%.:.i....s.:0.:::::::,i,-::::.:::::'.;-:.:,:-,.:..:.,=;:.::::::-:...,.,eii:iii.o:i:i:,,,.::::::::ii:-:i.:.s......::.::::::::::iii.:.i:::::
::::::: . . .
. õ, õ: ...... ........ . , ...õ,õ.õõõ,..õ......õ.....:õ...,....õ.....õ..:, ....õ....,...õ..,...:õ...õ:õ..:.., ..= .....= . = .
::::-.-------'",.....,::::*-----""----- = = ----=,,,,,,,,,,,,,,,,,,,, - - =
--- -,...A. ,,,....,..,...-, , = ,===õ=õ,. k.,.....õ....
µ.,,,.,.,. .. ,,,,,,. . .,....
. µ ... ..,......:,-,-,.,. ,,,,, ,, -: , ..:.:-....õõ,.........,õ.õ...õõõõ.......,,,,,........?........õ:-......::::::::::::........õ.õ:õ:õ...........................õ::::::-....-õ:õ....õ.........Leq: .,...:.:4,,::,3Ø,.:-õt,kat.r.= =ir.i:.: :.
)11::.iP':: H','::,::::=='''. \
N:i.....1....1....iimmii.::=:i::*:=:i::', ' ' ..".. .....- ..
...*:::::::::::::::::::]-:::::--'--- ==\õ..õ======,..õ.õ... -,---n. ===,=
....:-,.:..:.:::i.,,..., ...,...,...======:=::::i.i:::':;-....,=;.:0:.: '-.i.ii:i'i::,..,: \ ' "'1"="k'-.= =:i'igi::i .. ..
:::.......4.'ik \ =\
...,:,:':,..., \\: \ = . ====== ::.:.:=.::; . = ..,,...-.=:,....
?...................... ..:,..i,:g...=:::...::::-.........
::kiii:...;::''' \ =,,,,,...,, ,,..,...,.$,N. \\ \ ,,.'"
=====:.::: " õ..,. .... .... .. ...
........õ...õ:õõ:õ.õõ:... =
. ..... ....................... . ,. :.:.^
:
.......=...õ
.....õ,... , i...:::',..'= \ \ ..................., ,.,.
.... .. .... . . \ .
= . =
..... .....
'f=': == ..,..õ...õ....., ......
' VItl'is.= ',s, \ ..:A,..,mi:h.:\.
P-..'=-=:.2..:::::.:::::Zlit. \.i,'=& :iii....i.ii.ii: . ' ..ii2la&.. =-=', .-..v\
=
.1:õ..,1õ:..i..,:,.,;:.:.:.::..,,..,:i..õ, \ =
,, skks .= ,,,,, ,,= *=::= ::::=:-:.*. .=.: µ<4;404=X' !ii.....i.....iii ..0P1.....,:=.:3..0,,.;ii:i,:, ::.::-. ...
:,. \ - õ,,.,..õ.,.....õõ =,õ:õ:0,..- ...
'::::::,. .:=<=-=-,v,.=,.:',',-:.:-::,z..;vi,. ;:::::,:,.:::::
, \ ¨ - \,=,f.,..i?.,, -..::: õ:.i:.::::.::K:i =.:,... = : ::=:::::::::::, :-.. õ:. , \
*....:..i..i.i..i.i.i.iN \ ..... ............,...
:: .
- =iis.::,.
=
.... :::::,:õ, : =
: =:.i.::::]: .....*:::.
.........,........
.......:-..,--=::.:::.!.:.:1.i:i:.:=:i...
....õ...õ:====::,:::
... .......,................., ..........i:::i..,õõ.. ...::::::õ..:õ.. :.,õ: ====== - ....::õ,, ,,,,,, :"":: ...,. ...m...õ:.::::::g ::::::.:1::,i:.::--:::::m:::.:.:..i::i....:.::::?.?:::::0:iimiikk.:::::%::Roii;.1:,:=.::::::ii:i::
..igt.:ii::;":..::::::::it.:-:.::,:,:.,::::::,...:0 Upper h0. tIghtenf ng: , , :.,.,.. ....,,..
,.i.,,,..õ.,:,:.::,....z.7.,.....õ,...,:.....:,:,:?:.:...............õ, ,....... ....õ:õ... t.. . ... .. .... t..... . ... . . : .
= .....
.................................,.......õõ__................., : ......
.............õ,õ........,........................õ:õ,õ
.......,õ:õ..:.:.:õ:õ...õ:õ:õ:õ..õ.... = = = =.=
....:.:. ...õ:õ.. :.:.:õ
..........õ.õ===::::....................,_.................. ..... = = , = = = = =
.............................õ..............................,.........=.: .
... õ...,.... ....: .....", : ........... .... ----, .., :: -:,:::.....::::::::,...:::::,.......,::::::õ......-..::::::::::::õ.õ......õ........õ..õõ..................õ.õ.......õ.............
.................:....õ..................õ............................õ:õ......
õõ:õ......õ, ,...:::: r,...
= ....... =:
,i,,,,:,:,::::.::.,:,..õ:;:::.:::,:::::oiiii;iii.::::=:::
lild'iNfti..e.::::iiiiiiiiiiiiiii..,.-i'i-ii.::'....
. - \ ...' . . \\ N...:.= \\ \ \ "-.
...,.... , .,.....\ \-\\ \ ..
\
\
:
N-..
\ ,,.µ......: ,,.
, \
, =
\ \ õ........ = .
\
µ..µ... .
...,. \ \\,.....
\ ..:.:.:.,.,...\
N.,.......,.
c::::::.:::::,,,,,,,Kii:::::::::w.,,,::::::*=:::::i::::
:.::":":....'.:N:::'::::::::::::::::::=':::::'= \ ' \ \ ....'.
:=>=:=::::,'.: \\:.µ,...0:::::::::::::::::::::'µ \
\ µ . .õ = ..........-:.:: , ...
. ''''''''''''':'''''''::':::::'::::'µ \ ii.:-.,\\==
.....................
..õ............õ......,..õ,,,,,...õ...........õ.......õ.....:;:..õ,õ.õ,:::::õ..
..,...õ..õ .
.........-'''''''''''...................==========¶=''''-''''',...:,,,......................:.:.:.......õõ,., ...... ...
- ----=======,.............,..........:.:.:..........x.:.,.,....õõ...,,..õ .
. = = = = = .... . . .....,.........................õ.. .
....................:.:,......,............,..õ:õ.:.:,,,,,,,,,,.....
.............. ...... :,..:
. ..".., .....:.:.s.:.:: ===:::", õ.. 5..i.::::=;:iiniii::::::::iiiii::::..W:i.g...i:EM-=.:,.i..:;i$-i.::::::=..iiiiiim=-:::::::::::::::.ft.::..:::::::::=:i:i:G.::.:.:.a.:.:Riiiii?:=:ii.:ii.,iAi.iisaR
iM:-., ''' ':':' :....,:ii.= ::.:.:: ::.;.: . = = ==
:.::.:=
::..:.:::Q::::.:..:::::...:.::i.::i::::::i::i:ii:::...:::::ww.:!..:=:mijmi:.::.
:Rm:..i0i:.i.:......!.:.!.:.!:;:wm,:==;=:.Ei.:i:.:.:=.:;.:=:=:::;..:;.ii.::.:==
=====:.:: .
2.:.... =.... ::.:.: -:::::::::.:.:..:.:,.............===-===== ....
10.01.71 .:17,*41110.:
,,,,i,:.,:,:,i,:,:,:,.:::::1:.::.:.,.,:.::.:oR:::ig:::ia.::.:i.:.:::
i:iii.::i.:..i::::::i:i:i:1:i:In::::::::limv::.:..,:.i....,::.:.::::.::::::::.:
:.::::::::.,.:g.:::,::-,::.,::.?:-,:..-,.:.,::.:]-=:.:..,--.:.,-,i,:.::::::, ....
. .... ..
. .................... .............. ........ ....
............... ............................... ..... ...=
......................................
............................................................,....,.....
= .....
..................................
....................................................õ..................,.......
.,......
- - - - - - =....-..... -....................................................-.......-....... . = .
= = = = =
............õ..................................õ...........õ.................õ.
....õ...............,, uptie did ..tiOterling, ..iR.:::.--mliii-.................-.....-......................:::-....-õ,.............?............................i..i............õ..................
...............................................................,........,......
......................... .,....:::.::....
.. . .. .. . . ... .
.............................õ:õ.õ....õ:õ::::õ.................................
..........................
...........................õ.............õ.õ....õ..............................
...................:õ.........õ...............,....õõ:õ..,.õ:õ..,.
' .=.. . .. .....õ,--. :"..1.;.-:::-"":_"1-;-",-""?-?-?....ifig........::,..........-:.:-:...i....i....,:,.....ii......:-.....':,..ii....:............i.:....i.,....A.6Ø4.-ili..0AttOrg....:g...i..i..i..i.???Eii.i::_:iiii..?..1-:,11iiii-iilili .................................................................¨.,. .
........ ... .........
--.-..................................
------ ...-----'\$µ..,.**..**......
-, ......,.....= = ..= '''Nµs '' ' Ni........a, \ N
= \ . .= ..-.=........::::::: ...= ...= .........-:::::::...:!..:::::::::: ..
= = , \\
.1...i...i...:...i....:..i....:..i...:1..:...i...:I.1.E.,!...E...:....E1.....E.
!..!..!!......i.i.!.
:=.:::::::::.:Mi'Mi:-.................... .....................
....................
!4M::Mini=:'.
.0::::::&a::::: ..:
.===:=..===:"..===='.======== .======= .======== .======= ========== .=======
========== .======= ========== :===== .======= :=====
=========::=====i=i...:========:=....:;:====:.:::.:====-=:=1:.:i.:===::::::.::=::::::::::....::":1:::::.:==:: .
'''''':::::: :%.'': ''':.' :.::M
''''''''...... \ \ ' '....................'...................................:.!..=-===========':!=!::....:,...!......1111112.1.::::::::::::::'..=:::::::::=..i....
1.=.i!,!!...........::::::::=...........::!õ.======:,=.;===.:,=.;====;!=====,==
==;==== =.==.:========;;:=::::::!..!.===!::::;;=.:::: .
, ......... õ . = = = ........
.....................,,, = = = = ::::::...................,,,, ::.:.::.......,:.,...:.:, ,.........:.:. ,....: ................
= ...===,.. õ ===,.....=.
................,...............õ.=========
....,.......,.....,.....=....,.............,.....,....... ...,....= ....
...=........ . ......... ..............,..,.......,..,..w.
..........................õõ.......,,,,,...............,=======
= ....... = :::,....:.: ...
,.........................., . = = = = = =
:........,......,,,,,,..........,..............,..........,.. =========. =
= == . ....
= .:.:., ,...:.,........ :::::: ...., ..,...
..,.............,,,,,,,,,..,..............======== .
....Or, [0018f Exa,tOptg.:4;.
::i=:?=-=:::,:j===i::.:": = .::'.i.=::11:i:.:-.1.1.:i0:-: :::::::. --',=:='"".::::.;'..=::::.i!l!i'.i!i.'i.';i!iill:I=iiii::iiP.":ii.i::::.!Iii=iit.
:K=i,.:if::iiiiii..ii' ii.-:.:==.i=.:i::...i::i::=:::.:.'=:,i.i.õi:.iii.::.,i,. - ,...:,,, ,.".:.'s:i?:i...-....ii::::i:-,...3'.i!.!:::.:.!.i::::T..!,,,:::::::õ::::.g::::::.:7:i;i;i1:1:.::::1-::::::.'"Ii!iii:g.::iiiiii1:,-1.Tõ::::::::; ,.:::,-...0:E.:* :'. - = -U.OPOt: i id .tighl*tii:Og., : ...:':?=:===
!!:.!::'.:=;'.=:=.i=titi:-..;$ ':',.;:-...:I.'...g.k.:.:.;::::=5; .:':"::!..=
==,-.,i:?:;i:K;:...-. .. :g::::'. =====, '"..':::::,::::::::::' . ,.:.: õ:õ..õ.õ......, .................õ.õ., .:.õ, õ:, .:.:.:.: ".:.:.: .....= ====== ======.
.,..........õ.õ.....,............õ........õ ........õ õõ.... ,...õ..õ ==
= = = = ..,...
. . .
.,õ.............,........õ............õõ..............õ.........., .......... ........ =õ.
.........................................õ......õ...õ ====== =.........õ
==== .....=
- - - = - - = - - = - = ====== = - - = - - ---. ..-- - = - -============ - - = ----... .................= - = = - = .. = ...
...
. ............. . ... ......... ....... ....., ....... .... ...
.............. ..................... ,......, .........õ.... ........ ...... iii...:
,i,.:.:.:: :=:::::: ,..:1::
........9.....%.:.i....s.:0.:::::::,i,-::::.:::::'.;-:.:,:-,.:..:.,=;:.::::::-:...,.,eii:iii.o:i:i:,,,.::::::::ii:-:i.:.s......::.::::::::::iii.:.i:::::
::::::: . . .
. õ, õ: ...... ........ . , ...õ,õ.õõõ,..õ......õ.....:õ...,....õ.....õ..:, ....õ....,...õ..,...:õ...õ:õ..:.., ..= .....= . = .
::::-.-------'",.....,::::*-----""----- = = ----=,,,,,,,,,,,,,,,,,,,, - - =
--- -,...A. ,,,....,..,...-, , = ,===õ=õ,. k.,.....õ....
µ.,,,.,.,. .. ,,,,,,. . .,....
. µ ... ..,......:,-,-,.,. ,,,,, ,, -: , ..:.:-....õõ,.........,õ.õ...õõõõ.......,,,,,........?........õ:-......::::::::::::........õ.õ:õ:õ...........................õ::::::-....-õ:õ....õ.........Leq: .,...:.:4,,::,3Ø,.:-õt,kat.r.= =ir.i:.: :.
)11::.iP':: H','::,::::=='''. \
N:i.....1....1....iimmii.::=:i::*:=:i::', ' ' ..".. .....- ..
...*:::::::::::::::::::]-:::::--'--- ==\õ..õ======,..õ.õ... -,---n. ===,=
....:-,.:..:.:::i.,,..., ...,...,...======:=::::i.i:::':;-....,=;.:0:.: '-.i.ii:i'i::,..,: \ ' "'1"="k'-.= =:i'igi::i .. ..
:::.......4.'ik \ =\
...,:,:':,..., \\: \ = . ====== ::.:.:=.::; . = ..,,...-.=:,....
?...................... ..:,..i,:g...=:::...::::-.........
::kiii:...;::''' \ =,,,,,...,, ,,..,...,.$,N. \\ \ ,,.'"
=====:.::: " õ..,. .... .... .. ...
........õ...õ:õõ:õ.õõ:... =
. ..... ....................... . ,. :.:.^
:
.......=...õ
.....õ,... , i...:::',..'= \ \ ..................., ,.,.
.... .. .... . . \ .
= . =
..... .....
'f=': == ..,..õ...õ....., ......
' VItl'is.= ',s, \ ..:A,..,mi:h.:\.
P-..'=-=:.2..:::::.:::::Zlit. \.i,'=& :iii....i.ii.ii: . ' ..ii2la&.. =-=', .-..v\
=
.1:õ..,1õ:..i..,:,.,;:.:.:.::..,,..,:i..õ, \ =
,, skks .= ,,,,, ,,= *=::= ::::=:-:.*. .=.: µ<4;404=X' !ii.....i.....iii ..0P1.....,:=.:3..0,,.;ii:i,:, ::.::-. ...
:,. \ - õ,,.,..õ.,.....õõ =,õ:õ:0,..- ...
'::::::,. .:=<=-=-,v,.=,.:',',-:.:-::,z..;vi,. ;:::::,:,.:::::
, \ ¨ - \,=,f.,..i?.,, -..::: õ:.i:.::::.::K:i =.:,... = : ::=:::::::::::, :-.. õ:. , \
*....:..i..i.i..i.i.i.iN \ ..... ............,...
:: .
- =iis.::,.
=
.... :::::,:õ, : =
: =:.i.::::]: .....*:::.
.........,........
.......:-..,--=::.:::.!.:.:1.i:i:.:=:i...
....õ...õ:====::,:::
Claims (19)
1. A method for improvement of the tired look of human skin comprising administering citric acid or a salt thereof to a patient in need thereof, wherein said administering subcutaneous injection.
2. The method of claim 1, wherein said administering tightens subcutaneous fat via strengthening of wall proteins located in the hypodermis of the upper and lower eye lids to thereby enhance facial appearance.
3. The method a claim wherein said injection is in the form of one or more blebs or boluses.
4. The method of claim 1, further comprising measuring one or more improvements in the appearance a the skin with a measuring device.
5. The method of claim 1, wherein said citric acid or salt thereof is places in the superficial plane or deep plains of subdermal fat thereby causing skin tightening by connective tissue contractions, increased support of subcutaneous tissue, and providing tensile strength to protein strands below the dermis.
6. The method of claim 1, wherein citric acid or salt thereof is obtained from natural sources is synthetic.
7. The method according to claim 3, wherein said injection is administered to the eye lids of the patient in need of treatment.
8. The method according to claim 3, wherein said injection is administered to proximal to the orbit of the eyes of the patient in need of treatment.
9. The method according to claim 7, wherein said patient suffers from a condition of the eye lids selected from the group consisting of skin tenting impending skin tenting, lid laxity, skin sag, ptosis or skin overhang.
10. The method wording to claim 1, wherein said method is administered to a patient in need thereof either before or after the patient undergoes blepharoplasty surgery of the eye lids.
11. The method according to claim 1, wherein said method results in the re-positioning of fat and/or re-compartmentalizing of fatty tissue in the eye lids of the patient undergoing said method.
12. A composition for treatment of conditions of the eye lids of human patients in need of treatment thereof, comprising 10% of 3.2% sodium citrate buffer, 36.6%
isotonic water, 45% sodium chloride, 6.4% glycerol and trace electrolytes wherein said solution has a neutral pH.
isotonic water, 45% sodium chloride, 6.4% glycerol and trace electrolytes wherein said solution has a neutral pH.
13. The composition according to claim 12, wherein said composition has a viscosity to the viscosity of water at 20 to 25°C.
14. The composition according to claim 12, wherein said composition is used to treat certain conditions of the eye lids selected from the group consisting of skin tenting, impending skin tenting, lid laxity, skin sag, ptosis or skin overhang.
15. A kit comprising a. a pre-filled intravenous vial containing a pre-determined amount of either sodium citrate powder or a solution of sodium citrate;
b. an intravenous vial containing a prepared solution of isotonic water, sodium chloride, glycerol and select electrolytes;
c. an injector to reconstitute the sodium citrate powder or solution with the prepared isotonic water/sodium chloride/glycerol/electrolyte solution; and d. one or more syringes to administer the reconstituted components.
b. an intravenous vial containing a prepared solution of isotonic water, sodium chloride, glycerol and select electrolytes;
c. an injector to reconstitute the sodium citrate powder or solution with the prepared isotonic water/sodium chloride/glycerol/electrolyte solution; and d. one or more syringes to administer the reconstituted components.
16. The method according to claim 3, wherein said injection is given to the patient in a 10 ml dose.
17. The method of claim 2, wherein said method is used for cosmetic purposes.
18. The method of claim 17, wherein said method results in the reduction of the appearance of fine lines, wrinkles and pores of the patient being treated with the method.
19. The method of claim 2, wherein said method is used as a preventive measure in a patient in need of such treatment wherein said patient suffers from a skin condition of the eye lids selected from the group consisting of skin tenting, impending skin tenting, Iid laxity, skin sag, ptosis or skin overhang which can result in the impairment of the vision of the patient if said condition or condition are left untreated.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2017/024201 WO2018182562A1 (en) | 2017-03-26 | 2017-03-26 | Method of treatment of skin conditions of eye lids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3056919A1 true CA3056919A1 (en) | 2018-10-04 |
Family
ID=63678310
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3056919A Abandoned CA3056919A1 (en) | 2017-03-26 | 2017-03-26 | Method of treatment of skin conditions of eye lids |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP3600233A4 (en) |
| CN (1) | CN110582264B (en) |
| CA (1) | CA3056919A1 (en) |
| MX (1) | MX2019011603A (en) |
| WO (1) | WO2018182562A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20200016056A1 (en) * | 2018-01-05 | 2020-01-16 | Vivi Robyn Stafford | Method of subcutaneous aqueous citric acid injection non-surgical skin tightening excluding orbit |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB815517A (en) * | 1955-06-20 | 1959-06-24 | Upjohn Co | Dihydro novobiocin, its salts and other derivatives and pharmaceutical compositions containing same |
| WO1989007945A1 (en) * | 1988-02-26 | 1989-09-08 | Genentech, Inc. | Human relaxin formulation |
| CA2153553A1 (en) * | 1994-07-13 | 1996-01-14 | Hidekazu Suzuki | Stable lipid emulsion |
| CA2552442A1 (en) * | 2002-12-31 | 2004-06-30 | Avon Products, Inc. | Compositions and delivery methods for the treatment of wrinkles, fine lines and hyperhidrosis |
| JP2004292400A (en) * | 2003-03-28 | 2004-10-21 | Ichimaru Pharcos Co Ltd | Maillard reaction inhibitor and cosmetic composition or food |
| US7666829B2 (en) * | 2004-02-20 | 2010-02-23 | Human Matrix Sciences, Llc | Compositions for elastogenesis and connective tissue treatment |
| US7754230B2 (en) * | 2004-05-19 | 2010-07-13 | The Regents Of The University Of California | Methods and related compositions for reduction of fat |
| US20060127468A1 (en) * | 2004-05-19 | 2006-06-15 | Kolodney Michael S | Methods and related compositions for reduction of fat and skin tightening |
| KR20070027564A (en) * | 2004-05-28 | 2007-03-09 | 쉐링 코포레이션 | Injectable pharmaceutical suspension comprising posaconazole |
| US20070298005A1 (en) * | 2006-06-22 | 2007-12-27 | Marie-Josee Thibault | Injectable composition for treatment of skin defects or deformations |
| AR083847A1 (en) * | 2010-11-15 | 2013-03-27 | Novartis Ag | FC VARIANTS (CONSTANT FRAGMENT) SILENCERS OF ANTI-CD40 ANTIBODIES |
| WO2013033365A2 (en) * | 2011-08-30 | 2013-03-07 | Biorestorative Therapies, Inc. | Stem cell compositions and methods |
| KR101759694B1 (en) * | 2011-10-28 | 2017-07-19 | 인테그리티 바이오, 아이엔씨. | Protein formulations containing amino acids |
| RU2512801C1 (en) * | 2012-10-08 | 2014-04-10 | Ирина Юрьевна Юхман | Therapeutic eye balsam |
| CN105338988B (en) * | 2013-06-18 | 2019-05-14 | 山东省药学科学院 | Purposes of the xanthan gum in preparation injection beauty product |
| AR102869A1 (en) * | 2014-12-16 | 2017-03-29 | Lilly Co Eli | QUICK ACTION INSULIN COMPOSITIONS |
| TWI773641B (en) * | 2015-05-08 | 2022-08-11 | 日商活效製藥股份有限公司 | Aqueous suspension containing nano particles of glucocorticoids |
| US9744110B2 (en) * | 2015-09-29 | 2017-08-29 | Debra Louise Stafford | Method of treating conditions of the eyelid |
| US20180078621A1 (en) * | 2016-09-22 | 2018-03-22 | Kyoung Lack Lee | Composition for hypotonic lipolysis and manufacturing method thereof |
-
2017
- 2017-03-26 EP EP17902778.4A patent/EP3600233A4/en not_active Withdrawn
- 2017-03-26 CN CN201780090412.0A patent/CN110582264B/en active Active
- 2017-03-26 WO PCT/US2017/024201 patent/WO2018182562A1/en unknown
- 2017-03-26 CA CA3056919A patent/CA3056919A1/en not_active Abandoned
- 2017-03-26 MX MX2019011603A patent/MX2019011603A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN110582264A (en) | 2019-12-17 |
| CN110582264B (en) | 2022-11-11 |
| WO2018182562A1 (en) | 2018-10-04 |
| EP3600233A4 (en) | 2020-10-21 |
| MX2019011603A (en) | 2021-08-16 |
| EP3600233A1 (en) | 2020-02-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2690845C2 (en) | Method for stimulating hair growth and preventing hair loss of patient, substance therefor and method for producing substance | |
| Tran et al. | Vision loss and blindness following fillers | |
| Beatini et al. | Hyaluronic acid hybrid cooperative complexes and the BAP (Bio Aesthetic Points) technique: the new edge in biorejuvenation | |
| CA3056919A1 (en) | Method of treatment of skin conditions of eye lids | |
| US9744110B2 (en) | Method of treating conditions of the eyelid | |
| RU2703531C1 (en) | Method of correcting resistant skin defects | |
| Allen et al. | Intravenous procaine analgesia | |
| Akoglu et al. | A case report of episcleral artery embolism caused by hyaluronic acid injection into the malar area. | |
| WO2015126942A1 (en) | Compositions and methods for pain relief without numbness | |
| Hotta | Lip enhancement: physical assessment, injection techniques, and potential adverse events | |
| RU2817931C1 (en) | Method for rejuvenation of face and neck tissues in patients with signs of depressor hypertonicity causing aging | |
| Yanes et al. | Poly-L-Lactic Acid | |
| RU2826963C1 (en) | Method of carboxytherapy in treating patients with temporomandibular joint pain syndrome | |
| RU2666942C1 (en) | Method for treatment polyneiromyopathy of critical conditions in resanimatory patients | |
| RU2659959C1 (en) | Composition of the preparation for correction of skin defects | |
| RU2393823C1 (en) | Device for local delivery of medicinal solutions applied in ophthalmology | |
| RU2648181C1 (en) | Method for treatment of neurorethynopathy that is caused by heavy preeclampsia | |
| RU2498826C1 (en) | Method of treating patients with craniocerebral injury | |
| US20200016056A1 (en) | Method of subcutaneous aqueous citric acid injection non-surgical skin tightening excluding orbit | |
| Velthuis et al. | Fillers and Vessels: The Story of Arterial Obstruction after Cosmetic Treatment. J Angiol Vasc Surg 6: 069 | |
| Braccini | Medical rhinoplasty | |
| RU2625654C1 (en) | Method for local conservative treatment of myopia | |
| Vu et al. | HYALURONIC ACID FILLER INJECTION FOR COSMETIC PURPOSE: SKIN NECROSIS COMPLICATION AND TREATMENT-CASES REPORTS | |
| RU2257900C1 (en) | Method for treating progressing myopia | |
| Uspekhova et al. | Pulmonary Disorders After Injections of Hyaluronic Acid Fillers |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20220927 |
|
| FZDE | Discontinued |
Effective date: 20220927 |