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WO2000071089A1 - Regulation de la croissance de laine chez le mouton et les animaux assimiles - Google Patents

Regulation de la croissance de laine chez le mouton et les animaux assimiles Download PDF

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Publication number
WO2000071089A1
WO2000071089A1 PCT/AU2000/000487 AU0000487W WO0071089A1 WO 2000071089 A1 WO2000071089 A1 WO 2000071089A1 AU 0000487 W AU0000487 W AU 0000487W WO 0071089 A1 WO0071089 A1 WO 0071089A1
Authority
WO
WIPO (PCT)
Prior art keywords
skin
composition
treated
wool
sheep
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.)
Ceased
Application number
PCT/AU2000/000487
Other languages
English (en)
Inventor
Alan George Brownlee
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Commonwealth Scientific and Industrial Research Organization CSIRO
Original Assignee
Commonwealth Scientific and Industrial Research Organization CSIRO
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Commonwealth Scientific and Industrial Research Organization CSIRO filed Critical Commonwealth Scientific and Industrial Research Organization CSIRO
Priority to GB0129486A priority Critical patent/GB2368015B/en
Priority to NZ515655A priority patent/NZ515655A/en
Priority to AU45268/00A priority patent/AU777772B2/en
Publication of WO2000071089A1 publication Critical patent/WO2000071089A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D7/00—Devices or methods for introducing solid, liquid, or gaseous remedies or other materials into or onto the bodies of animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B18/203—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser applying laser energy to the outside of the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
    • A61B2018/00452—Skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
    • A61B2018/00452—Skin
    • A61B2018/00476—Hair follicles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent

Definitions

  • This invention relates to a method and composition for permanently reducing or preventing wool growth at a selected locality or localities in sheep and related animals.
  • the breech and/or pizzle area of sheep are treated in order to prevent the incidence of blow-fly strike and/or balanitis.
  • Blow-fly strike and balanitis are significant problems for sheep and wool growers. It is estimated that in Australia alone, losses exceeding $150 million per annum are caused by blow-fly strike and its containment.
  • Current methods for containing blow-fly strike and balanitis include crutching (i.e. periodic close shearing around the breech and hind legs), ringing of the pizzle and the widely practised treatment known as the Mules operation.
  • the Mules operation or "mulesing" involves the removal of a large flap of skin from lambs below the tail and down the hind leg using shears and without anaesthetic.
  • Pratt and Hopkins disclosed the use of a number of cryogenic, irritant, fixative and protein denaturizing agents. Of these, the protein denaturizing agents were the only compounds found to be successful and included 40% phenol and a mixture of 20% phenol and 50% orthocresol. Application was by painting 15-30ml onto the relevant area. In discussing the effectiveness of these agents, the authors noted a number of disadvantages arising from the toxic and irritant properties of phenol and cresol, such as the need to take special precautions to prevent injury to human operators and increased toxicity to lambs resulting from excess absorption through intact skin.
  • Australian patent specification No. 73793/91 describes a non-surgical mulesing method involving the application of a cationic compound such as a halogenated quaternary ammonium compound (e.g. didecylmethylamine ammonium chloride), which complexes with glycosaminoglycans present in the skin to form full skin thickness eschars which are ultimately sloughed to leave linear scars similar to those resulting from the Mules operation. While found to be effective in reducing blow-fly strike incidence, the method has not been widely practised because it appears to cause sheep a similar amount of pain to that of surgical mulesing. A further disadvantage is the risk of injury to operators.
  • a cationic compound such as a halogenated quaternary ammonium compound (e.g. didecylmethylamine ammonium chloride)
  • a quaternary ammonium compound e.g. didecylmethylamine ammonium chloride
  • the present invention provides, in one aspect, a method for the controlled ablation of wool follicles within skin of a wool bearing animal at one or more selected localities, comprising; treating said skin at said selected locality(ies) with a composition comprising at least one follicle-ablating agent and, subsequently, irradiating said skin at said selected locality(ies) with electromagnetic radiation of an intensity and/or wavelength to bring about the photodynamic ablation of at least a portion of the wool follicles present in the skin at said selected locality (ies).
  • a method for the controlled ablation of wool follicles within skin of a wool bearing animal at one or more selected localities comprising; treating said skin at said selected locality(ies) with a composition comprising at least one follicle-ablating agent and, subsequently, irradiating said skin at said selected locality(ies) with electromagnetic radiation of an intensity and/or wavelength to bring about the photodynamic ablation of at least a portion of the wool follicles present in the skin
  • the invention is hereinafter described in reference to the preferred treatment of the wool follicles of sheep, although the present invention is suitable for treatment of the wool follicles of other wool bearing animals such as goats and alpacas.
  • the present invention provides a method for the controlled ablation of wool follicles within skin of sheep at one or more selected localities, comprising; treating said skin at said selected locality(ies) with a composition comprising at least one follicle-ablating agent and, subsequently, irradiating said skin at said selected locality(ies) with electromagnetic radiation of an intensity and wavelength to bring about the photodynamic ablation of at least a portion of the wool follicles present in the skin at said selected locality (ies).
  • the follicle-ablating agent(s) may be selected from photosensitisers and substances which induce the formation and/or accumulation of an endogenous photosensitiser(s).
  • Suitable photosensitisers include porphyrin derivatives and analogues (e.g. haematoporphyrin (HpD) derivatives such as di-haematoporphyrin ether). It is, however, preferred to use a substance which induces the formation and/or accumulation of an endogenous photosensitiser(s).
  • HpD haematoporphyrin
  • the method comprises treating the skin at said selected locality(ies) by applying 5-aminolevulinic acid (5-ALA) or a derivative (e.g. esterified 5-ALA or 5-ALA conjugated to one or more fatty acids may show enhanced skin permeability) or analogue thereof.
  • 5-ALA which is readily absorbed by the skin, induces the biosynthesis in skin of an excess of protoporphyrin IX (PpIX).
  • PpIX protoporphyrin IX
  • Accumulated PpIX when irradiated with electromagnetic radiation of a photosensitising wavelength (e.g. white light or broad-spectrum red light), causes phototoxic damage or death (i.e. ablation) of skin cells including cells of wool follicles.
  • a photosensitising wavelength e.g. white light or broad-spectrum red light
  • the composition is preferably applied topically or intradermally/subcutaneously (e.g. by hydraulic or pneumatic applicators).
  • the composition preferably comprises a suitable carrier.
  • the carrier is preferably selected from diet ylene glycol monoethyl ether (DGME) and mixtures including propylene glycol and glycerol.
  • DGME diet ylene glycol monoethyl ether
  • Other suitable carriers include ethanol and isopropyl myristate.
  • composition may further comprise one or more chelating agents (e.g. EDTA and 2,2-dipyridyl) and/or other agent(s) (e.g. chlorophyll and prooxidants) to augment the effect of the follicle-ablating agents.
  • chelating agents e.g. EDTA and 2,2-dipyridyl
  • agent(s) e.g. chlorophyll and prooxidants
  • the wool at the skin locality(ies) to be treated may be removed, wholly or in part.
  • Methods for removing the wool include shearing, close clipping with shears (e.g. to a residual height of 1-2 mm), defleecing with epidermal growth factor (EGF), shaving and depilation. Degreasing of the wool and skin at the locality(ies) to be treated with soap or an alcohol wash is also advisable.
  • a period of time e.g. within 24 hours
  • electromagnetic radiation of an intensity and/or wavelength to bring about the photodynamic ablation of wool follicles.
  • the irradiation should be conducted between 2 and 15 hours, more preferably between 3 and 10 hours, after treating the skin with the said composition. Irradiation may be conducted using any suitable source of electromagnetic radiation.
  • the electromagnetic radiation will be of an intensity and wavelength to bring about the photodynamic ablation of at least a portion of the wool follicles by sensitising the absorbed follicle-ablating agent and/or accumulated exogenous photosensitiser(s).
  • the irradiation may be conducted using a monochromatic or polychromatic light source.
  • the irradiation is conducted using a source of light of wavelength 600 to 700 nm at a dose (i.e. intensity) of 100-175 (preferably, 150) J/cm 2 and a fluence rate of less than 150 mW/cm 2 , however, other sources of light may be used including ambient sunlight.
  • a source of light of wavelength 600 to 700 nm at a dose (i.e. intensity) of 100-175 (preferably, 150) J/cm 2 and a fluence rate of less than 150 mW/cm 2 , however, other sources of light may be used including ambient sunlight.
  • the method provides for the controlled ablation of a selected percentage of follicles within the selected locality (ies).
  • the method results in the ablation of at least 50%, more preferably at least 70%. of the follicles within the selected locality(ies).
  • the method results in the ablation of about 70- 85% of the wool follicles in the selected locality(ies).
  • the subsequent regrowth provided by the 15-30% viable (i.e. non-ablated or regenerated) follicles is insufficient for the occurrence of blow-fly strike and provides an advantage in that it prevents the development of skin cancers which might otherwise occur if 100% of the follicles were ablated.
  • the development of skin cancers is not anticipated to be a problem with treatment of the breech and/or pizzle area of sheep since these areas are substantially shaded from the sun by the sheep's body.
  • 100% ablation of wool follicles in sheep skin may be achieved with a composition comprising 10-20% (w/w) 5-ALA in a suitable carrier at pH 2.5 (unbuffered) or 4.0. Decreasing the amount of 5-ALA to 5-9% is expected to reduce the percentage of ablated follicles to 70-85%.
  • Varying the duration and/or intensity of the irradiation used is also expected to affect the percentage of ablated follicles.
  • a composition comprising 10% (w/w) 5-ALA in a suitable carrier at pH 2.5 (unbuffered)
  • an irradiation time of about 5 minutes (with white light at an intensity of 150J/cm 2 ) may be expected to achieve 100% ablation whereas an irradiation time of about 3 minutes may be expected to achieve 70-85% ablation.
  • the present invention provides a method for non- surgical mulesing of a sheep, the method comprising; treating the skin at the breech area of the sheep with a composition comprising at least one follicle-ablating agent and, subsequently, irradiating at least a portion of the treated area with electromagnetic radiation of an intensity and/or wavelength to bring about photodynamic ablation of at least a portion of said wool follicles in said treated skin.
  • a composition comprising at least one follicle-ablating agent and, subsequently, irradiating at least a portion of the treated area with electromagnetic radiation of an intensity and/or wavelength to bring about photodynamic ablation of at least a portion of said wool follicles in said treated skin.
  • the present invention provides a method for non-surgical pizzle ringing of a sheep, the method comprising; treating skin at or near the pizzle area of the sheep with a composition comprising at least one follicle-ablating agent and, subsequently, irradiating at least a portion of the treated area with electromagnetic radiation of an intensity and/or wavelength to bring about photodynamic ablation of at least a portion of said wool follicles in said treated skin.
  • the application of the method of the invention is not limited to the containment of incidence of blow-fly strike and balanitis. That is, the method may also be used for "wigging”, removal or reduction of wool from areas around the face, “crutching” (to prevent blow-fly strike and dags) and branding of sheep or other wool bearing animals.
  • the method of the present invention may also be used in conjunction with other wool treatments.
  • the method may be used as an adjunct to biological defleecing (e.g. EGF defleecing).
  • Figure 1 provides graphical results discussed in Example 2 hereinafter.
  • the figure shows that in skin samples taken from three sheep, the concentration of PpIX, a metabolite of 5-ALA thought to cause phototoxic damage or death to skin cells upon irradiation with electromagnetic radiation of a photosensitising wavelength, peaked between about 6 and 13 hours after application of 5-ALA.
  • the results suggest that the optimal time for irradiation is between about 8 and 10 hours after application of 5-ALA, however some other, empirical evidence from treated sheep indicates that these times are effective but that optimal levels in the follicles may be attained prior to this (e.g. between about 3 and 4 hours).
  • Example 1 Ablation of wool follicles in sheep Preparation of active agent:
  • 5-aminolevulinic acid ( ⁇ -aminolevulinic acid: 5-amino-4-oxopentanoic acid)
  • 5-ALA is combined with any suitable vehicle for topical application and absorption.
  • Tests on sheep employed a mixture of 20% (w/w) propylene glycol plus 80% (w/w) commercial sorbolene cream containing 10% glycerine (glycerol).
  • 5-ALA was tested at 5% (w/w) and 17% (w/w).
  • Skin was prepared for treatment by using a defleecing dose of epidermal growth factor, by shaving or by using a depilating agent such as thioglycollate.
  • the area was swabbed with 70% ethanol to degrease it and assist penetration of the cream.
  • Photodynamic treatment :
  • 5-ALA mixture was rubbed into the area briefly by hand and the animals then left for a period of 3 hours to allow the 5-ALA to be absorbed and metabolised in the skin and follicles.
  • the treatment area was irradiated with a white light source (e.g. a modified slide projector) containing a heat filter.
  • Light 600 - 700nm, was administered at a dose of 125j/cm 2 at a fluence rate of less than 150 mW/cm 2 .
  • the slide projector containing a 300W bulb
  • the lens was held 10 cm from the skin for no more than 10 mins. Spray anaesthetic was sometimes applied after the light was removed.
  • Tests were conducted to determine the period of time, following application of 5-ALA, required to achieve peak concentrations of the 5-ALA metabolite PpIX in skin. Since this metabolite is believed to cause phototoxic damage or death to skin cells upon irradiation with electromagnetic radiation of a photosensitising wavelength, it was reasoned that more consistent ablation of wool follicles in sheep could be achieved by irradiating the 5-ALA treated skin at a time when the peak concentration of PpIX was expected.
  • 5-ALA was formulated as a 10% (w/w) aqueous solution in 90% (w/w) DGME in the presence of various test compounds to measure their effectiveness in enhancing PpIX formation. These formulations were applied to clipped, mid-flank skin of several sheep after swabbing with 70% ethanol.
  • Skin biopsies were commenced immediately thereafter using a sterile 0.8cm human biopsy punch. Samples were taken at 2 hourly intervals for times up to about 20 hours. Skin samples were immediately frozen in dry ice and stored at -70°C until processed. Skin samples were then thawed, homogenised in aqueous buffer and PpIX extracted into an acid solution and then into an organic phase of ethyl acetate. PpIX levels were measured in a spectrofluorimeter using a set of standards of known PpIX concentration. The excitation wavelength was 430nm and emission was measured at 595nm. Results:
  • the success of the method of the present invention may, in part, also stem from an effect on skin structure, vasculature and other organs associated with the wool follicles in the treated area.
  • the ablation of sebaceous glands and skin microvasculature may affect both the ability of wool follicles to regenerate as well as the likelihood of the skin becoming inflamed and damaged in wet conditions that normally predispose to, or attract, blow-fly strike.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé et une composition permettant de réduire ou de prévenir de façon permanente la croissance de laine à des emplacements sélectionnés. Dans une application particulière, on traite la zone de la croupe et/ou du pénis d'un mouton afin de prévenir l'incidence de la myiase à calliphoridés et/ou de la balanite. Le procédé de l'invention consiste à traiter à l'aide d'une composition contenant un agent d'ablation du follicule, puis à irradier la peau avec un rayonnement électromagnétique dont l'intensité et/ou la longueur d'onde provoquent une ablation photodynamique. L'invention concerne également une composition contenant 10 % en poids d'une solution aqueuse d'acide 5-aminolévulinique (5-ALA) et au moins 80 % en poids d'éther mono-éthylique de diéthylène glycol (DGME).
PCT/AU2000/000487 1999-05-19 2000-05-19 Regulation de la croissance de laine chez le mouton et les animaux assimiles Ceased WO2000071089A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
GB0129486A GB2368015B (en) 1999-05-19 2000-05-19 Control of wool growth in sheep and related animals
NZ515655A NZ515655A (en) 1999-05-19 2000-05-19 Control of wool growth in sheep and related animals
AU45268/00A AU777772B2 (en) 1999-05-19 2000-05-19 Control of wool growth in sheep and related animals

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPQ0444 1999-05-19
AUPQ0444A AUPQ044499A0 (en) 1999-05-19 1999-05-19 Control of wool growth

Publications (1)

Publication Number Publication Date
WO2000071089A1 true WO2000071089A1 (fr) 2000-11-30

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PCT/AU2000/000487 Ceased WO2000071089A1 (fr) 1999-05-19 2000-05-19 Regulation de la croissance de laine chez le mouton et les animaux assimiles

Country Status (5)

Country Link
AU (1) AUPQ044499A0 (fr)
GB (1) GB2368015B (fr)
NZ (1) NZ515655A (fr)
WO (1) WO2000071089A1 (fr)
ZA (1) ZA200109639B (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003011275A1 (fr) * 2001-07-31 2003-02-13 Cosmo Oil Co., Ltd. Promoteurs de la croissance chez le porc et procede pour promouvoir la croissance chez le porc
EP1312353A1 (fr) * 2001-11-16 2003-05-21 Ecole Polytechnique Federale De Lausanne (Epfl) Méthode d'épilation
AU2002320806B2 (en) * 2001-12-21 2009-03-26 Heiniger Australia Pty Ltd Compositions
US8759396B2 (en) 2007-01-11 2014-06-24 Photocure Asa Use of aminolevulinic acid and derivatives thereof
US8822416B2 (en) 2005-03-15 2014-09-02 Animal Ethics Pty Ltd. Topical analgesic composition
CN107233303A (zh) * 2017-08-07 2017-10-10 苏州纳美特生物科技有限公司 一种氨基酮戊酸冷霜及其制备方法和应用

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63249577A (ja) * 1987-04-06 1988-10-17 浜理薬品工業株式会社 永久脱毛法、脱毛用製剤および器材
WO1996009853A1 (fr) * 1994-09-28 1996-04-04 The General Hospital Corporation Procede epilatoire
WO1997032046A1 (fr) * 1996-02-27 1997-09-04 New York Blood Center, Inc. Procede et composition depilatoires
WO1998048716A1 (fr) * 1997-04-29 1998-11-05 Galderma Research & Development, S.N.C. Procede d'epilation
WO1999004711A1 (fr) * 1997-07-25 1999-02-04 Thermolase Corporation Elimination des poils par agent photosensibilisant et laser
DE19832221A1 (de) * 1998-07-17 2000-02-03 Manfred Neubauer Verfahren zur kosmetischen Haarentfernung

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63249577A (ja) * 1987-04-06 1988-10-17 浜理薬品工業株式会社 永久脱毛法、脱毛用製剤および器材
WO1996009853A1 (fr) * 1994-09-28 1996-04-04 The General Hospital Corporation Procede epilatoire
WO1997032046A1 (fr) * 1996-02-27 1997-09-04 New York Blood Center, Inc. Procede et composition depilatoires
WO1998048716A1 (fr) * 1997-04-29 1998-11-05 Galderma Research & Development, S.N.C. Procede d'epilation
WO1999004711A1 (fr) * 1997-07-25 1999-02-04 Thermolase Corporation Elimination des poils par agent photosensibilisant et laser
DE19832221A1 (de) * 1998-07-17 2000-02-03 Manfred Neubauer Verfahren zur kosmetischen Haarentfernung

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Derwent World Patents Index; Class P34, AN 1988-335224/47 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7220779B2 (en) 2001-07-31 2007-05-22 Cosmo Oil Co., Ltd. Swine growth promoters and method of promoting swine growth
JP2003040770A (ja) * 2001-07-31 2003-02-13 Cosmo Oil Co Ltd 豚成育促進剤及び豚成育促進方法
WO2003011275A1 (fr) * 2001-07-31 2003-02-13 Cosmo Oil Co., Ltd. Promoteurs de la croissance chez le porc et procede pour promouvoir la croissance chez le porc
US8235974B2 (en) 2001-11-16 2012-08-07 Ecole Polytechnique Federale De Lausanne (Epfl) Method for hair removal
WO2003041673A3 (fr) * 2001-11-16 2003-08-28 Ecole Polytech Procede d'epilation des poils
EP1312353A1 (fr) * 2001-11-16 2003-05-21 Ecole Polytechnique Federale De Lausanne (Epfl) Méthode d'épilation
AU2002320806B2 (en) * 2001-12-21 2009-03-26 Heiniger Australia Pty Ltd Compositions
US8822416B2 (en) 2005-03-15 2014-09-02 Animal Ethics Pty Ltd. Topical analgesic composition
US8960128B2 (en) 2005-03-15 2015-02-24 Animal Ethics Pty Ltd Topical anesthetic composition
US9592318B2 (en) 2005-03-15 2017-03-14 Animal Ethics Pty Ltd Topical analgesic composition
US8759396B2 (en) 2007-01-11 2014-06-24 Photocure Asa Use of aminolevulinic acid and derivatives thereof
US10543272B2 (en) 2007-01-11 2020-01-28 Photocure Asa Use of aminolevulinic acid and derivatives thereof
CN107233303A (zh) * 2017-08-07 2017-10-10 苏州纳美特生物科技有限公司 一种氨基酮戊酸冷霜及其制备方法和应用

Also Published As

Publication number Publication date
NZ515655A (en) 2004-11-26
AUPQ044499A0 (en) 1999-06-10
GB2368015B (en) 2004-11-03
GB2368015A (en) 2002-04-24
ZA200109639B (en) 2002-11-22
GB0129486D0 (en) 2002-01-30

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