1. Botulinum Toxin : A New Treatment Modality
서울대병원 피부과
서구일

2. 강의순서 보톡스개론 다양한 적응증 상품화된 제품 Basic Science 보톡스주름치료 메조보톡스
보툴리눔독소를 이용한 임상연구 사례들

3. Botoxology (보톡스학) 체계화된 시술의 필요성 보툴리눔독소 : 새로운 학문 영역 무림 고수의 비방은 없다.
신경근육질환(안검경련, 사경 등), 편두통, 주름, 사각턱, 다한증, 전립선비대증, 신경성방광, 치열….
체계적인 연구, 교육의 필요성
무림 고수의 비방은 없다.
Evidence Based Medicine
Reproducibility
체계화된 시술의 필요성
부작용을 최소화하는 시술

4. 보톡스 붐 미국 FDA 주름제거 승인(2002.4) 대통령후보까지 보톡스.. 보톡스의 장점
미국에서 가장 많이 시술되는 미용시술(2001)
Botox party
대통령후보까지 보톡스..
노무현후보(2002.4) 보톡스시술
“눈이 붓고 효과 없었다”
부적절한 치료 : 깊은 주름엔 반드시 Filler
보톡스의 장점
간편성 : 주사로 커피한잔 마실 시간에….
사회시간손실 없음 : 시술받았는지 남편도 모를거다.
확실한 효과

5. History of Botulinum toxin(BT)
Dr. Alan Scott : ophthalmologist
Animal study of strabismus treatment (1973.)
Clinical trials in human strabismus( s)
7,000 patients with 17,000 sessions
Neuromuscular diseases (1980s)
Blepharospasm, Torticolis, Cervical dystonia, Hemifacial spasm

6. BOTOX® 란? 박테리아가 생산하는 ‘보툴리눔톡신’이라는 단백질을 추출 정제한 제품 브랜드 (미국 알러겐).
Coke vs Coca Cola®
Aspirin®
작용메카니즘 : 근육 이완
개발배경 : 긴장성 신경근육질환의 치료
사시(사팔뜨기) : 1970년대
안검경련 : 1980년대(1989 미국 FDA 승인)
뇌성마비
사경 등
Ab Fab - perpetuates the myth
KEY messages include
BOTOX is a doctors only medicine and can only be administered by specifically trained physicians/ qualified medical practitioner.
People should ask if the doctor has been trained in the BOTOX technique
BOTOX is a naturally occurring purified protein that relaxes wrinkle-causing muscles creating a smoothed and improved appearance.
Side effects are temporary and reversible: can include mild headache, mild redness, tenderness, bruising, or nausea - most wear off in a few hours, at most a few days. Vary rarely spread of the treatment to surrounding muscles can result in temporary heavy eyelid.
There are no long-term side effects (10 years’ use in therapeutic conditions proves this)
If done properly, BOTOX does not leave you expressionless
It does not radically change your appearance or make you look like you have had a facelift. It won’t make you look 20 years younger, it won’t freeze your expressions - it softens lines and can be administered in particular areas only
I aim for a very natural look - it’s all about looking better for your age, not younger!

7. BOTOX®를 이용한 여러 치료법들 사시 편두통 사경 소아뇌성마비 안검경련 다한증
The earliest uses for BOTOX® were for strabismus (crossed eyes) and blepharospasm (a focal dystonia where involuntary contractions force the eye closed).
More recently it is being studied for migraine and early clinical findings suggest it may reduce the frequency and severity of these types of migraine and chronic tension headache.
It is used in cervical dystonia to treat abnormal positions of the head, neck and shoulders due to involuntary cervical muscle contractions.
BOTOX® is an approved non-surgical therapy in hyperhidrosis - excessive sweating of the armpits, hands and feet. Those afflicted with this condition can be forced to change clothes several times during the cours4e of a day. Hyperhidrosis causes significant implications to many dimensions of a person’s life due to its impact on employment, social interactions and personal life.
It is also widely used in conjunction with physical therapies to improve mobility in cerebral palsy patients under 12 years of age.
안검경련
다한증

9. “너무 자주하는 윙크버릇을 고치세요” <김운규 사장에 보내는 유서>
명예회장님께서는 당신이 누구보다 진실한 자식이었습니다, 당신이 회장 모실때 보면 저희 자식의 한사람으로 부끄러웠습니다. 명예회장님께서 원했던 대로 모든 대북사업을 강력히 추진하기 바랍니다. 당신 너무 자주하는 윙크버릇을 고치세요. 어리석은 사람이 어리석은 행동을 했습니다. 어리석은 행동을 하는 저를 여러분 용서바랍니다.

10. Use for Focal Hyperhidrosis
Use for treatment of focal hyperhidrosis
Bushara KO, et al in 1995
Although eccrine sweat gland is innervated by sympathetic nervous system, its neurotransmitter is the same acetyl choline as in Neuromuscular junction.
Gustatory, palmar, axillary hyperhidrosis

11. Cosmetic Use for Wrinkles
Blepharospasm patient in 1987
Published first in 1990 by Carruthers et al. Glabellar frown line
Carruthers A, Carruthers J. The treatment of glabellar furrows with botulinum A Exotoxin.
J Derm Surg Oncol 1990;16:83.

12. Other Cosmetic Use 사각턱(Masseter hypertrophy) 종아리 알통, 굵은 팔뚝 알통
메조보톡스, 보톡스리프트, Dermotoxin
Gummy Smile

13. 보톡스 종아리 윤곽술 Hypertrophy of Medial head of Gastrocnemius
동양인 특유의 미용적 수요.
동양인의 체형 ; 키가 작고 다리가 짧다.
“닭다리”
작용 기전 ; Disuse atrophy

14. 한국에서의 보톡스 (I) 1996년 1998년 1999년 8월 2002년 5월 2006년 7월 2008년 4월
보톡스(알러겐) KFDA 허가(수입 대웅제약)
1998년
보톡스(알러겐)가 희귀약품에서 전문약품으로 변경
1999년 8월
디스포트(Ipsen, United Kingdom, 한국보푸입센) 시판
2002년 5월
중국산 BTXA(란주생물연구소 제조, 한올제약수입) 시판
2006년 7월
국산 보톡스 메디톡신(㈜메디톡스, 태평양제약판매) 시판
2008년 4월
Myobloc(Solstice Neuroscience, 드림파마 수입) 시판

15. 각종 보툴리눔톡신 제품

16. Commercial preparations
Product
Serotype
Unit
Storage
Complex MW
Neurotoxin per vial(ng) pH
Form
Company
Botox® A
100U
Under –5 ℃
900kDa
<5 7
Vacuum dried
Allergan, USA
Dysport®
500U
In a refrigerator
<900kDa
12.5
Lyophilized
Ipsen, United Kingdom
BTXA®
Lanzhou Institute, China
Medytoxin®
700kDa
25/50/100
Medytox, Korea
Myobloc ® B
2,500U/ 5000U/
10,000U
5.6
solution
Solstice Neuroscience, USA
From Aoki KR, J Neurol 2001;248:3-10

17. Basic Science of BT(I) Clostridum botulinum Heat labile toxin
gram negative anaerobic rod
Heat labile toxin
8 serotype : A, B, C1, C2, D, E, F, G
A, B : commercially available
F : under investigation for patients developing immunity to type A exotoxin

18. Basic Science of BT(II)
Neurotoxin
Blocking of Ach release in presynaptic neuron at neuromuscular junction
3 Step
Binding to receptor on presynaptic neuron
Internalization (receptor mediated endocytosis)
Zinc dependent enzymatic cleavage of neuroexocytotic machinery
Irreversible permanent denervation

19. Mechanism of Action Pre-botulinum toxin type A:
ACh release results in muscle contraction.
Hyperactive muscle contraction characterized by excessive nerve stimulation, which leads to excessive release of acetylcholine.

20. Mechanism of Action 1. Binding
Binding domain appears to be heavy chain.
Selective for cholinergic nerve terminals such as motor nerve endings of neuromuscular junction and smooth muscles.

21. Mechanism of Action 2. Internalization
Internalized via receptor-mediated endocytosis.
Cleavage of the intracellular target SNAP-25 by the light chain temporarily blocks
neuromuscular transmission.

22. Mechanism of Action 2a. Intracellular target SNAP-25.
Potency and duration of
action of botulinum toxin type A may derive from action on SNAP-25.

23. Mechanism of Action 3. Blocking
Specific proteolysis of SNAP-25 by botulinum toxin type A temporarily blocks release of acetylcholine from affected nerve terminals.

24. Mechanism of Action 4. Resprouting
Chemical denervation of neuromuscular junction results in expansion of end-plate region and growth of collateral axonal sprouts.

25. Mechanism of Action 5. Re-establishment
Nerve sprout establishes new neuromuscular junction.
Muscle activity gradually returns over period of approximately 3 months.
Repeat injections required to maintain desired clinical effect.
Research continues on new re-establishment hypotheses.

26. Basic Science of BT(III)
Effect of muscle paralysis by Botox
Peak at 1-2weeks after injection
Sloop RR, Escutin RO, Matus JA, et al. Dose reponse curve of humanextensor digitorum brevis muscle function to intramuscularly injected botulinum A toixn. Neurology 1996;46:
Muscle atropy : 2-6 weeks
Recovery of muscle function
3-6 months
NMJ : homeostasis of synthesis and resorption
Axonal sprouting : new NMJ synthesis

27. Basic Science of BT(IV)
Method to evaluate the potency of BT
- LD 50 method 1 Mouse Unit(MU) : Amount of toxin that kills 50% of a group of female Swiss-Webster mice (18-20gm)
Toxicity in Human
- Toxic dose : Unit for 70 kg (40U/kg)
- Symptomatic dose : > 500 unit

28. Dilution of Botox ® Vial
Diluent Added (0.9% Normal Saline)
Resulting Dose (units per 0.1 mL)
1.0 mL
2.0 mL
2.5 mL
10.0 mL
10.0 U
5.0 U
4.0 U
1.0 U

29. Dilution of Botox ® Vial
Normal saline(preservative free)
증류수 : 통증 심함
Preservative(benzyl alcohol) : 역가 감소
If alcohol is used, let it evaporate
거품이 생기면 역가 감소
진공 상태 제거 : 10cc 주사기로 공기 주입
Gently introduce saline to prevent foaming, which may results in loss of potency due to protein denaturation(3cc syringe)

30. Antibodies to BTA 보톡스사각턱, 주름 치료에서는 문제되지 않음 호발조건 - 1회에 300 units 이상 주사
Not reported to occur in patients treated for cosmetic purposes or in doses of 100 units or less.
호발조건
- 1회에 300 units 이상 주사
Borodic G, et al. Neurology Jan;46(1):26-9
- 한달 이내에 재시술 할 경우
Clinical response to BT in patients with antibodies - Heterogenous

31. 표정근육
Direct insertion into dermis.

32. 표정주름

33. Anatomy of facial mimetic muscle

35. 보톡스 는 세월을 지우는 마법의 약 안검경련 환자에서 눈가주름이 펴지는 현상 보톡스주름 제거의 원리
Published first in 1990 by Carruthers et al.
Glabellar frown line Carruthers A, Carruthers J. The treatment
of glabellar furrows with botulinum A Exotoxin. J Derm Surg
Oncol 1990;16:83.
보톡스주름 제거의 원리
표정주름을 만드는 표정근육을 이완시켜 주름을 펴는 원리
피부가 약간 부으면서 가는 잔주름이 펴지는 원리
탱탱한 피부

36. 보톡스의 장점은? 간편성 : 주름 제거법의 혁명 안전성 확실한 효과 예방효과
“커피 한잔 마실 시간이면 시술이 끝나고 시술 받았는 지 당신 남편도 모른다”
안전성
수술이나 레이저박피에 비해 훨씬 안전하다.
설령 부작용이 생겨도 모두 원상회복
확실한 효과
자연스러운 젊음 “웬지 젊게 보인다”
예방효과

37. Intradermal Injection of Botulinum Toxin(IBT)
Mesobotox
Mesotherapy + Botox
Microbotox : Micro + Botox
Dermotoxin : Dermis +Toxin
Botoxlift : Botox + Lift
Intradermal botox
What Botox can do for treating expression wrinkles has been well documented; and since the subject was also covered in great detail during Dr.De Maio’s presentation, let me
focus instead on introducing Intradermal Botox Injection, a newly emerging technique in Botox application.
Intradermal injeciton of Botox is called by various terms such as Mesobotox, microbotox, dermotoxin, and botoxlift. Mesobotox is hybrid word from mesotherapy and botox. Microbotox comes from the small amount of botox(micro). Dermotoxin is .
Botox injected intradermally is called by various different names such as
Mesobotox, a compound word from mesotheraphy& botox;
Microbotox, to denote the micro doses of Botox injected;
Dermotoxin, a compound word from dermis and toxin );and
Botoxlift, a term first adopted at the Botox Expert Meeting held in Puhket in 2004, to signify the ability of Botox to lift and create an young and rejuvenated face

38. Intradermal Botox : Botox Lift
The full package of botox advantages to give a younger, revitalized appearance .
Anti wrinkle and skin tightening
Mimetic wrinkles, static wrinkles and pores
Lifting
Brow lift combined with elevation of lateral part of eyebrow
Masseter muscle reduction to create slimmer jaw line
Enhancement of sagging jowl
Technique: intramuscular injections in the glabellar region, orbicularis and masseter combined with multiple intradermal injections in the cheeks, jaw line and forehead.
Intradermal Botox or Botox Lift, as I would prefer to call it, brings together the best of what botox can deliver to make the face look younger and fresher and rejuvenated.
By improving static wrinkles, pores as well as mimetic wrinkles, IB leaves the skin looking firm, smoother and brighter.
Beyond anti-wrinkle effects, it also lifts and contours the entire face by helping to elevate the eyebrow, enhance jowls, and narrow the jaw line, to create a sculpted appearance.
For the purpose of achieving these simultaneous results, however, the technique I use consists not only simply of intradermal injection,
but involves a combination of multiple intradermal injections with the conventional intramuscular injection. Hence, my preference for the term Botox lift over intradermal Botox. 38 38

39. Elevator and Depressor Muscles of Face
Elevators
Depressors
Botox
Facial muscles can be divided into depressor m such as corrugator, orbicularis, depressor anguli oris m, platysma, and elevators such as frontalis and zygomaitcus m. As you well know, the face comes down, such as eyebrows and jowls droop with age. If the botox injected into these depressor m, then, botox can weaken these m. and therefore can deliver liftedcontour.
얼굴엔 depressor muscle과 elevator m.이 존재한다. aging되면서 jowl이나 눈썹 등이 밑으로 쳐지는데 Botox lift에서는 얼굴 전체적으로 보톡스를 주사하면서 특히 corrugator m, platysma m. depressor anguli oris m. 등 depressor m을 relax시켜줌으로써 처지는 것을 막아 젊게 보이게 할 수 있는 것이다.

40. Effects of Botox Lift Intradermal effect : Improvement of skin texture
Reduction of static wrinkles
Reduction of pore size
Intramuscular effects : shaping and lifting effect
Elevation of lateral part of eyebrow
Raising eyebrow
Lifting jowls
Widening of eye opening
Looking slender
We can classify the effect of botox lift into two part,
The first one is improvemnet of skin texture that we can get from intradermal effect, The skin looks shiny and smooth because static wrinkles and pores are improved.
The other is shaping and lifting effect that we can get from conventional intramuscular effect including lllllllllll

41. Advantages of Intradermal Injection
Botox can be placed in the lower half of the face.
No impact on the deeper muscles of facial expression.
It preserves the natural movement of facial expression.
Intradermal injection of BOTOX tightens the skin
Improves even static lines as well as pores.
Skin texture appears smooth and shiny
Botox injected intradermally in small amounts does not affect the deeper muscles of facial expression, meaning you can still make facial expressions after the procedure.
This means that we can now place Botox in the lower half of the face, in areas like the cheeks and around the mouth, with the full assurance that the facial expressions in those regions will continue to look natural. 41 41

42. Facial Mimetic Muscles are directly inserted into dermis.
Superficial part
Deeper part
Facial Mimetic Muscles are directly inserted into dermis. Facial Mimetic Muscles은 superficial part와 deeper part로 나뉘는데

43. Injection of BT into dermis.
Superficial part
보톡스를 superficially intradermal inject하면
If the botox is injected intradermally in small amount,
Deeper part

44. Paralysis of Superficial Part of mimetic muscles by BT
Then it paralyzes superficial part of mimetic m.
Deeper part

45. 임상연구시 고려사항들 디자인 Prospective, double blind 전향적 vs 후향적 이중맹검 vs 단일맹검
대조군 vs 군내대조군(intraindividual comparison)
자원자수
목적 : 효과, 동등성비교
군내대조군
효과 평가방법
객관적 vs 주관적(사진비교 등)
평가시기: 1주, 4주, 12주, 24주
부작용 평가
근육이완 관련 부작용 : 3-6개월은 지나야 원상회복
기타 부작용 : 두통, 알러지 등
According to the FDA guideline, Botox should be discarded within 4 hours after reconstitution with saline. However, as you well know, Botox is very expensive. And only a small amount of Botox, less than 1 vial, is required for the treatment of wrinkles for one person.

46. Kyle Seo, M.D., Nam-Jong Paik*, M.D.,
Effect of Refrigerated Storage Time on the potency of reconstituted botulinum toxin type A
Kyle Seo, M.D., Nam-Jong Paik*, M.D.,
Hee-Chul Eun, M.D.
Department of Dermatology, Department of Rehabilitation Medicine*, Seoul National University College of Medicine, Seoul, Korea
Thank you Mr. Chairman.
Good morning ladies and gentlemen.
I am from Seoul, Korea.
It’s my great pleasure to be able to give this presentation here in Madrid at the ISDS.
Today I’d like to talk about the Effect of refrigerated storage time on the potency of reconstituted botulinum toxin type A.

47. Storage Problem Problems associated with botulinum toxin type A (BTA)
FDA guideline : Botox(Allergan, USA) should be discarded within 4 hours after reconstitution due to loss of potency
Small amount of Botox less than 100U(1 vial) is required for treatment of wrinkles and spasmodic dysphonia.
Strategy
Treating several patients within 4 hours.
Difficult approach
Refrigerating or refreezing the unused toxin for later use.
Controversy on the effect of refrigerating or refreezing on the potency of reconstituted Botox
According to the FDA guideline, Botox should be discarded within 4 hours after reconstitution with saline. However, as you well know, Botox is very expensive. And only a small amount of Botox, less than 1 vial, is required for the treatment of wrinkles for one person.

48. Controversial results about the effect of storage time on the potency of BTA(I)
LD50 method
Degradation in potency after 12 hours refrigerated storage : 43%
Refreezing : 69.8% degradation in potency
Gartlan MG, Hoffman HT. Crystalline preparation of botulinum toxin type A(Botox): Degradation in potency with storage. Otolaryngol Head Neck Surg 1993;108:
Human model using EDB by Sloop RR
No reduction of potency of BTA after 2 week refrigerated storage
Sloop RR, Cole BA, Escutin RO. Reconstitution botulinum toxin type A does not lose potency in humans if it is refrozen or refrigerated for 2 weeks before use. Neurology 1997;48:
Drawbacks of this study
Only 4 volunteers
Only one time period : 2 week refrigerated storage
Despite the fact that many clinicians have used stored botulinum toxin after reconstitution, there have been a few reports published about the effect of refrigeration storage on the potency of BTA after reconstitution. Moreover, reviewing those articles, their results are conflicting depending on the authors.
According to the results of the mouse bioassay model, the potency of BTA decreased by 43%, only 12 hours after the reconstitution.
On the contrary, Sloop reported that no reduction of potency was observed in the human model, even after 2 week’s refrigerated storage. His human model employed EDB in charge of raising 5h toe. This muscle is one of the useless muscles in human. It doesn’t affect normal daily life. However, this study has some drawbacks.
To begin with, they only tested 4 volunteers, which is too small a number to induce a statistically significant conclusion. And they only checked one time period, after 2 week’s refrigerated storage.

49. Purpose of this study
To estimate the actual potency of BTA in humans regarding the duration of refrigerated storage after reconstituted with normal saline
The aim of this study was to estimate the actual potency of BTA in humans regarding the duration of refrigeration storage after reconstituted with normal saline.

50. Methods Design of study Storage time Volunteers
Prospective, randomized controlled study within group comparison
Storage time
1 week, 2 weeks, 4 weeks
Volunteers
11 in each time period (total 33)
Informed consent
We designed a prospective, randomized controlled study within group comparison.
We tested the effect of 3 different storage times; 1 week, 2 weeks and 4 weeks
11 volunteers in each time period, for a total of 33, were collected.

51. Methods BTA Injection method Insulin syringe(30G needle)
Botox ®(Allergan, USA)
Pooled due to variability between vials
Dosage : 2.5MU on each EDB
Control EDB : fresh botox
On the other EDB : stored botox was injected 1, 2 and 4 weeks later, according to their storage-time group.
Injection method
Insulin syringe(30G needle)
Injection site : belly of EDB, randomized
Injection point
Belly tendon method
Marked in order to evaluate the same point.
We used Botox ®, one of the commercialized BTA, and employed the human model developed by Dr.Sloop. 2.5MU of fresh botox was injected on one side of the EDB muscle as a control. On the other EDB, stored botox with the same dosage was injected 1, 2 and 4 weeks later, according to their storage-time group.

52. (picture)
Using the insulin syringe, botox was injected into the belly of the EDB. For future reference, the point of the electrode was marked in order to evaluate the same point.

53. Methods Evaluation method Statistics Nerve Conduction Study
Compound Muscle Action Potential(CMAP)
Evaluation period : 1 and 4 weeks after the injection
Statistics
SAS version 6.12
Random effect model
We performed the nerve Conduction Study in order to objectively compare the extent of muscle paralysis between EDB muscles injected with fresh Botox and those injected with stored Botox. Compound Muscle Action Potential was measured 1 and 4 weeks after the injection.

54. Result : 1 week-stored BTA%
This is the result of the NCS from the 1 week-stored group. The Y axis represents the ratio of CMAP compared with the baseline. The blue line represents the EDB muscles injected with fresh Botox. The red line represents the CMAP of EDB muscles injected with stored Botox. As you see here, 1 week-stored BTA showed less paralysis of EDB muscles than the fresh BTA. The p value was less than 0.01.
Week
Fig. 1. Comparison of complex muscle action potential(CMAP) of EDB between fresh Botox and 1 week-stored Botox depending on the time change (p < 0.01)

55. Result : 2 week-stored BTA%
This is the result of the NCS from the 2 week-stored group. In accordance with the result of the 1 week-stored group, the 2 week-stored BTA also showed less paralysis of EDB than the fresh BTA.. But the p value was marginally negligible,
Week
Fig. 2. Comparison of Complex maximal amplitude potential(CMAP) of EDB between fresh Botox and 2 week-stored Botox depending on the time change (p = 0.082)

56. Result : 4 week-stored BTA
This is the result of the 4 week-stored group. Similar to the result of the 2 week-stored group, the 4 week-stored BTA also tended to show a reduced potency when compared with the fresh BTA. But the p value was only
Fig. 3. Comparison of Complex maximal amplitude potential(CMAP) of EDB between fresh Botox and 4 week-stored Botox depending on the time change (p = 0.103)

57. Result : preserved saline%
Fig. 1. Comparison of Complex maximal amplitude potential(CMAP) of EDB between Normal saline(NS) and Preserved saline(PS) depending on the time change (p < 0.05)
Week

58. Koo Il Seo, M.D., Seun Yong Jung*, M.D.,
Is Botulinum toxin really effective for the treatment of palmar hyperhidrosis?
Koo Il Seo, M.D., Seun Yong Jung*, M.D.,
Hee Chul Eun, M.D.
Department of Dermatology, Seoul National University College of Medicine, Seoul Paik Foundation Hospital, Inje Medical College*
Seoul, Korea

59. 1. Treatments of Palmar hyperhidrosis
Previous treatments of palmar hyperhidrosis
Iontophoresis, anticholinergic drugs, sedatives etc.
Ineffective
Thoracoscopic sympathectomy : effective
Operation under general anesthesia
Complications
Compensatory hyperhidrosis, Horner’s syndrome
Irreversible

60. 2. Botulinum toxin A for the treatment of Focal Hyperhidrosis (I)
Blocking acetyl choline release at cholinergic synapse in the peripheral nervous system
Eccrine Sweat Gland
Cholinergic sympathetic innervaiton
Botulinum toxin : New treatment modality of Focal hyperhidrosis

61. 4. Previous reports on Botulinum toxin A for the treatment of Palmar hyperhidrosis
Injection method
Patients No.
Dose per palm
Sweat reduction
Duration
Author
120MU (Dysport)
26-31%
13 wks
Schnider SQ 11
5 months
28-48MU (Botox) 4
80% on 2nd wk
Naumann ID
4-12 months
Shelly
100MU (Botox) ID 4 ?

62. 5. Problems Small number of patients reported
No data on dose response relationship
Uncontrolled study
In case of ID injection

63. 6. Aims of the study
To clarify the dose response relationship of Botulinum toxin for the treatment of palmar hyperhidrosis

64. 7. Patients and Methods(I)
18 Palmar Hyperhidrosis(PH) patients
Sweat production > 50mg/min
Design
Double blind controlled study within group comparison

65. 7. Patients and Methods(II)
Botulinum toxin type A(BTA)(Botox)
Dose
control palm: 50 MU(0.75unit/cm2)
test palm : 33 MU(0.50unit/cm2 ) MU (0.25unit/cm2)
Injection under wrist block
Intradermal injection every 1cm2
70 sites per palm

66. 7. Patients and Methods(III)
Outcome Measurement
Gravimetric assessment of sweat production
mg/min
A4 Xerox paper
Assessment of hand muscle weakness
Hand dynamometer& pinch dynamometer

67. Change of sweat production after BTA injection (50MU)
mg/min

68. Change of sweat production after BTA injection depending on the dose
mg/min

69. Conclusion Dose : >50MU(?)
Maintenance period of effect : 1-3months(?)
Method of injection
Intradermal>Subcutaneous injection
Muscle weakness : none