AP233A

AP233A - Chinese herbal extracts in the treatment of HIV related disease.

Info

Publication number: AP233A
Application number: APAP/P/1991/000304A
Authority: AP
Inventors: David Da-I Ho; Xiling Shirely Li
Original assignee: Cedars Sinai Medical Center
Priority date: 1990-06-19
Filing date: 1991-06-19
Publication date: 1993-03-07
Also published as: EP0491913A1; JPH05500824A; EP0491913A4; OA09651A; US5178865A; CA2064743A1; AP9100304A0; WO1991019507A1

Abstract

The invention features herbal extracts from ten (10)chinese herbal medicines demonstrating significant in vitro and ex vivo anti-hiv activity and their use for the diagnosis and treatment of hiv and hiv-related disease.

Description

II. BACKGROUND ART

Acquired Immune Deficiency Syncrome disease which results in life threatening coport malignancies. A retrovirus, designated human in 1(HTLV-III LAV)), has been isolated and identic this disease, tris vires as oee. s.ncwr tc te ^r and monccyte-macroDhages, and *t *s detectat'e ^; f’uid, se,^-. semen, sadva and cenfa' re-.cus

Ec~aC lc.-a' c* ^ed’C’Te. 321:1621-1625 1529 monccyte--acccage c.'eage se-ve as -mofta of the ce”.-associated virus in t9 bleed *s co

Characteristica'1y, then, AIDS ^;s associate! d cells, estecia'cy the nelpe-iC^te subset tea

Several agents have been retorted t immunodeficiency virus in v*t*~c. Among the age

-- ·?5^-,6 *s a oa.ndemic immunesuperess* jnistic infections and munodeficiency virus (Hived as tne etiologic agent of a-bcced oy 7 heloe ym.f'ccyt wne'e bleed, dasna. 'y-ca system t-ssue. c et al .. ID . -'t-cuch ce'1s o* tne ve ained wdhin DDL- ’ ce'Is.

a p-cg-essive ceo'edcn c* g tne C-l’A su-*'ace ’ar<s.

mnn-oit tne Growth o* tne h, s exh’t:t:nc

BAD ORIGINAL

	AP ο o 0 2 3 3
S2T6 are ^rc* 'ⁿ c'^;r^ca' JS6.	inc’udirg ’•'pav’’-iri, tidcvud'-e 1A2,
:^e 2’. 2 ’-3'reo/yr.,:'eos * :es .22.’ a~3 2:	η /- ·. , _ > _— . ; _ * _ . _ .·»

rce-'e-*:η-2, amo'*cen a-c 'soorincs'-e. ^nanc et a'., _ a^rc et ' ,9'-95 C15ΞΞ

P - ’ - 9 ~ ' Ο * Λ * ' * 3 r· - or- 3 * - ’ _	15' 19251: -o et al.. t ' .622-519
,^z ’ Q Q · M * ~ ·η ' ~ c * a g ” - o * *7 ’ ? ~ .	- · - C / ’ 0 £ 4 '' ' M ’ * “ r £ , ' p * a q - c -
=.393-332 1195'): H^;ts--a et al.. -::. '	af , <ad, 2c^;. .$A 52:1911-1915 a~c
52 : 7C96-'1CC <1955. 1926'; ^M’tsuya ec a'.	Ic'e-ce 226:l'2-l'c <155d' · ;<>-
c- < ----- :- = -- C-^; 71 ::-2-:	:--9252 '1955;; 9'tc' et a., -.’a-
22:151-190 ''1952'; ^ocenbaum ec a'.	, .a'cet i .A5C-451 <1 1935'.: Sa-cst'-
et al.. _a-cet '.1-22-1-52 11936): ie-c a	¹ - x , - , - <. - T - , * -J 2 χ - d / : . id,., d
'---r---r--r Oci- d · ’ .“3 m-

η θ r c ' 3 ** ' - » ί* 1 ⁿ 6 30Γ*33^~23 ζ ^Λ S 3 ?z. ,s ,a · c * -. ’ . - * * '

335Θ ** Θ* ·?** Θ3 3θ£ SuCv6 dSSci’ *0 36 ^336^ -,* «-,ρ -, _r

•ncaoac e c* concrete./ e '-mnat'rg -., -	n-ecc'c- = -cm one numon -esc. 51an;-e
et a'., .a^cet ' .363 1 1956'.· 2e Cle^cc et	a’ . . ;. Ine-. 29: 1561 -1 --=9
.1936. ; •'a-nca- et a'.. ,a.-.:et =.53-533	11955 ; «ecte’-oe’-c ec a'.. _ a - cec
i,159 1195'). In view of tne severity o*	tne AI2S situation and the tox'C'tv

and limited clinical e==icacy of the compounds tested tnus far, the scientists of the present invention have begun investigating the anti-HIV activity of extracts from Chinese medidna¹ herbs. Cnang and Yeung, A-t'v’ra' -eset’-cn

9:162-1'5 119SS': Chare et a'.. --c^;v^;--_:'	Οοςρ:-·-- 11:262-72 11959 ) ~-'s
Vnie’-'esa ·η Cninese he-cs was promoted bv	7n'n^cs= *’-¹ x' --o wn^-pin a ni-np- - =
cnese re-os have been, -eoucec to have arc	-'nfecc've activity and tc be *el'
cole-aced ov humans. - subset o* cnese -	r3S '‘Ο i'S2 333623 23 6X3’’j'i d3!i'’-

“IV activity, and a-e d'sc'csec he’-ei.

However, uh’-ese *0ik med'C'-o	e 'is cased iarge y cr anecdotal
ooservat'ons spanning fe cast seve-a¹ tn;	i.sancs c= yea-s. Hence, t-.e

effect; ve-ess cf tne me:^;c^;-a ne-bs -sed ;v fc'< -edic'-e θ’-act' tife-s -as

*or ore most oar-c, net see- s_ostant^;acec	cv sc^;e-c' = ic metnods. 2-eso't th's
lack o= scientific c-ocf. it 'S cuite oos:	vole t^ric so-e herpa' re-ee’es may
ng/CS’i 2	ΒΑΓ* ORDINAL

AP Ο Ο Ο 2 3 3 nave soef *^;c tne^aceutic action, as was c-cve^ tc be t^Ke case w^;f fe a- na'a-ia', cffosu, ana tf-acs eve” af--?. act'’.^;t_?. ^r'a,~a”, Iff

222:1345-1255 ( 1925). Consequent·;,·. «if -ega-d to tⁿe ocssf'e a-: attiv'ty a~crg Crr.nese ne-oa' exfacts, an .'test ^eec e^y,sts ‘c·*: 1 . fe • cent^{; ;} cat' on o’’ effect'.e ffH, foa' effects. 2' fe sfsta'f ve coo unentat^; or, by rodef sc'e'‘t^;'^;c etnocs, o* tee e’’ ‘ecf . e”ess c* fese fba' exfaots aga^;”st H?,, a-c 2' fe 'cef-* - cat'f c* e'fff/e = f'--I Chinese nefal extracts teat are 'ess texf than fe cu-erc'y ava^;'ac'e a~ -IV agents. The fetef fvef'er saf s’^;es fis need arc ccv'des -e'atec advantages as we''.

* Π *\a ->,□»· C *' * ,3 - _Λ ·; - jj - « - - r- ~

III. DISCLOSURE OF THE INVENTION t c nave

bi	teta' o* •^ty-s'x '56'·	- O’*	9 * ~ 2 ί ζ S ,	sc~e f A-f-	3 *· 5 . ~ ‘ _Λ -
3 rw * '	n/eotive o-ooe-f es and	tc	oe ‘f-ocxic	; ~ C' ' * ' 2 2 J 2	z ~ ~ 2- · - a
eened	for their anti-HIV acti	v¹1 y	usf,d in v^;t	ης technioues.	Gf fese
x (56)	herbal extracts, ten (	10)	we-e shown to	have potent a	n t i-HI V
in ifl	vitro experiments, and	two	(2) of these	ten (13) also	exhibited

aⁿt i-HIV activity in ρχ v¹’ vo exoe'-imef s.

'nese ten (1C) include f.e extracts on: Sample #1 f^; ff - s. w—ch can be 'ocatec i” westef, Soufef af Sef-a' >f: Sample $8 - I 'cost' com wa''^; f^;'. wf cr can oe feuf f Ncfef and South weste’'

Sn'f.a, and Sa'v'a n'* t' Of ⁿ - ;a. wnicn can ce 'coated nest a^eas c’ S”'”a:

Sample #21 - H · f ~u~ 'af f'atf. wn^;;h ca” oe '.ocatec f Eastef af Sc-fe*·' China; Sample #30 - Isatf f'ftff. which can be found f Cert”a' Sofa. Lf'ce’-a ~ar?rica. which can be located in nest areas of C.nin.a. and f' veenf b'Stefa. wnfn can be 'ceased in Nortnef, Eastern ano Soutnwestenn Cnf.a; Sample #32 - 3a' via m-lt'f f f a. which car, be -ocatec in most a-eas of Cr.ina;

BAD ORIGINAL &

Sample #35 - Ε ” y c' b e . -'bb^es · &

be

Sample #41 was te’

AP 0 0 0 2 3 3

-f'.'u. w-^;c- be ^rcund in Scub-e-n Cnina, ’idr, b-e’-r' “-sb-a'^a; Sample #39 - ; a b ? ? a - a p - a: ^: ~ ' Ce-t^a' ana Scub-weste’-n China a-b b-e ?.n i'' pp ’-es;

:~e:b ·:.·£. w.nipn pan be found ^;n mosb a-eas z~ C~--a aIb-be'b’-'a ~ a ~ b:' ° -¹ s' s. wn'bn aa- be 'bbabeb

-b-al C—:a a-b Cb.bnen Sample #44 - I a be b: a b eb ^; n - z: b a-eas ~^f ‘’b-b-e’' C' a, a nc la'·'³ be 'bbab-b ^;n ~a;b a-eas z' C.nina; a-b Sample #49 ban be ’pcabed ~psb a-eas z* Ch^;na. ab Sccbe*'a-·a e 'baabea 1- ‘ΐί’Ρ·'β’·η,, tsesbe’' anc Ce^b-a' C- na. a:

TAB!

SAMPLE	NAME OF HERB	CLASSIFICATION	MAJOR LOCATION
#1	Cppb’s b-'-e-b’i ’•a-'p.n		f-esbe. Cbub^e’”' a Cenb'a' C-?na
#8	L i gusti cum wa* 1 i -:ni i ranch and	Umbel‘i ^ferae	Northe-n and Southwestern Ch-na;
	Salvia mi 1 tiorr.ni pa 3unge	Labiabae	Most areas of ChOna
#21	Il 1icium lancec'abum -.C. Serb- or I'' ^; c · um ''ε—..' 1 · e's	11¹i b-aceae	Eastern and Sout-e” C'i'c
#30	Isab's binebe*’’ an Isab^;s 'nb^;bbb-;a ^romp.,	2 ** j 2 * “ 1 ” 3 *?	C 2 z z ' ni
	_b,ni ze^s. :zzz-' :a ~urp anc	Cac-i-b'-iaceae	Mς * ; · c 3 c ~ · * * - 2
	L· 9 * y¹ r* ; * · ··-^*~ ·· 2		V“ · r- r· Z — i“ * --1 r~ r- -,
		~ -

#32 a 1 v· a j nee #35 E-ycibe

Convc'v„laceae a'wa-. Capa- , Indonesia anc iJp’-b-eAusb-a’'a

BAD ORIGINAL

AP Ο Ο Ο 2 3 3


#39 Aoantnocanax A-a’fceae g-aci 1 ^atyl us H. W. Smith	Sen fa' arc Scuthueste-- f'-a. 'fsines
♦ #41 Eostau-us comestfus Eov*ne ono'e'p	M e - d-c.3r - » ^r z i_-J- — J </ ·
7 —> p ' 2 — 2 S?jte:‘^,a^ru oaica'eus’s _ao^;atae	‘<^r‘22’_t 9225*- 2 9 2 2 ' C 7 2 , 2 A 2 Γ' 2 2
♦ #44 Sadia ~^;'f o---^;oa .ao<atae	M - - * ; - f - - Γ
I-ula ne'e-* f .. SfOOsitae	f-f e-r. No-t-eastfand Ncrf-este-- S·—a
* #49 .dnice-a jacc-ica Safi'ol aoeae f u-o a-c	Most a-eas of f'-a
t__tr . ύ’-.ο -z _c e.v S -Id	f-f-e-n, «estey a';

COrTi^T'SinC 72^5 2.72^r 2^η5 '· 1 7 2 *2.

r

in tne context o' the -rese-t soeci-ioaf'c	f CHE is uses to -e-'e- to
2ⁿv S292'92 2”* 2^7 2* 2^9 ^5^22 22^^22252 22279	« 2 2 ^r 2^2^2 2 2 ^^, · ' 5 * ’ y
a facfcn oompr-sing a ora-racc'cgf al d actde age-t	. wreff a ccroore-t. a
combination of comocnents, a bio'ocioai metabolite, a :	^9^^722^75 279^^02 2
combination of the above, that exhibits *n vifo anc/c	- ex v'vq anti-HIV
activity. Since the precise chemical composition and ;	pharmacologic mechanism. z^f ’
the CHEs has not yet been e'ucidated, it d possible d	'at tne anf-dV af dfy
may be Cue to a sincle CHE comccnent, a comoination o*	* η Γ /•.-.ι«·πΛΓΐρηζ Γ·, r* * - Λ

in tne context o' the orese! soeoi-ioaf'c	f CHE is uses to -e-'e- to
2ⁿv S292'92 2”* 7 2^2 ^5^22 22^^22252 22279	« 2 2 ^r 2^2^222^^, · ' 5 * ’ y
a f-actfn oomp-'sing a ona-macclogf ai' y actde age-t	. wetf a ccroore-t. a
combination of comocnents, a bio'ocioai metabolite, a :	^9^^722^75 279^^02 2
combination of the above, that exhibits *n vifo anc/c	- ex v’vq anti-HIV
activity. Since the precise chemical composition and ;	pharmacologic mechanism z^f ’
the CHEs has not yet been e'ucidated, it ⁴s possible t*	'at tne ant’-HV act'vfy
may be Cue to a single CHE comccnent, a comoination o*	* η Γ '••-‘.Ι-ηΛ/ίρη^ς Τ * - Λ
oiclocic metabolite on cerivaflve tnereof.

Ey tne se-~s HIV, ant ’AIDS-related virus ^;s neaf tne oo~~:-'_. designated -IV se-ies '-fa- '~~..-:f'’ z~ e-oy v^;,-js) · oa'led .-.

dfld A27, 2^2 S252'9S 2^5^52^. 22 2222^292 * 2^5 ^22^22^2292 ^5^9^2^252.

f‘

Similarly, tne fe--s HIV-related disease anc AIDS-related

disease snail -e^er to any ''ness f sv-fcme, causes	' 2 * 922 ' 7 2** ' 2 * ·“ - 2 2 ' ♦
oy HIV O’* AICS-nelated d-us, fodo'-g out -,of 'ff	22 :^522^2 A’-'OSe
source is funoal, viral and/θ’- oacte-^;ad

BAD ORIGINAL ft

AP Ο Ο Ο 2 3 3 's therefc-e ar co;e:: ο· tne present invention tc eⁿ d w -1 n H.. vq ν' z'Z st-dies ices (Ί) ca'celated ’c- eat' ha-nacblcci:a' creca^ac· c~s a:

Z-Zs a: t'e-aneut'd agents · sts ν” = .0 st-t'es. inc'udir.g tne tne-aceut'c

s.geest s-at these C.-iEs wi'' ce _se*-' ^; : · v ~ a-t’-H-V agents. Tne cra-raco”ccica' creoaratic’s may ccta'c ca·—a::'cc'ca' active inched'et a'cne c ir. acm'.xt_re *'tr ar. acccc^r e’C'C^;e'c cr ca-'-'e. arc acm^; ~' ste-ec tc the HIV infected nest by e-te a; fa t -ettal , arc ca^e'ce^a'. s-C” as : rc-ace”' tenea' intrafsc_' 't-axefus c- subcutaneous route. me fa-naccleg'ca' agent may a'so .

ac^-''sce-ec 'n comoinat'cn w'c- a s_cc'e~e~:a' anc'vfa' acent, a^{r ;}nn:

V*a s-cccs':· es or arscies.

· S 2 - C t 2 β * 2 2 ^; 62 2 7 2 6 ' ~ v 6 2 2 ' Q 22 L S 6 2 CHE 2 2 ~ 2 2 Γ. 6 Γ 2 2 *“

CC^C'^iC’2^ C * 2 Η E 22722^6^22, 2 2 ' 2 ' 2 2' 2 ’*62i22'*26. ΐ 2 6 ’ 7 2 2 ' V 6 ζ - i »· c · * *· 22“2‘~22 ' Σ~ 2* 2^6 62276, ' 2 2'^,3**“2 22' 22 ^; 22* 2^622^2 2 ' *2** 226 2^622^-^^2 '

HI'.-'-e',atec illness in injected osts.

It is a further object c^£ the invention to use the CHE, its ac:iv< cnent or combination of components, a biological metabolite, a derivative tne^eo’. f a combination cf the above. a'fe or conjugated tc a label. ⁴r a :e Cafes': C <7 elated '''esc. Sucn a test cc.'c :

escert test, base: _oo a Σ-Ξ¹ s cacaCty to bine C.f tne -I. le arC-iCctytic art'tcdy cer-vec 'c- t-ie C-Z.

' a 'urtne eject tne ^/e't'c to use a S-Z. a Z-Z on o' 1“Z cftfecs. a c'c'cg'cal metabolite, a a ccnbinat'cn o*' Ce above to o^roduce a vacc'ne. Znce has bee- cete-m’nec, cfet immunc'ogic tefCcues o produce s-C a vacc'-e.

θ $ o 2-2 2 2262 2 2 * 6 2 2 S λ * 262276 **622' ' » ·2 2 2 2 ** 6 2 22 2 ¹— ^c

d'agnos	* ’ ~	test f
an ' — j	rf	uc escer
inject-	p ~	ce'ls or
· c		It C s

d 6 2 * . 2 2	,·

226 2HE	¹ e	active s
222'2 2	e -e	' e d u ο o
ski 62		fese a the art

r.₅/-’

BAD ORIGINAL $

AP Ο Ο Ο 2 3 3

IV. BRTEF DESCRIPTION OF THE DRAWINGS ,ne prese-t mve-tic- w he cesc-ioed in co.--ect'or with actcmcary·¹-g crawirgs it w-ic.n:

Figure 1 ·$ a co~ocs^;ce g-aor ceo'ct^;-g :ⁿe mmim -esults for each o' t-e te- CHEs agamst ue lac mc'ate 213.

Figure 2 m a cc~ccs'fe t-aor cec'cmm me act'v'tv c/ ’/a teE-Es agamst tee iaco-ato-y isolate, Hlv-l AC.

Figure 3 ^;s a ccmcos'te g-aoh depicting the -eut-a i cat' or. assa results fc- each zf cne te- CHEs agamst t-e lac mo'ate -1.-2.

Figure 4 'mmates am tmoa-es te cemmt -1. -e_ma cm. m

3Γ CCSC

2HE #3C’ f;

Figure 5 m'usmates arc cemoa-es me cercem -1. -em.-.·.' each or se-en seoa-m.e ο''-'ca' mc'ates m t-e m-us. Figure 6 ^;'lust-ates arc com.pa-es tne cerce-t Hlv neutral

Figure 7 -.st-ates am com.oa-ec t-e cercem -1. r.eut-al each of sever seoa-ate mirica' isolates of the virus.

Figure 8 illustrates anc compares the perce-t HIV neutral EHE #32 for each of sever separate clinical isolates of the virus.

Figure 9 illust-ates ard comca-es the percent Hit neutral each ο^- seven seca-ate c'mica' 'solaces o^; me .--us.

Figure 10 i'lust-ates arc ccm-a-es the ce-ce-t -IV -eut-a each, c* seve- seca-ate ο''-'ca¹ mc'ates m’ t-e vmus.

Figure 11 i'l.smares arc compares me ce-ce-t -1. -eut-a 2 * p 2 £ h 0* S ~ V ~ ' * ί £ z ' ' S C * c * ^{ώ f} * * “ y · ** - < c

Figure 12 illust-ates arc comoa-es t-e ce-;

m- earn of sever seca-ate c'mica! molates o* t-e v'-us.

Figure 13 i'lust-ates arc coroa-es tne ce-: m- eacr o* sever seca-ate c'mica' molates m icam'or m

1HE *35

BAD ORIGINAL

-: -2516

AP Ο Ο Ο 2 3 3

Figure 14 ^-s a composite c-ao- oet'ct'-; t^e dec-ee o^f <7 -ec* ·' cat' c- -rrdr:·;* exoib'teo ο.. 2“2 «22.

Figure 15 '''ust-ates a-o co~:a-e: toe a-t·-<·.' activity z^e 2-5 s *21. = 22 a-d «79 :--c-^;cal'y -o/etted -9Ί11Ξ ces.

Figure 16 ^_s a oomocs^;te c-ac- ceo'dt'-c eat' 2-5's oe-te-t neut-a'*oat'cn o- . 1115 -everse t-ansc'-iptase aot^; v· ty.

Figure 17 -''cstoates a-d co-oa-et t-e -. ~ v ? -.-t^;--'l, aofivtj 2.-E =22 ' t-e pe-to-e-a' o'ooc ncoc-udea- te'ls '^:5^M‘-s) a-d plasma c* t—es 12) patients.

Figure IS ^;''ostoates a-: :p~.pa-es toe ' * - aofi--I7 sett v'P.

V. DETAILED DESCRIPTION oe 'C''o-.i-o detailed desa-'pfio- aoc pnpoeou-es a-e prpvioet 'Tjst-ate t-e pr-'ip-p'es o* t-e ^;-ve-t'o-. '-ey a-e -ot. -owe.e-. ^;-teoc ' T t ’ ** v β r t' C r , e^γ terCS £ z t r e * Z t C S 6 C * t r 6 “ * ά ' Π

A. Preparation Of Extracts 'ne Fi^fty (56) subject he-os *e-e opta'ned from Chi pa-eote-a: use.

o-eseot '-ve-t: on ca- oe o-e-a-ec --0- to-ooed^-es set torto ;<>, -- aov o-cao·' ' · * Γ) *.- ? * s * -'prop mrc ' oe-o p-'eoes e^;o-t ''te-s ISLl c⁽ wateooo-s, and toe-, coil _-cs- -e^flox *o- one t tn-c_c- a C.-tEuo oe~o-ane -ilte-. a' ao.o maio.ta'o toe o/.xt_-e at -oc.n tempe-atj^r 'oa :n e x t - a:

a-, t-e ext-acts o* t-e • c ^K, y j * ' ' ' C * Π e s*?cec^:J^re.

£ £ Ο β < t r e C~Z : e ** e t j ~ e ’2*“ £' x tc e' sz ? β C ά Γ, t t^π 6 β X t 3 C t, * ' ' Z 6^r;c ere ' ter f LL J.

• r, c . . .-c e - . c „

22', -0-<

-g/t5'6

BAD ORIGINAL Γ

AP Ο Ο Ο 2 3 3 ter and concentrate the exfact to ere '^;te^r ' L-' as above.

'ece;

s etra-c srer;

(2) ira-toa :e-f ated extract.

afcal-extract mixture ^s xe (5; m^; ⁷o tre fi'le^ed extract, act 'ά'ΐ θ \ί*⁷ '* COrcer.trdt’C”' C* C3i ^r·CS ' :es, ce

B. Determination Of The Subtoxic Concentrations Of Herbal Extracts tc> · ;:. st.ces ^e-e te-*?—e; tc effe fat t'e etc, ce acc-'outec tc tre ‘-ct:-—-ate cect-^cf··.' s^; tre

C-E. Ff t-ese st-t'es, fe sta-ta-d aofatfy tesfrg were followed. Cra.-g et al.. Artiv·-·?.' ^esea-f 9:16 > n r * n »

P* A '·' --easel' s. MN ^z 1962;.

Briefly, the CHE extract tc be tested was diluted two-fcld serially •edium. To 0.2 ml of the d'.'uted extract, 0.8 ml of a ^fresnly prepared H9 suspension was added. (The H9 cells had been obtained from the American ? Cu'ture Collection (A.’.C.C.).) This was core f duplicate; and a medium :-c' was 'nclucec in exe-x assax. T^rms med’um control : n cel ;e same H cell susce-sicr acted t:

i urn cf f c > tens' ste medium; and the s

Ά ri.ee f fc' was dene o' e ce''s ' nor xtC nse ! SC cu tu^e -as courted -'f a -enaevtf ese- οχ dxe exo'usio^r t c* exf act-f eated cu'tu-e was 2 S.C. oe’ow the mea- c* fe mec'„~ o', tre extract-treated c-'tfe was co-sice-ec to· snow evidence c* tcxicity. The n'cnest conce-traticn o^r' an e/fact which sr.-wee no exfe-c· totox'· o’ty was ta<e- as fe sustcx'c ccnce-f at^; on, or nax^;~-m tde-ated

IkTC;. ’re MTS's fo- tre ter (1C) C-Es ex-'oiting arf-HlV act’xity a-e 'osed in ’able ’’ which fo~ws:

BAD ORIGINAL &

AP Ο Ο Ο 2 3 3

TABLE II * ” ~ ' ρ r- ς - - - * C Ο ‘ Μ

CHE

KTD(jl) r'V ^s U3 *33

C. Neutralization Assay lfi V ' t-e^-- ^M’0s.

s.-'-pP^OC

I3IS had been obtained from θ’-s. Popovic arc Gallo.) Emoloying a standard neutralization assay, whicn assay is described in the literature, HIV exo-ess'cwas detected by p24 production in the culture supernatant. Ho et al., Science kF

139:1021-1023 (1938); and He et at.,

51:2024 (1987).

:>oec'-':c -y, tre t-e H’V-1115 isolate was c'aced contact *^;tr 1 X

-cm a-te- tne CHE rde’· ’-vest'-aticn was acted at .vas t-e- 'o^?lowed -:- save- ca.-s a-c csse-ved -c- s' edt've doses mar vrsen measured by the modusd's- ο* -IV deemed to nave ant’-HlV activity dcmoa-ed to aortrcl cultu-es.

.p.. a._;„ ._va,.

?SS 31 •eaessarv

-escect^; ve' v) was a' sc dcses. n?s c„ a me '-a' md-ess^;m, as was -ct ' was blocked, a:

* C/- * nv £2' t-e tetnat exhibited ant'-KIV activity, in addit'cn. ov divid'nc the MTO bv tne 11 bad ORIGINAL

	AP 0 0 0 2 3 3
a tne-ace-t	ic ^;nde* was obtaired. Ze^er* v. t^he f'e^aoe-tic index is a
~easure :	- 2 q - - - - e a ^c' a a e a e s a' ~ a. ·. a- e a r^; c - t - e- a t^c-1 ^;e ' r e e χ s

	Figure 1 eexdnsfates tne a-f'--lv a:t’.'t_, e* eae.n :·' tne ;e- ,12
~ l s 3 a':	: t^c at s e1 a t - ...; t-'^c, t-° e- t-e am ¹ $ -----
C.nEs -a-get	—’ 2.15^1 te , *-··- t-e ::,, -a-ged '-ex 2.23ul te
ine :.:. 'S’	ares? sane ten -arced ~-z~' 22 te 1'2. ~nese va’ues a-e a’’
presentee	at . e ... be.ow. TABLE III

CHE	KTDGD Ant i-HTLV-I I IB Activity iDc-KB LuL· -- ,-\ . - * C * 7 3 3 3 --^: . . «Ζ . J -·
>fz	-3 w.*- _.GZ 7 3..·-
• o * T L. -	-2 1.32 2.30 22.22
*32	22 2.26 2.70 76.92
#32	22 0.45 0.66 44.44
#35	22 0.4 2 1.70 24.39 _
#35	-- -. — —' — . ο υ 3 v, „ >-
#42	22 2.34 2.⁷2 53.32
eZZ	42 2.22 2.65 2”.51
C

	using a similar xeted. tne 2-Es «e”e tne- tested agamst seve- 1
clinical ^Sse'	iates '2, AP, L. 2. ³, C. '} a-d two (2' add't'tnal HIV 'abc-ate-/
⁴solates. 't;	1 and HIV2;, in noma' stir.uiated P3^vNs. (’He el inical ’Isolates.
A * ^r & ^:	ite-ate-y 'solate, -as tee- ettai-es --ex 412S eatients t-eatec at
Oedars-Sira'	Vedica' Center, in _es Ance'es, Oa'.'te-nia. The HIV-2 (_AV-2°22'i BAD ORIGINAL
¹ tJ- - - ³

AP 0 0 0 2 3 3 nad bee” obtained ‘'tt Luo Mcntac”7 e-. at the :st'tute ^pasteu-, ·η .bus -i ex”·, ft a”f• ' r ” ~ j ’ S * 3 * ° S ’ j 1' * w' ί Γ V 3 ^r * ' 2 6 * ‘

15) 2-Es ex”ioited att'v't/ aoa^;”St f vt_? ata'”st -os: :* 'v. ·η Figure 2. a” te' • ¹ so1 ates, wr.e-ea; f' , two (2) o^r tne te.” ; 12) C.HEs (?~L a”d «49), ir Figure 3. snowed a: inhibitor·/ aooiv't·. aca'nst tre -)V2 'so'ate. '”e ”~:/ts o^; tri;

<-* ' c ~ ’c c or· *, r a »·♦ · *·j _t g»* .· ·/ a ς

As i'' wstnateo in Figure 4, 2-2 exn'fteo g-eate- t”i innibi tier, fo- six 16) of the seven f'· ””'tary H17-1 isolates. w't' -anginc '”or 3.20i/ tc 2.5;/.

” Figure 5. 2-2 «2 λ;* *o_”t t: ”a<e et-a‘ 0” feate- :

* Z ”** * Γ Ξ 2 τ'» θ’· S 3 ** · '22 7- 2 *2 2 . *» * 2 d * ** ?.^Λ 2 *

-s i/_tt-ated Figure 6. ChZ #21 'o- a cf o”e ^; 1) of tne seve.” 17'

--a”,· .'” Figure 7. 2-2 «22 ex”'f'tec g-eate- t”a 927 active (5) o' tne seven (7) primary ^so'ates, with an 12_9c 0.52.

Figure 8 illustrates tne neutralization activity ^ror the graph illustrates, CHE #32 exhibited I0₉₀ activity against 7' seven (7) orirrary isolates, with an 12,. ranging *·*οη 0.52«! to '

1” Figure 9, CHE «25 'nr'titec six (£' o* t-e se.·:· isolates. witn an )2-. rangi-g ‘-or C.S.2u7 to 3.2/.

-s 'I'ustrated Figure 10. o”7 v tnown w-7ve 15) of ates we-e 'rhio^;ted more tnan 927 t

As * h β c-ι 4 * »· in in Figure 11. a” cut one (21 ra-v ' te were nan 9 _-u- oy 1 *41, w t n an be twee” 1..u« · to t. 2,21 ·.

2.-Ξ A'aa exhibited create” t-.an 927 irhio'fo” against ne six 16; p-'ma-y 'solates in Figure 12, w-t” an 12-. -arcing *” ”5. 25 ’6

BAD ORIGINAL

AP 0 0 0 2 3 3

In Figure 13, CHE *49 •eate- man 9Ch, w'tn an IC₀„ c~ se*. e' ates

D. Syncytial Inhibition λ n a »· a / rorrrat'.

sHc ^rea:

ceatn, ^-s a

-c-mamc- cepe.ncs cells pea-'ng the mt enact i.

were tre^e^cre De^r’*c’*'^wec to ceie^T^e w ΐ ΓΓ ' 4 *, ζ 1 2** c * ’ ' pc

2-3 -ac -ft c-'-c

Mo’t Ills and Η²ΒΑ-_ *e-e emclcye:

ce'*i s?ez' re'·'s , ^es^ezt^; v. 3e* oc^ros<^ e: ai . , 222:4⁷C-/ ' gc; ’ soloes

C'>

* , ..j - , 3. - u. 3’ eac r 3 ’ ire

CH£s were preincubated separately with e'tne- me 1-retted ^Mo't III2 uninfected HPBALL cells for a standard ti~e pe-'od. ~ne cells were several t^mes and the two cell types were nixed Cn cu'ture. ^Tne pesyncytial inhibition cf both methods was t-en evaluated ^fo- a CHEs microscopy eighteen (13; hours atte( \ ~ st tne men was·

Γ oo £ 'sts :~e o^e aot’v'tv e'3'3'ted 3/ eaor

BAD ORIGINAL

i. C“3 ^’1 -nl'C?

AP 0 0 0 2 3 3 TABLE IV-' ’32 IHO'32’22 232.2 --5-4,,'

#1 #8 #21 #39 #32 #35 #39 #41 #44 #49 rsT4

90.2 93.1 3.7 ⁷ 5.9 93.6 95.1 5 ’.9 ”. 4 33.9 35.1 32.

° 2 9 52'	' 4 . ' = 2.0 15.1 '3.5 ^{7 7} 5 523 ⁷ - ^c 1^: '
v.J-i - 22. .2 -3.x w- 2~Z . Z	3'. 55.5 2 15.9 15.5 51.9 2 (2.2.'
2 7 ,., Λ “ 2 2 7 T ^{1 1} 7 2 #1 «3 «21 #30	λ i *1 ^r ^ · ~ -· - ” ' ^1,4 ~ ^x «32 «35 #39 «41 #44 #49 rsT4
c . __.o .6 4 7.2	'5.5 25.4 29.5 52.5 52.5 '2.5 52.5 (2«' <
1Z 2 25.4 13.2 39.5 '	3\ 2 22.5 15.9 5 1.9 55.' 4'.2 52.2 . '
2.3«' 2 9.4 3 16.9	'39 ' 155 434 4 ⁷2' ⁷ 5 - ( 2 5''

5-'e*'.<, as tac.'ated abc/e Sect'tn 4 = s'~ i;, (c; ;·' the ter (10) CH3s (#1, #S. #32 and #35) exnioited create” tr.ar 90% inhibition syncytia formation when the CH* was preincubated w'th the uninfected cel's. However, only one (1) (#44) exhibited greater tnan 90% irh'bition of syncytia

formation wⁿen ire 2H3 was pr;	r.ncubated w'tr, tne infected cel's.
Ar acc't^;cra' exps	<.nent was tne--’·''.?' ce-*cr~ec tc decp-nr--
-retrer th’s arti-HlV activity	,- c'ccuc5d P v tne 2-3s ccc-r’-ed ' ~s^; ce t^np c^ρ'^c
’ Γ ζ ^r ' C ζ^Λ·£ C 7 ' S	»5-e 'r-ecte: one 11; -.our before adding tne 2H3s.
-c.' --p ^pvo·^ ,= ς 4 :	e 'nnib'tcr, 42’. as a zz~z~z'. In Figure 14,
13«' of 2-3 «32 exn-pited 1337	τibt*or 3- HIT ro^'icat'or tne ζ~'r·ectes
cells wit” octn ccses cf H’lV-	•2133 '52 ’2I2_C- arc 122 ’2I2_c-(. ’?^;s ’•es/t
appears to indicate that the :	.tservec _v ^;:-p *~ΐ'--ΐν atfvit. rav act^av

Tne -esdis tabu'ated above were obtained f”cr one ^z 1' series of experiments. These experiments have not yet pee” ^zzzz^z to verify the reproduced·'' ity of tne above results.

ng/2S'6

BAD ORIGINAL C s*

AP Ο Ο Ο 2 3 3 within the ce' , althoucn the poetise mechan'S'

E. End-Polnt-D1lution Cu 11 u r e<

/ tune method, as deso-ioed in the •c u.r.o-ne’· --ο --c ay ::: 152:-152:

; η θ g r. - . Γ Λ ’ η ζ - .H ’ lidenature, was use: to :ete^r in crroo’cally infested 33/1113 se'ls. is indicated in Figure 15, 1«^? of C'-ίΞ #21 produced no vi-a' t'te- cr.ance. a¹, tnoucn 12«! of 2.-2 #21 crocuses a 12 fold cec-ease .-'ra' s^;se-. ^Ms* _/ u t e s _ ; 16 j in d _. _ r ο i ΰ '^e.nce, ;^ese resu':: 'j·*? pre-''ess'on studies 'n Figure 14. ''s^re se'/s we-e in'ested ore ’’ou” be^p-e asSid s-e 2n2s;. we-ε ^; t aosea-es fas s*e r:^;~T, ass'v's_. o' Sf 2-2: a:sua'‘y :::,.- s-e oe'‘ '-te-ior. roweve-, as fc'oated aoove, f= precise mechanism fo- the 2H2 activities is sti'1 under ·nvestiaation.

e*corr*,np»·

F. Reverse Transcriptase Assay

The HIV 221-3 3' ensyme «as 's: of eaor 2H2. using a v-.own reve-se fans:et al . , Off 225:^51--453 Ί?-!’.;

re: wtn varyfg ano-'::

oioo-e'-ioa' assay, -o

1.93, .

uoes'f ca y, v'rus pa-t's.es we-e p-es'P'tate:

supe-natant as follows: 2.2 volume; oclyetny'ene s'yoo’ (la-bcwar 5222 ' were asses :

ou'oure ^r’u'ds and s-e susoe-s^;on was places c- 'se pvewas ce.ofifuced at 22 22 -ev/m'4M sodium on'o-’se and 2.6 ml cf 222 fweh * Γ:

of harvested 'ne suscens·.

? C ' D ί d ί 6 a t S resuspended in 3Q0«l of 50« (’ey volume! glvserol i05mM tris-hll, pH

BAD ORIGINAL

AP Ο Ο Ο 2 3 3

C-tt'Othre' tai . 150rr.M potass'un tr	<C”'ce 0.025% ^Y<35'. V'rjs
ta-tit'et «e-e O'.smteO o ,· adc't'	' 2 * 2 * 2 2 0 90 * ””' ” 2^r ~ ' > *·'

totass6- c-'o-'ce sclu’/on.

' r p go , - Γ ^r S5 J £ 0 '	:-;e-t-at5 --or a :o :_-e o* 6Ό 66Ξ »a;
ave-ed c~ a 20 to 50% 6 λ°-·οηι'	: soo-ose t-ad'g-t -- 6-^ t'^;s-T 6“ 6‘
ggrta'ci-o 61M soo6r o6;-6e a'	'2 1 ‘ A dⁿ'^ ~ v ^c ' 2 Γ * d * * ~ ~ ‘
'-aotn-s t' 0. -' Ag-e	:66:::: -'-or tn 0:::0- o^£ tte o-ad6-t a- :
66 oort‘'o's, '” a ‘^;oa' .:6-:- ;	/ 66’ ::--.0----0 o;-·· :-6--6 i-r ·-·'
c’tr'othre'ta' , tctat:6~	o-^;:e a-o oS^o -- :e-:6:e - o-6g- pc’y ^f'~'^! .
-- arc ~o'y '6 · r h . -_c- -’ : 2 - ·s -- - - : - · s --	Λ-t- :;-^M 6²6 ο- 56' 6 oo'y 6 — · o'.,..,

d'22 22~22'~ed 15-^M r 26 222-22^	'226 22 6 6 2 2 6 2 X ’» ' 2 I ^r - 2 ' 6 2 2 ’ 2
2*' p ^222262-2, ' f!5· 0' '222	. . - . --, - ^Λ ,⁷ 6 ’ - - ' ” 2 . X . w ' 2 6 2 2 2 6 ~ ~ ~ *
:L2 6 ~:6 . 6g a.rcurt ea;-	O'^ML 262 62 Sd”v 22 '*2^r'2''2 520 22d 900 C 226
«2; ~~ activity '2 ^622^2^2	;r Odo'e < 26'z* arc Figure 16. As
'' '2S2”d262 . 2^6 **62 2' 22 '2'2626	---- - - -- - «- 6 Z - ,ι γ “ 06

	TABLE V
CHE	Anti-HTLV-IIIB RT Activity ' iD₅^an io^Ldj
	2 ’ > .
• 0 S ’	-i — i— — A

ff 2

r 22	6 6 5.6
x 2	o . 5 2 >6.6
*29	--- - r\
c 2 '	• - - 5.6 o ;>

«29

< . / · C ‘ u

BAD ORIGINAL

AP Ο Ο Ο 2 3 3

G. Ex Vivo Experiments Utilizing CHEs #32 And #49. The Best Mode CHEs ravfg oetermfed ire’ a^r t · fte-fe-ts cdncudtea in :

•esent'es as diesel',’ as tossf tc fovoe an erne·—enta.- mode iⁿai ³··-£, 3':6E'4-65?3 {1392). Eo” tnese exteriments, S'-Es «22 and *49 were -i'''?ea. as t.nev we-e ccnsⁱ'de**ed ine leaded cancldates arcrc ie ten (121 2H1 a-f--1; activity. These t*c )2) :2-/:/2- (C-£s) wee selectee cased zz: tne exte-'mensa' data ta date. However, f's se'etf on z^r CHEs «22 and #49 as ine oest node CHEs is net meant tt 'orec'ose come tsss·t ·' i ti es, as fttfe as he:

- as~a ana iM.Ss we-e attained : Γ c : 3. 2 ' -2 2 w'' - n ; J Z ί nt. An eva-td⁷nt-di'utian v .2-/ saf f f -1,-1 ' t free O' ////. a-a derated safer: w · t n A. A 2 ; a - a H ‘ a r a

-et.ncd as cescrised aaave, was

Di.

ar e-ts: a:en. In the HlV

Figure 17, the HIV tite-s in AB.HNs are i 11 as fated on the toe gnat’ titers in plasma are illustrated on the Dcttcm graph.

se a<*^>

.rqi	HIV-1 was recovered	from the -r · n ’' r& V. - J ί k J	?3MNs cel's.	of al 1 and a	three * e 3 r t'
ng from	12 to 1.2C0
.'/er	’ ⁷ - r . ti 1 i	CHE «32 was	n:	v,eve,	H 17 -1	was de
, rr·	1 », + ~ *	20 *213/12⁶	* c' ’ ς a		-i H £ r* ,	ρ a s ρ ’ n

	«22 was	added, v'fal	1 tite-s ·	- £' ’	: 3.2e r	ts we-e
- 5’	's. '-'ea	«-’.ρ. ine	t d t a' -1	-1 f :	Θ s ^;:	o'asna

'. e a e a s e d «i a 1 f . t e * s :: I .

~s ' .seated Figure 18. τ -Ξ*·“ »-9 Hlΐ t'fs defeased --O'- a -pa- ft»·· r cel's. 7ne addition of 1Z of CHE «49 ^ffthe ^r win ;ed the viral f'ter to 2.51

BAD ORIGINAL

AP Ο Ο Ο 2 3 3 asma, hcwev?tcse c ^25 aseveact' ·.^; x ^r i t^; ’nese experiments av t^re res-'fin<_ £ -- i ·v~ .-- c *n»· nn * gr, * · ^ ' ' £ *“ * ' ~ * Γ'P** 3 y ' '*** £-*-<« »λ n r »

c. ten (1C) cf tne ·;ίι_.·-$-'χ (55) 2-Es testet .e'e tc e*<'p·

9teSet ant'--!7 activity yy v ~ t c. -'ve '5) c^f tnece E-Es '«’1, »2. P a'sc Cempnstnatec s~csta-t^;a' sjt.-t'a' a;t'.-f_?.

·”) E-Es (#S, #2C. #22. #25. ap *49) ex/Dii?: i c^; ter·,· ty aca^;nst reve-se t-anscr·ptase. ^;r-a”y. CHEs ‘22 a-: «4? 57=- py v' v n ccse cep eno 9-1 a t' - n 1a p t' '·' t · ' n pa t' °·* p t'a s“a vc 0 - *·“

Claims

1. A method of inhibiting HIV in host cells infected with HIV by contacting said host cells in vitro with a pharmaceutical preparation comprising an extract

5 from Salvia miltiorrhiza, at a concentration of said extract which is effective to inhibit expression of HIV p24 antigen.

2. A method of inhibiting HI'.' in host cells infected HIV by contacting said host sells in vitro with a

10 pharmaceutical preparation comprising an extract from

Lonicera japonica, at a concentration of said extract which is effective to inhibit expression of HIV p24 antigen.

3. A method of inhibiting HIV in host cells infected with HIV by contacting said host cells in vitro

15 with a pharmaceutical preparation comprising an extract from Scutellaria baicaleusis, at a concentration of said extract which is effective to inhibit expression of HIV p24 antigen .

4. A method according to any one of claims 1 to 3

20 in which the preparation has a concentration of 1 gram of said extract per 1 milliliter of said pharmaceutical preparation, administered in an amount effective to inhibit expression of HIV p24 antigen.

5. A method according to claim 4, wherein said

25 extract is selected from the group consisting of an active component, a combination of active components, a biological

BAD ORIGINAL

AP 0 0 0 2 3 3

- 21 metabolite, a derivative thereof and a combination of the above .

6. Use of an extract from a Chinese herbal medicine, which extract exhibits anti-HIV activity by inhibiting syncytia formation and reverse transcriptase activity, in the manufacture of a pharmaceutical preparation for use in the treatment of an HIV infection or

HIV related disease.

7. Use according to claim 6 in which the extract is from Salvia miltiorrhiza, and in which the preparation has a concentration of 1 gram of said extract per 1 milliliter of said pharmaceutical preparation.

8. Use according to claim 6 in which the extract is from Lonicera japonica, and in which the preparation has a concentration of 1 gram of said extract per 1 milliliter of said pharmaceutical preparation.

9. Use according to claim 6 in which the extract is from Scutellaria baicaleusis, and in which the preparation has a concentration of 1 gram of said extract per 1 milliliter of said pharmaceutical preparation.

10. Use according to claim 6 in which the pharmaceutical preparation comprises an extract of Coptis chir.eusis, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

BAD ORIGINAL

- 22

11. Use according to claim 6 in which the pharmaceutical preparation comprises an extract of Ligusticum wallichii, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

12. Use according to claim 6 in which the pharmaceutical preparation comprises an extract of Illiciun lanceolatum, or a an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

13. Use according to claim 6 in which the pharmaceutical preparation comprises an extract of Isatis tinctoria, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

14. Use according to claim 6 in which the pharmaceutical preparation comprises an extract of Salvia miltiorrhiza, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

15. Use according to claim 6 in which the pharmaceutical preparation comprises an extract of Srycibe obtusifolia , or an active component, a combination of bad ORIGINAL

AP 0 0 0 2 3 3

- 23 active components, a biological metabolite, a derivative of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

16. Use according to claim 6 in which the pharmaceutical preparation comprises an extract of Acanthopanax graciliatylus, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

17. Use according to claim 6 in which the pharmaceutical preparation comprises an extract of Bostaurus dcmesticus, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

18. Use according to claim 6 in which the pharmaceutical preparation comprises an extract of Inula helenium, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

19. Use according to claim 6 in which the pharmaceutical preparation comprises an extract of Lonicera japcnica, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

SAD ORIGINAL

AP Ο Ο Ο 2 3 3

- 24

20. Use according to claim 6 in which the pharmaceutical preparation comprises an extract cf Polygonum bistorta, or an active component, a combination of active components, a biological metabolite, a derivative

5 of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

21. Use according to claim 6 in which the pharmaceutical preparation comprises an extract of Scutellaria baicaleusis, or an active component, a

10 combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof, capable of inhibiting the expression of HIV p24 antigen.

22. Use according to any one of claims 6 to 21 wherein said pharmaceutical preparation comprises an

15 acceptable excipient.

23. Use according to any one of claims 6 to 22 wherein said pharmaceutical preparation is suitable for administration parenterally.

24. Use according to any one of claims 6 to 22 20 wherein said pharmaceutical preparation is suitable for administration intravenously.

25. Use according to any one of claims 6 to 22 wherein said pharmaceutical preparation is suitable for administration intramuscularly.

25

26. Use according to any one of claims 6 to 22 wherein said pharmaceutical preparation is suitable for administration intraperitoneally.

BAD ORIGINAL A

AP 0 0 0 2 3 3

- 25

27. Use according to any one of claims 6 to 22 wherein said pharmaceutical preparation is suitable for administration subcutaneously.

28. Use according to any one of claims 6 to 22 wherein said pharmaceutical preparation is suitable for administration enterally.

29. Use according to any one of claims 6 to 22 wherein said pharmaceutical preparation is suitable for administration orally.

30. Use according to any one of claims 6 to 22 wherein said pharmaceutical preparation is suitable for administration rectally.

31. Use according to any one of claims 6 to 30 wherein said pharmaceutical preparation is in combination with a supplemental antiviral agent, an immune modulator, a chemotherapeutic agent, an antibody, or a combination thereof.

32. A composition suitable for injection for preventing or treating an HIV infection or HIV-related disease in a host, comprising a medium containing an effective amount of an extract of a Chinese Herbal Medicine having anti-HIV activity in admixture with a pharmaceutically acceptable excipient.

33. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract of Coptis chineusis, or an active component, a combination

BAD ORIGINAL

AP 0 0 0 2 3 3

- 26 of active components, a biological metabolite, a derivative of said extract or a combination thereof.

34. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract of Ligusticum vallichii, or an active component, a combination of active components, a biological metabolite, a derivative of said extract or a combination thereof.

35. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract of Illicium lanceclatum, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof.

36. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract of Isatis tinctoria, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof.

37. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract of Salvia miltiorrkiza, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof.

33. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract of Erycibe obtusifolia, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof.

BAD ORIGINAL

AP Ο Ο Ο 2 3 3

- 27 39. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract of Acanthopanax graciliatylus, or an active component, a combination of active components, a biological metabciite, a derivative of said extract, or a combination thereof.

40. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract of Sostaurus dcmesticus, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof.

41. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract cf Inula helenium, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof.

42. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract of Lonicera japonica, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof.

43. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract of Polygonum bistorta, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof.

BAD ORIGINAL

AP000233

- 23

44. The composition of claim 32, wherein said herbal extract comprises an effective amount of an extract of Scutellaria baicaleusis, or an active component, a combination of active components, a biological metabolite, a derivative of said extract, or a combination thereof.

45. An assay method for the detection of an HIVrelated infection in a host, which comprises the steps of:

contacting a test sample from a host suspected of infection with HIV with an extract from a Chinese Herbal Medicine which exhibits anti-HIV activity by inhibiting syncytia formation and reverse transcriptase activity, the extract being used alone or conjugated to a label; and determining the presence of HIV in the sample.

46. The assay method of claim 45, wherein the test sample is selected from the group consisting of whole blood, lymphatic fluid, serum, plasma, semen, saliva and cerebral spinal fluid.

47. In the assay method of claim 45 or 46 in which said extract is from Coptis chineusis, Ligusticum wallichii, Illicium lanceolatum, Isatis tinctoria, Salvia miltiorrhiza, Erycibe obtusifolia, Acanthopanax graciliatvlus, Bostaurus domesticus, Inula helenium, Lcnicera japcnica, Polygonum bistorta or Scutellaria baicaleusis.

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- 29 48. The assay method of any one of claims 45 to 47 wherein said extract is further selected from the group consisting of an active component, a combination of active components, a biological metabolite, a derivative thereof,

5 an anti-idiotype antibody of said extract and a combination thereof.