OA17066A - Anti-viral properties of aloe vera and Aquired Immune Deficiency Syndrome (AIDS) treatment. - Google Patents

Anti-viral properties of aloe vera and Aquired Immune Deficiency Syndrome (AIDS) treatment. Download PDF

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Publication number
OA17066A
OA17066A OA1201300027 OA17066A OA 17066 A OA17066 A OA 17066A OA 1201300027 OA1201300027 OA 1201300027 OA 17066 A OA17066 A OA 17066A
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Prior art keywords
aloe
acid
composition
aids
dihydroxy
Prior art date
Application number
OA1201300027
Inventor
Ivan E. Danhof
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North Texas Medical Associates
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Abstract

A pharmaceutical composition comprising a combination of formulations derived from aloe vera for the treatment of Acquired Immune Deficiency Syndrome (AIDS) or HIV infection is described herein. The composition comprises: (i) an injectable sterile polymannan extract, (ii) Raidox (aloe anthraquinones and their diacetyl derivatives), and (iii) a freeze dried aloe vera powder, aloe vera juice, aloe gel or a combination. In addition one or more nutritional supplements comprising fatty acids, proteins, minerals and metals, vitamins, salts, amino acids, and other pharmaceutically acceptable excipients may also be include to counteract the chronic diarrhea, digestive upsets, and weight loss seen in some patients before and during the treatment course. A method for treating the AIDS or HIV infection using the composition of the present invention is also disclosed.

Description

Technical Field of the Invention
The présent invention relates in general to the field of Acquired Immune Deficiency Syndrome 5 (AIDS) treatment, and more particularly, to compositions and uses of aloe vera, related products, and dérivatives for the treatment of AIDS.
Background Art
Without limiting the scope of the invention, its background is described in connection with anti-viral properties of aloe vera and related compounds and therapeutic uses of the same.
U.S. Patent No. 7,169,414 issued to Shupe and Coats (2007) describes antimicrobial agents and method for isolation thereof from the gel liquid of Aloe vera includes at least one antimicrobial agent isolated from the clear gel isolated from the whole leaf of the Aloe vera plant, wherein the antimicrobial agent is an agent produced by the Aloe vera and/or indigenous bacteria that colonize the Aloe vera plant, is disclosed.
WIPO Patent No. WO/1993/008810 issued to Mcanallcy et al. (1993) discloses the use of Accmannan in treating a number of conditions where the principal mechanism of resolution or cure requires intervention by the patient's immune System. Acemannan has direct stimulatoiy effects on the immune System. Methods for treating cancer, viral diseases, respiratory and immune regulatory diseases, inflammations, infections and infestations by administering an acetylated mannan 20 dérivative, such as acemannan derived from aloe, are described. The method finds use in tissue cultures, animais and plants.
Disclosure of the Invention .
*
The présent invention is a composition and method of treatment for acquired immune deficiency syndrome (AIDS), The composition disclosed herein comprises a combination of polymannan 25 extract (PME), anthraquinones, and freeze dried aloe powder along with one or more nutritional suppléments for the treatment of AIDS.
One embodiment of the instant invention disclosés a pharmaceutical composition for treating, amelioration of symptoms or both of an Acquired Immune Deficiency Syndrome (AIDS) or a HIV infection in a subject comprising: a stérile injectable polymannan extract formulation comprising one 30 or more aloe polysaccharides, wherein the aloe polysaccharides comprise one or more small chain, medium chain, large chain, vciy-large chain polysaccharides, or any combinations thereof, a formulation comprising one or more aloe anthraquinones, diacetyl anthraquinone dérivatives, and combinations and modifications thereof, a formulation comprising a freeze dried aloe powder, an aloe juïce, an aloe gel or a combination wherein the powdet is administered as is or after reconstitution in a suitable liquid, and a formulation comprising one or more optional nutritional suppléments selected from the group consisting of fatty acids, proteins, minerais and mctals, vitamins, salis, amino acids, and other pharmaceutically acceptable excipients. In one aspect of the instant invention the polymannan extract is administered intravcnously, intramuscularly, 5 subcutaneously, intraperitoneally or by any other suitable parentéral route. In a spécifie aspect the polymannan extract is administered intravenously at a dose of 10-15 mg three times a week. In a related aspect the formulations other than the polymannan extract are administered orally. In another aspect the one or more aloe polysaccharides in the polymannan extract hâve molecular weights ranging from 50,000-10,000,000 Daltons.
The one or more aloe anthraquinones used in the composition of the présent invention are selected from the group consisting of Aloe-emodin, l,8-Dihydroxy-3-(hydroxymethyl-9,10-anthracenedione,
1.8- Dihydroxy-3-(hydroxymethyl)anthraquinone, 3-Hydroxymethylchiysazin, Aloe-EmodineAnthrenol, Aloinosîde-A, Aloinoside-B, Aloin-A, 10-Glucopyranosyl-l,S-dihydroxy-3(hy droxy methy 1)-9( 10)-anthraecne, 1,8-Dihy droxy-3 -hy droxymethyl-10-{6-hy droxymethyl)-3,4,5- trihydroxy-2-pyranosyl, anthrone, 10-fr,5'-anhydroglucosyl)-aloe-emodm-9-anthrone, Barbaloin, Aloin-B Epimere of Aloin-A, Isobarbaloin„ Aloinoslde-A, Aloinoside-B, Anthranols, Anthraquinone-glycocide, Chrysaminic Acid, Chrysophanic Acid, ChrysoDhanol, Chrysophanolglycoside, 1,8-Dihydroxyanthraccne, Emodin, l,3,8-Trihydroxy-6-methy1-9,10-anthracene-dione,
1.3.8- Trihydroxy-6-methylanthraquinone, 4,5,7-Trihydroxy-2-methylanthraquinone, Frangula emodin, Homonataloîn, Hydroxymethylanthraquinone, Rhein, 9,10-4,5-Dihydroxy-9,10-dioxo-2anthracene-carboxylic acid, 1,5 -Dihy droxy anthraquinonc-3-carboxylic acid, 4,5Dihydroxyanthraquanone-2-carboxylic acid, Chrysazin-3-carboxylic acid,
Trihydroxymethylanthraquinone, and modifications and dérivatives thereof.
In another aspect the aloe anthraquinones are administered at a dose ranging from 50-75 mg/day. In yet another aspect the freeze dried aloe powder, the aloe juice, the aloe gel or the combination is administered at a dose of 400 mg one or more times a day. In one aspect the aloe juice comprises of about 2% total solids. In another aspect aloe juice comprises glucomannan polysaccharides. In a spécifie aspect the glucomannan polysaccharides hâve molecular weights ranging from 50,00010,000,000 Daltons. In yet another aspect wherein the one or more fatty acids are selected from the «
group consisting of Linoleic Acid (LA), Gamma Linoleic Acid (GLA), Eicosapcntaneoic Acid (EPA), Docosapentaneoic Acid (DPA), Docosahexaenoic Acid (DHA), and D-alpha-tocopherol. The composition as described hereinabove releases one or more cytocommunicators selected from the group consisting of TNF-a, IL-Ιβ, IL-2, IL-6, and INF-γ, wherein the release stimulâtes the growth and cytolytic action of one or more Naturel Kîller (NK) cells in the subject
In another aspect the présent invention provides a method of treating, ameliorating symptoms or both of an Acquired Immune Deficiency Syndrome (AIDS) or a HIV infection in a subject comprising the steps of: idcntifying the subject in need of the treatment or amelioration of the symptoms against the
I
AIDS or the HIV infection and administering a thcrapcutically effective amount of a pharmaceutical composition sufficient to treat or amelioratc the symptoms of the AIDS or the HIV infection.
The pharmaceutical composition used in the method of the présent invention comprises the following:
(i) a stérile injectable polymannan extract formulation comprising one or more aloe polysaccharides, t
wherein the aloe polysaccharides comprise one or more small chain, medium chain, large chain, very-large chain polysaccharides, or any combinations thereof, (ii) a formulation comprising one or more aloe anthraquinones, diaeetyl anthraquinone dérivatives, and comhinations and modifications thereof, (iii) a formulation comprising a freeze dried aloe powder, an aloe juice, an aloe gel or a combination wherein the powder is administered as is or after reconstitution in a suitable liquid, and (iv) a formulation comprising one or more optional nutritional suppléments selected from the group consisting of fatty acids, proteins, minerais and metals, vitamins, salts, amino acids, and other phannaceutically acceptahle excipients.
In one aspect the polymannan extract is administered intravenously. The dosage of the injected polymannan extract is 10-15 mg three times a week. The aloe anthraquinones the freeze dried aloe powder and the optional nutritional suppléments are administered orally. The one or more aloe anthraquinones used herein are selected from the group consisting of Aloe-emodin, l,8-Dihydroxy-3(hydroxymethyl-9,10-anthracenedione, l,8-Dihydroxy-3-(hydrDxymethyl)anthraquinone, 320 Hydroxymethylchrysazin, Aloe-Emodine-Anthranol, Aloinoside-A, Aloinoside-B, Aloîn-A, 10Glucopyranosyl-l,S-dihydroxy-3-(hydroxymethy 1)-9( I O)-anthracene, l,8-Dihydroxy-3hydroxymethyl-10-(6-hydroxymethyl)-3,4,5-trihydroxy-2-pyianosyl, anthrone, 10-{l’,5'anhydroglucosyl>«loe-emodin-9-anthrone, Baibaloîn, AIoin-B Epimere of Aloin-A, Isobarbaloin„ Aloinoslde-A, Aloinoside-B, Anthranols, Anthraquinone-glycocide, Chiysaminie Acid,
Chiysophanic Acid, ChrysoDhanol, Chrysophanol-glycoside, 1,8-Dihydroxyanthracene, Emodin,
13.8-Trihydroxy-6-methy 1-9,1O-anthracene-dione, 1,3,8-Trihydroxy-6-methy lanthraquinone, 4,5,7Trihydroxy-2-methylanthraquinone, Frangula emodin, Homonataloin,
Hydroxymethylanthraquinone, Rhein, 9,10-4,5-Dihydroxy-9,I0-dioxo-2-anthracene-cajboxylic acid, l,5-Dihydroxyanthraquinone-3-carboxylic acid, 4,5-Dihydroxyanthraquanone-2-carboxylic acid,
Chrysazin-3-carboxylic acid, Trihydroxymcthy lanthraquinone, and modifications and dérivatives thereof. In a spécifie aspect the aloe anthraquinones are administered at a dose ranging from 50-75 mg/day. In another aspect the aloe juice comprises glucomannan polysaccharides. In yet another aspect the freeze dried aloe powder, the aloe juice, the aloe gel or the combination is administered at a dose of400 mg one or more times a day.
The one or more fatty acids in the nutritional suppléments are selected from the group consisting of Linoleic Acid (LA), Gamma Linoleic Acid (GLA), Eicosapentaneoic Acid (EPA), Docosapentaneoic «
Acid (DPA), Docosahcxacnoic CAid (DHA), and D-alpha-tocopherol. In another aspect the composition rclcases one or more cytocommunicators selected from the group consisting of TNF-a, IL-Ιβ, IL-2, IL-6, and INF-γ, wherein the release stimulâtes the growth and cytolytie action of one or more Naturel Killer (NK) cells in the subject.
Yet another embodiment of the instant invention discloses a pharmaceuticai composition for treating, amelioration of symptôme or both of an Acquired Immune Deficiency Syndrome (AIDS) or a HIV infection in a subject comprising: a stérile injectable polymannan extract formulation comprising one or more aloc polysaccharides, wherein the aloe polysaccharides comprise one or more small chain, medium chain, large chain, very-large chain polysaccharides, or any combinations thereof, a 10 formulation comprising one or more aloe anthraquinones, diacctyl anthraquinone dérivatives, and combinations and modifications thereof, a formulation comprising a fteeze dried aloe powder, an aloe juice, an aloe gel or a combination wherein the powder is administered as is or after reconstitution in a suitahle liquid and a formulation of a nutritional supplément comprising:
Linoleic Add (LA) 280 mg
Gamma Lïnolanc Add (GLA) 80 mg
Eicosapentaenoic Acid (EFA) 45 mg
Doscosapatomoic Add (DPA) 9mg
Docosahcxacnoic Acid (DHA) 30 mg
tralpha'tocopbCTol 15 mg
In one aspect the polymannan cxtract is administered intravenously, whercas the formulations other than the polymannan extract arc administered orally. In another aspect the one or more aloe anthraquinones are selected from the group consisting of Aloe-cmodin, I,8-Dihydroxy-3(hydroxymethyl-9,10-anthracenedione, I,8-Dihydroxy-3-(hydroxymethyl)anthraquinonc, 3Hydroxymethylchrysazin, Aloe-Emodine-Anthranol, Aloinoside-A, Aloinoside-B, Aloin-A, 1020 Glucopyranosyl-l.S-dihydroxy-S-fhydroxymethylJ-ÇOOJ-anthracene, l,8-Dihydroxy-3hydroxymethyl- 10-(6-hydroxymethy 1)-3,4,5-trihydroxy-2-pyranosyl, anthrone, 10-{l*,5'anhydroglucosyl)-aloe-emodin-9-anthrone, Barbaloin, Aloin-B Epimere of Aloin-A, Isobarbaloin,, Aloinosldc-A, Aloinoside-B, Anthranols, Anthraquinone-glycocidc, Chrysaminic Acid, Chrysophanic Acid, ChrysoDhanol, Chrysophanol-glycoside, 1,8-Dihydroxyanthracene, Emodin, 25 l,3,8-Trihydroxy-6-methyl-9,10-anthracenc-dione, l,3,8-Trihydroxy-6-methylanthraquinonc, 4,5,7Trihydroxy-2-methylanthraquînone, Frangula emodin, Homonataloin,
Hydroxymethylanthraquinone, Rhcin, 9,10-4,5-Dihydroxy-9,10-dioxo-2-anthracene-caiboxylic acid, l,5-Dihydroxyanthraquinone-3-carboxylic acid, 4,5-Dihydroxyanthraquanone-2-cart>oxylic acid, Chrysazin-3-carboxylic acid, Trihydroxymethylanthraquinone, and modifications and dérivatives 30 thereof. In yet another aspect the aloe juice comprises glucomannan polysaccharides.
I
A method of treating, ameliorating symptoms or both of an Acquired Immune Deficiency Syndrome (AIDS) or a HTV infection in a subject is described in an embodiment of the présent invention, wherein the method comprises the steps of: identifying the subject in need of the treatment or amelioration of the symptoms against the AIDS or the HIV infection and administering a 5 therapeutically effective amount of a pharmaceutical composition sufficient to treat or ameliorate the symptoms of the AIDS or the HIV infection, wherein the pharmaceutical composition comprises: (i) a stérile injectable polymannan extract formulation comprising one or more aloe polysaccharides, wherein the aloe polysaccharides comprise one or more small chain, medium chain, large chain, veiy-large chain polysaccharides, or any combinations thereof, (ii) a formulation comprising one or 10 more aloe anthraquinones, diacetyl anthraquinone dérivatives, and combinations and modifications thereof, (iii) a formulation comprising a freeze dried aloe powder, an aloe juice, an aloe gel or a combination wherein the powder is administered as is or after reconstitution in a suitable liquid, and (iv) a formulation of a nutritional supplément comprising:
Linoleic Add (LA) 280 mg
Gamma Linokmc Acid (GLA) KO mg
Eicosapentænok: Acid (EPA) 45 mg
Doscosapentaenoic Acid (DPA) 9mg
Docosahcxaenoic Acid (DHA) 30 mg
falphatoccpiianl ISmg
In one aspect the polymannan extract is administered intravenously at a dose of 10-15 mg three times a week and the other formulations are administered orally. In another aspect the aloe anthraquinones are administered at a dose ranging from 50-75 mg/day and the freeze dried aloe powder, the aloe juice, the aloe gel or the combination is administered at a dose of400 mg one or more times a day. In a related aspect the composition releases one or more cytocommunîcators selected from the group consisting of TNF-α, IL-13, IL-2, IL-6, and INF-γ, wherein the release stimulâtes the growth and cytolytic action of one or more Natural Killer (NK) cells in the subject
In another embodiment the pharmaceutical composition for treating, amelioration of symptoms or both of an Acquired Immune Deficiency Syndrome (AIDS) or a HIV infection in a subject «
comprising: a stérile injectable polymannan extract formulation comprising one or more aloe 25 polysaccharides, wherein the aloe polysaccharides comprise one or more small chain, medium chain, large chain, very-large chain polysaccharides, or any combinations thereof, a formulation comprising one or more aloe anthraquinones, diacetyl anthraquinone dérivatives, and combinations and modifications thereof, a formulation comprising a freeze dried aloe powder, an aloe juice, an aloe gel or a combination wherein the powder is administered as is or after reconstitution in a suitable liquid, 30 and a formulation of a nutritional supplément comprising:
NutrlUo··! lalbrrulio· per eerrlng
ScTvingStzo 48 g—™* Fat
Calodea 160 •Cholestérol
Protein 13 gmi Sodium
CarttohyAwtea 26 pn» Potassium
Parcaningee «f U.S. Raeommaadad Delly Allowucu
Protein Vitamin B
Vitamin A 70% Vitamin
VhwnfoC so% Folie Add
ThlamkM 50% Vitamin
Rjboflavin «o% Phosphores
NUcin 50% lodina
Cal dure 25%
Iroo so% Zinc
Vitamin D 30¼
gm 0 gm 120 mg eeotng
(U^S. RUA) pw «eniagt
30% Copper 50%
50¼ Biotm 50%
50¼ pantotbenic Add 50%
50% **Chromium 23 meg
20% * **Sdoiium 23 tncg
50% «Manganeae 2mg
30% **Ftbcr 3 gms
50% **Oetaco*ano1 2000 eneg
320 mg Prnlina - 1425 tag
«55 mg Sertna 700 me
lllSmg •••Tbreowina 510 tng
920 mg •••Tryptopban 145 me
310 mg Tyredne 630 mg
«00 mg «•Valine 755 mg
Ami·· Acida per 43 grue aerving
Alanine 373 me HhrddJnu
Ar^inina 450 mg Isoloudno
Aspartto add 830 mg ••*Xeudne
Cystine 65 mg •••Vysïne
Glutamle add 2640 mg •••Meddodne
Glycine 250 m* •••Phenyl alanine
Tnt.ietlleet»T Fiuctoee. Milk Solide, Celcran Sodium Cuelnato. Naturel and ArtUIclal flavora.
CeUuloae. Corn Bran, Potassium Chloride. Lecllhln, Maftodmtrùi. Curageenen. Wheat Oem Oil. (source ot i?, M^nuiien Oxide, Bcm Carotène, Selenlwn. Asoortotc Acid. Ferrous Fumante. d'Alpna
Tooophanl Acmm. Chromiura. Nüm-M. Aloe. Appie Pectln. Zinc Oxide. Mangeas* Sulfate, Vitamin A Paimrtxie, {^Calcium PantoOienatw Copper Sulftte. Pyridaùne Hydrocblcnde Riboflavin Thiamine Hydrochlorlde, Cobalatnin Coocaotnta, Vitamin Or Folio Add, Blotin and Potassium Chloride.
In one aspect the polymannan extract is administered intravenously and the formulations other than the polymannan extract are administered orally. In another aspect the one or more aloe anthraquinones are selected from the group consisting of Aloe-emodin, l,8-Dihydroxy-35 (hydroxymethyl-9,10-anthracenedione, l,8-Dihydroxy-3-(hydroxymethyl)anthraquinone, 3Hydroxymethylchrysazin, Aloe-Emodine-Anthranol, Aloinoside-A, Aloinoside-B, Aloin-A, 10Glucopyranosyl-1 ,S-dihydroxy-3 -(hy droxymethy 1)-9( 10)-anthracene, l,8-Dihydroxy-3hydroxymethyl-10-(6-hydroxymethyl)-3,4,5-trihydroxy-2-pyranosyl, anthrone, 10-{l*,5’anhydroglucosyl)-aloe-emodin-9-anthrone, Barbaloin, Aloin-B Epimere of Aloin-A, Isobarbaloin,, 10 Aloinoslde-A, Aloinoside-B, Anthranols, Anthraquinone-glycocide, Chrysaminic Acid,
Chrysophanic Acid, ChrysoDhanol, Chrysophanol-glycoside, 1,8-Dihydroxyanthracene, Emodin,
13,8-Trihydroxy-6-methyl-9,lO-anthracene-dione, 1,3,8-Trihydroxy-6-methylanthraqumone, 4,5,7Trihydroxy-2-methylanthraquinone, Frangula emodin, Homonataloin,
Hydroxymethylanthraquinone, Rhein, 9,10-4,5-Dihydroxy-9,l0-dioxo-2-anthracene-caiboxylic acid, 15 l,5-Dihydroxyanthraquinone-3-carboxylic acid, 4,5-Dihydroxyanthraquanone-2-carboxylic acid,
Chrysazin-3-carboxylic acid, Trihydroxymethylanthraquinone, and modifications and dérivatives thereof. In yet another aspect the aloe juice comprises glucomannan polysaccharides.
Another embodiment of the instant invention discloses a method of treating, ameliorating symptoms or both of an Acquired Immune Dcficiency Syndrome (AIDS) or a HTV infection in a subject 20 comprising the steps of: identifying the subject in need of the treatment or amelioration of the symptoms against the AIDS or the HIV infection and administering a therapeutically effective amount of a pharmaceutical composition sufficient to treat or ameliorate the symptoms of the AIDS or the HIV infection, wherein the pharmaceutical composition comprises: (a) a stérile injectable polymannan extract formulation comprising one or more aloe polysaccharides, wherein the aloe polysaccharides comprise one or more small chain, medium chain, large chain, vcry-large chain polysaccharides, or any combinations thereof, (b) a formulation comprising one or more aloe anthraquinones, diacetyl anthraquinone dérivatives, and combinations and modifications thereof, (c) a formulation comprising a freeze dried aloe powder, an aloe juice, an aloe gel or a combination 5 wherein the powder is administered as is or after reconstitution in a suitable liquid, and (d) a formulation of a nutritional supplément comprising: <
Natritional laformatioa per aerrtng
Serving Size 48 grains Fat 1 gm
Calories 160 •Cholestérol Ogm
Protein 13 gms Sodium 120 mg
Carbohydrates 26 gins Potassium 660 mg
Ptrceatagea of US. Recommended Dally Alkrrranca (U.S. RDA) per scrvtng:
Protein 30% Vitamîn E 50% Copper 50%
VitaminA 70% Vitamîn Be 50% Biotin 50%
VltaminC 50% Folie Add 50% PantotbenicAdd 50%
Thiamme 50% VïtaminBt2 50% ••Chromium 23mcg
Riboflavin 60% Phosphores 20% ••Selenitin 23mcg
Niacta 50% Iodine 50% ••Manganèse 2mg
Caldun 25% Magnésium 50% ••Fiber 3 gms
Iran 50% Zinc 50% ♦•Octaeosaiwt 2000 meg
Vitamîn D 50%
AmmaAdds per 48 gram aervtag
Alanine 375 mg Hlstidine 320 mg Praline · 1425 mg
Arginine 450 mg boleudne 655 mg Serine 700 mg
As partie add 850 mg •♦•Lcudno 1115 mg •••Threctrine 510 mg
Çystine 65 mg ♦••Lysine 920 mg ♦••Tiyptophan 145 mg
Glutamic add 2640 mg •••Méthionine 310 mg Tyrosine 630 mg
Glycine 250 mg •••Pbcnyîalaninc 600 mg •••Value 755 mg
IngraUeat» Fructose, Nonfit Milk Solids, Calcium Sodium Casdnme, Naniril and Artificiel flavors. Cellulose, Com Bran, Potassium Chloride, Lechhin. Maltodextrin, Canugeenan. «heu Gérai Oil, (source of Octacosaaol), Magnésium Oxide, Beta Carotène, Sélénium, Ascocblc Add, Ferrons Fumante, dAlpha Tocophanl Acetate, Chramiinn, Nlatfn. Aine. Apple Pectin, Zinc Oxide, Manganèse Sulfate, Vitamîn A PalmiaiE, d-Clldum Pantotbenate, Copper Sulfate, Pyridmdne Hydnxikxtde, Kiboflavin, Thunmne Hydroddoride, Cobtlamin Coocentrate, Vjtamin Folîc Acid·Βΐσΐ1η «w* Potassium Chloride.
In one aspect the polymannan extract is administered intravenously at a dose of 10-15 mg three times a week. In another aspect the formulations other than the polymannan extract are administered orally.
In yet another aspect the aloe anthraquinones are administered at a dose ranging from 50-75 tng/day and tfte freeze dried aloe powder, the aloe juice, the aloe gel or the combination is administered at a dose of 400 mg onc or more times a day. In one aspect the composition relcascs one or more cytocommunicators selected from the group consisting of TNF-o, IL-Ιβ, IL-2, IL-6, and INF-γ, wberein the release stimulâtes the growth and cytolytic action of one or more Natural Killer (NK) 15 cells in the subject.
Brief Description of the Drawings
None.
Description of the Invention
While the making and using of various embodiments of the présent invention are discussed in detail below, it should be appreciated that the présent invention provides many applicable inventive concepts that can be embodied in a wide variety of spécifie contexts. The spécifie embodiments 5 discussed herein are merely illustrative of spécifie ways to make and use the invention and do not delimil the scope of the invention. '
To facilitate the understanding of this invention, a number of terms are defined below. Terms defined herein hâve meanings as commonly understood by a person of ordinaiy skill in the areas relevant to the présent invention. Terms such as '‘a, '*an” and “the” are not intended to refer to only 10 a singular entity, but include the general class of which a spécifie example may be used for illustration. The terminology herein is used to describe spécifie embodiments of the invention, but their usage does not delimil the invention, except as outlined in the daims.
As used herein, the term “AIDS” refers to a status, as defined by the Center for Disease Control criteria. These criteria are any of the following two characteristics: 1. Infection with HIV and a CD4+ 15 cell count below 200/mm3 or a CD4+ cell count below 14%, with or without an opportunisme infection; or, 2. Infection with HIV and a CD4+ cell count greater than 200/mm 3 or CD+ eell count greater than 14% but who exhibil one or more of the following conditions: Candidiasis of bronchi, trachea or lungs, Candidiasis, esophageal, Cervical cancer, invasive, Coccidioid mycosis, disseminated or extrapulmonary , Cryptococcoses, extrapulmonary, Cryptosporidiosis, chronîc 20 intestinal (>1 month's duration). Cytomégalovirus disease (other than liver, spleen or nodes),
Cytomegalus retinitis (with loss of vision), Encephalopathy, HIV-related, Herpes simplex: chronîc ulcer(s) (>l month's duration) or bronchitis, pneumonitis, or esophagitis, Histoplasmosis, disseminated or extrapulmonary, Isosoporiasis, chronic intestinal (>1 month's duration), Kaposi's sarcoma, Lymphoma, immunoblaslic (or équivalent term) , Lymphoma, primary, or biain, MAIS 25 complex or M. kansasii, disseminated or extrapulmonary, M. tuberculosis, any site (pulmonary or extrapulmonary), Pneumocystis carinii pneumonia, Pneumonia, récurrent. Progressive multifocal leuko encephalopathy, Salmonella septicemia, récurrent, Toxoplasmosïs of brain, and Wasting syndrome due to HIV.
The term “aloe composition” as described in various embodiments of the instant invention refers to 30 any extract or processed form of a plant of genus aloe, family Liliaceae. For example, aloe extracts and processed forms of aloe for use with the invention may be obtained from aloe arbrorescens, aloe barbandensïs, or aloe ferox species of aloe. Any part of the plant may be processes or extracted, such as the leaf, stem or flower.
The term “pharmaceutically acceptable” is intended to include a carrier, a diluent or excipient that is 35 compatible with the other ingrédients of the formulation and not deleterious to the récipient thereof.
The ternis “administration of’ or “administering a” compound should be understood to ïndicate providing a compound of the invention to the individual in need of treatment in a form that can bc introduced into that individual’s body in a therapeutically useful form and therapeutically useful amount, including, but not limited to: oral dosage forms, such as tablets, capsules, syrups, 5 suspensions, and the like; injectable dosage forms, such as IV, IM, or IP, and the like; transdermal dosage forma, including créants, jellîes, powders, or patches; buccal dosage forms; inhalation powders, sprays, suspensions, and the like; and rectal suppositories.
The tenus “effective amount or “therapeutically effective amount indudes the amount of the subject compound that will elicit the biological or medical response of a tissue, System, animal or 10 human that is being sought by the researcher, veterinarian, medical doctor or other clinician. As used herein, the term “treatment refers to the treatment of the mentioned conditions, particularly in a patient who demonstrates symptoms of the disease or disorder.
As used herein, the term “treatment or “treating includes any administration of a compound of the présent invention and includes (1) inhibiting the disease in an animal that is experiencing or 15 displaying the pathology or symptomatology of the diseased (i.e., arresting further development of the pathology and/or symptomatology), or (2) ameliorating the disease in an animal that is experiencing or displaying the pathology or symptomatology of the diseased (i.e., reversing the pathology and/or symptomatology). The term “controlling includes preventing treating, eradicating, ameliorating or otherwise reducing the severity of the condition being controlled.
The présent invention described compositions and methods for the treatment of Acquired Immune Deficiency Syndrome (AIDS), using a combination of formulations derived from Aloe vera. The composition of the présent invention includes a stérile injectable polymannan extract, one or more aloe anthraquinones and their dérivatives, and freeze dried aloe powder, aloe juice or an aloe gel. One or more nutritional suppléments are also described that may be given to patients who expérience 25 chronic diarrhea and digestive upsets during the course of the treatment.
The earliest studies evaluating the effect of aloe préparations in AIDS patients were conducted by Terry L. Puise, M.D., who, in the late 1980's conducted a study of 31 HIV-positive patients. Two subjects dropped out of the study, but the extended protocol (six-months) was completed on 29 subjects. The data were published1.
Based on the modified Walter Reed Score, the distribution of the subjects was: Full-blown AIDS: 15 Subjects, AIDS-Related Complex (ARC): 12 Subjects HIV Séropositive: 2 Subjects
The subjects were placed on 1200 mg of total solids in hand-filleted aloe vera juice (6-ounces) daily. In addition, dietary suppléments consisting of essential fatty acids, and a protein-rich, vitaminmineral powder were ingested daily. After six months, 27 of the 29 patients showed improvement on 35 their Walter Reed Scores. Ail had improved Karnofsky Quality of life Scores. T4 cell counts, some originally determined to be less than 200, had climbed to the 400-500 range and a few even as high as 800. HPV P-24 Core antigen dropped with 25% of the réactive patients showing conversion to négative at 90 and 180 days.
Symptomatic Assessment at 6 months: Energy levels improved significantly within 3-5 days of treatment, fevers disappeared, night sweats ceased, coughs decreased significantly or stopped 5 altogether, shortness-of-breath decreased very significantly so some patients were able to résumé their gym workouts, which had been abrogated by their illness, palpable lymph nodes decreased in size, dianhea stopped, strength and stamina improved, and reversai of disease-associated cachexia with a wel corne increase in body weight
A number of patients with chronic dianhea and/or respiratory symptoms, who were no longer 10 employable owing to the severity of the symptoms, were able to résumé their normal employment rôles.
Clinical Assessment: No biochemical abnormalities on the computerized chemistry assessment, AZT-induced anémia was reversed on the aloe/nutritional support regimen, chest radiographs remained normal throughout the study, and showed improvement in a number of patients, and no 15 changes in EKG were noted, significant réduction in reactivity of hypersensitivity skin testing at the end of 90 days.
The current génération of treatment modalities has performed satisfactorily in controlling viremia with significantly increased well-being and increased longevity ofthe patients, however the current treatments are unable to inhibit, in a significant manner, the intracellular réplication cycle of the viral 20 particles. The novel treatment approaches of the présent invention hâve achieved some control improvement in inhibiting the réplication ofthe virus intercellularly.
Polymannan Extract: comprises a very high molecular weight (2 -10 million Daltons) molécules composed predominantly of mannose and glucose with very small amounts of arabinose and galactose. This carbohydrate fraction is produced under U.S. Patent No. 6,083,508 (2000), and 25 further modified by US Provisional Patent No. 61/294,970 which maximizes the capture of a maximum quantity of the very large polysaccharide species. The polysaccharides are partially acetylated, which is a requisite constituent for their potent immunomodulatory activity upon intravenous administration. Upon injection these large molécules bind to mannose receptors on the monocyte/macrophage cells resulting in the élaboration of a suite of cytocommunicators including 30 TNF-α, IL-13, IL-2, IL-6, IFN-γ. These entities restore to normal an impaired/defunct immune surveillance System, stimulate fl lymphocytes (and antibody production), significantly increase the output and availability of naturel killer cells, which, vivo, resuit in very significant anti-tumor and other salubrious activities.1'3
Raidox: comprises a mixture of several small molecular anthraquinone species derived from aloe. 35 These water-soluble molécules are capable of entering the infected T4 cell where it partially disrupts the viral capsule, which abrogates the completion of the réplication cycle. These activities hâve been substantiated in human T4 ccll cultures. The material is administered orally. Limited safety studics ïn some AIDS patients showed no symptoms after oral ingestion of 5 times the rccommcndcd treatment dosage.
Freeze-dried Aloe Powder. comprises an increased quantity of the very large molecular weight carbohydrates, which combine with receptors on the small intestinal mucosal M cells. Once binding has taken place, the M cell uptake of opportunistic ïnfectïous agents is completely blocked. In addition the endocytotic absorption of the large molecular carbohydrates stimulâtes additional release of the cytocommunicators, the process of which is desenbed herein.
Thus the three important advantages of the treatment System of the instant invention include: (i) 10 significant increase in the number ofT4 helper cells, (ii) intraccllular interruption of HIV réplication, and (iiï) prévention of uptake of intestinal opportunistic infectious agents via M cell blockade.
Aloe Polysaccharides added to viral cultures induce viral envelope glycoprotein dysynthesis: Acemannan, an aloe polysaccharide (APS), having a molecular weight range of about 900,000 to 1,500,000 Daltons, was added to HIV-1 infected monocytes cultures and demonstrated that the APS 15 induced the production of multiple molecular wcïghts of HIV-1 envelope glycoprotein, rather than the usual GP-160, GP-120, and GP-41 elcctrophorctic bands. The APS also altcrcd the viral envelope glycoproteins of New Castlc and paramyxoviruses in culture which rendered the virions incapable of înfecting susceptible target cell lines as well as animais.4
Alteration in critical viral envelope structures has therapeutic potential; There are 42 amino acids in 20 the GP-120 segment of the HIV-1 viral envelope. Délétion of 12 amino acids in this région abolishes virion-bindîng capability to the target cell CD-4 receptor site and the substitution of only one amino acid reduces virion binding?
GP-120 in the viral envelope is the critical glycoprotein that détermines the ability of the virion to bind to the CD-4 receptors on susceptible cell membranes. This highly spécifie viral envelope 25 receptor site binding is essentiel for înfecting a host cell.6
The large APS molécules induced endoplasmic réticulum and Golgi dysynthesis of viral envelope glycoprotein and made the viral particle incapable of înfecting susceptible target cells. A further immunomodulatory action of the APS is the increase in the monocytic/macrophagic (M/M) cell counts.7 By contrast with Acemannan (900,000-1,500,000 Daltons), Polymannan Extract (PME) 30 consiste of an array of polysaccharide molecular species (50,000 -10,000,000 Daltons) with the activity of the product largely related to the larger-sized molecular sizes. The dïseoverers of aloeride hâve suggested that the immunomodulatory action of Acemannan is actually due to trace contaminants with aloeride (2,000,000 -10,000,000 Daltons).1
Aloe anthraquinones and AIDS: An Aloe vera leaf consiste of a 15-18 layered outer rind with a 35 protective xylan wax coating. Attached to the undersurface of the thick rind are the vascular bundles surrounded by the thick, gelly-like mucilage layer. The uppermost cells in the vascular bundle are the pcricyclic cells which contain the yellow sap composed of a plethora of potcnt laxative-tnducing anthraquinoncs, which scrved for scveral hundrcd ycars as laxative agents for both man and bcast. These laxative agents bave been largely replaced by gentler laxatives, but some veterinaiy use continues in some countries of the world.
Anthraquinones ïn Aloe barbadensis: Aloe-emodin ( l,8-Dihydroxy-3-(hydraxymethyl-9,10Λ anthracenedione or l,8-Dihydroxy-3-(hydroxymethyl)anthraquinone or 3-Hydroxymethylchrysazin) Aloe-Emodine-Anthranol, Aloinoside-A, Aloinoside-B, Aloin-A (10-Glucopyranosyl-l,S-dihydroxy3-(hydroxymethyl)-9(10)-anthracene or 1,8 -Dihydroxy-3-hydroxymethy 1-10-( 6-hydroxymethyl)-
3,4,5-trihydroxy-2-pyranosyl) anthrone or 10-{l',5'-anhydroglucosyl)-aloe-emodin-9-anthrone or 10 Barbaloin), Aloïn-B - Epimere of Aloïn-A, Isobarbaloin,, Aloinoslde-A, Aloinoside-B, Anthranols,
Anthraquinone-glycocide, Chrysaminic Acid, Chrysophanic Acid, ChrysoDhanol, Chrysophanolglycoside, 1,8-Dihydroxyanthracene, Emodin (l,3,8-Trihydroxy-6-methyl-9,10-anthracene-dione or l,3,8-Trihydroxy-6-methylanthraquinone or 4,5,7-Trihydroxy-2-methylanthraquinone or Frangula emodin), Homonataloin, Hydroxymethylanthraquinone, Rhein (9,10-4,S-Dihydroxy-9,10-dioxo-215 anthracene-caiboxylic acid or l^-Dihydroxyanthraquinone-3-carboxylic acid or 4,5-
Dihydroxyanthraquanone-2-carboxylic acid or Chrysazin-3-carboxylic acid), T rihydroxymethylanthraquinone.
Anthraquinones may be selected from the list, used singly or in various combinations, or from compounds derived from the basic parent compound. In the AIDS therapy program, 50-75 mg of the 20 selected anthraquinone(s) is administered orally to the patient on a daily basis, Le., 25 mg b.i.d or ti.d. These bighly water-soluble moieties are readily absorbed, can enter the HIV-infected CD-4 cell and partially disrupt the viral capsular envelope, which completely prevents completion of the réplication cycle. This modality obviâtes the limitation of various treatment modalitïes whicb are un able or enter to a very limited extent the virion-infccted cell.’ This mechanism and the dysynthesis 25 mechanism, of the large polysaccharides provides a deadly blow to the virions in the infected CD-4 cells.
Aloe vera, Naturel Killer Cells and “M Cell Functions: Aloe vera juice contains about 98% water and 2% total solids, which comprise of over 300 individual constituents, with the single largest component (10-12%) being glucomannan polysaccharides ranging from 50,000 Daltons to 100,00030 Daltons.
When the aloe préparation (liquid or powder) is ïngested, the polysaccharides do not undergo digestive breakdown by amylases, the sugar-digesting enzymes, becausc the glucose and mannose sugars are linked in the beta position. Thus, these large molécules can pass unchanged through the small intestine and the colon.
The small intestinal mucosa consista of approximately 97% fingerlike micro-villi, which significantly increase the surface area for the absorption of digested molécules.. The remaining 3% of the lining cells are M (macromol ecular) cells, which hâve a foldcd, undulating surface, which, through the process of endocytosis (cell-engulfment), permits large molécules and particles to be taken up. When the large polysaccharide molécules exit from the base of the M cell, they immediately corne into contact with mononuclear white blood cells, (macrophages/monocytes) components of the immune 5 system.
The polysaccharides attach to the mannose receptors on the surface of the white cell, which causes the élaboration of a family of immune system factors including TumorNecrosis Factor-alpha (TNFa), Interleukin-lp (IL-β), lnterleukîn-2 (IL-2), Interleukin-6 (IL-6), and gamma interferon (IFN-γ).10
Interleukin-2 (IL-2) stimulâtes the growth and potentiates the cytolytic action of Naturel Killer (NK) 10 cells through the génération of lymphokine-activated killer (LAK) cells, which induce différentiation and prolifération proccsscs. Gamma interferon (INF-γ) is a powerful activator of NK cells.
In AIDS patients the number of M cells may increase significantly (as also occurs with other disease processes involving the gastrointestinal tract) even up to 15-18% compared with the normal 3%. (a) Opportunistic organisms residing in the bowel lumen may gain entrance to the blood stream 15 through the M cell endocytotic uptake. (b) The large molecular polysaccharides in the freeze-dried aloe powder, administered in capsules, passes undigested through the small bowel (owing to the betalinkage of the substituent sugars), and attach to the mannose-binding sites on the M cells. They are taken in to the M cells by endocytosis and exit the M cell base where they encounter monocyte/macrophage (M/M) cells of the immune System where they initïate the sécrétion of the 20 suite of cytocommunicators (TNF-o, IL-Ιβ, IL-2, IL-6, INF-γ) similar to the action of injected PME administered intravenously. (c) Unabsorbed large polysaccharide molécules occupy the endocytic attachment sites, and owing to their large size remain in place for several hours thereby obviating the uptake of opportunistic agents.
Naturel Killer Cells (NK): (i) NK. cells are lymphoid cells of the naturel immune System that express 25 cytotoxicïty against various nucleated cells including tumor cells and virus-infected cells, (ii) NK cells arc believed to represent a significant part of the naturel immune defense against spontancouslydeveloping neoplastic cells and against infection by viruses, (iii) NK. cells do not require programming by prior contact with antigens and are not restricted by the major histocompatability complex (MHC) antigens, (iv) Although NK cells are not phagocytic, they are capable of attacking 30 and destroying malignant tumor cells, (v) Over 150 different types of white cells hâve been identlfied and, of these, NK cells arc one of the most common, representing up to 15% of the total white blood cells. Unlikc other white cells, they arc able to work more or less independently (less programmed), not requiring spécial instructions from the immune system in order to recognize or attack a foreign cell. Thus, they often arc considered to be body's first line of defense against cancer 35 and viral-infected cells, (vi) Circulating through the body by way of the blood and lymph, the majority of NK cells présent in the body arc in a resting but ready state: (a) NK cells are activated by immunoregulatory proteins callcd cytokines. Once activated, the NK cells become quite rapacious in their scarch-and-destroy activities, (b) Upon encountcring a tumor cell, the activated NK cell attaches to the membrane of the cancer or viral cell and injects cytoplasmic granules that quickly dissolve (lyse) the target cell., (e) In less than five minutes the cancer cell is dead and the NK cell moves on to 5 its next victim, (d) Although much smaller in comparison to tumor or viral cells, a single NK cell can ‘ often bind to two or more cancer cells at once, (e) A single NK cell can destroy up to 27 cancer cells before it dies, (vii) The absolutc number of NK cells présent in the blood gives little indication of efïicacy of immune fimetion: (a) Instead, it is NK cell activity - the avidity with which they recognize and bind to tumor or viral cells that is important, (b) Most immunomodulatory substances 10 can empower the NK cells to accentuatc their degree of activity, (c) In healthy immunocompétent individuels, when NK cell activity is examined at an cfiector target ratio of 100:1, NK cell activity ranges from 60-75%, (d) In the cancer patient, NK activity typically ranges from 0 to 30%; the reasons for this sïgnificant décliné are not well understood and remain elusive.
Summary of Therapeutic Mcchanisms in AIDS
I. Polymannan Extract (PME): (a) Inducemcnt of dysynthesis of GP-120 moiety of the virion envelope which abrogates the capacity of the virion to bind to the CD-4 rcceptor, (b) Increase in the number of T4 helper cells, (c) Upon intravenous administration, the large glucomannan polysaccharides attach to mannose receptors on the monocyte/macrophagc cells which induces the élaboration and rclcasc of a suite of cytocommunieators including TNF-a, IL-Ιβ, IL-2, IL-6, and 20 INF-γ. The IL-2 stimulâtes the growth and potentiates the cytolytic action of the Naturel Killer (NK) cells via the génération of lymphokinc-activated killer cells (LAF) which induce différentiation and proliférative processes. INF-γ is a powerful activator of NK cells.
Π. Raidox: (a) The anthraquinone mixture enters the infected T4-helper cells and partially disrupts the viral envelope, which abrogates the réplication cycle. This action is in addition to the dysynthesis 25 of the GP-120 glycoprotcin,
III. Aloe vera freeze dried powder: (a) The large polysaccharides (PS) in aloe liquids, gels, and powders consist of simple hexoses (mannose, glucose, arabinose, and galactose) lihked together in the beta position which proteets these molécules from being amenable to digestion by amylases lcaving these long-chain molécules intact, (b) Oral administration of the powder (contains over 300 30 constituents with the long polysaccharides being the most prominent (10-12% of the total solids)) pennits the PS to bind to the small intestinal M cells and induce the release of the cytoconununicator suite from the M/M located at the base of the M cells, (c) The large PS molécules may remain bound to the M cell mucosal surface for several hours, thereby blocking the uptake by the M cells of opportunistic entities responsable for the untimely deaths of AIDS 35 patients.
Products
I. Polymannan Extract (PME): (a) Availabie as a stérile solution for injection (i.m. and î.v.), (b) Concentration -10 mg/ml, (c) Availabie in 10 ml multidosc vials, and (d) Prescrvativc-0.9% Bcnzyl alcohol, îf desired
Π. Raldox-R (Anthraquinones): (a) Availabie as a selected mixture of anthraquinones, (b) Availabie 5 in vegeaps each containing 25 mg, (c) Availabie in bottles of 60 capsules
III. Freeze-Dried Aloe vera Powden (a) Produced under U.S. Patent No. 6,083,508, (b) Contains no preservatives, (c) Availabie in vegeaps each containing total processed lyophilized aloe vera 400 mg/capsule.
IV. Nutritional Suppléments Many AIDS patients especially those who expérience chronic diarrhea and digestive upsets associated with weight loss, develop malnutrition. Two products are availabie:
(a) GLE/EPA Capsule Ingrédients
Linoleîc Add (LA) 280 mg
Gamma Linolenic Acid (GLA) 80 mg
Eiccsapentaenoic Acid (EPA) 45 mg
Doscosapentaenoic Acid (DPA) 9mg
Docosahcxaenoîc Acid (DHA) 30 mg
(falpba'wcophcrol 15 mg
(b) Powdcr Ingrédients
Instructions for Use of Polymannan Extract
The diagnosis must bc confimied by standard laboratory and other pertinent diagnostic procedures,
e.g. CD4 cell count and circulatîng vira] load in A1DS/HIV, PSA in prostate cancer, pathologica] assay of biopsy specimens, tumor markers, etc. The PME comprises long-chain partially acetylated glucomannan polysaccharides of botanical origin (Aloe barbadensis) having a molecular range of about 100,000 Daltons to 10,000,000 Daltons. This extract possesses very potent immunomodulatory actions. Upon intravenous injection, the PME molécules bind to mannose receptors on the surface membranes of monocytes/macrophages, which results in the secretory élaboration of an array of cytocommunicators, e.g., cytokines, interleukins, interferons, prostaglandins, growth factors, etc., the profile of which varies depending upon the disease entity présent These then, bring about salubriously therapeutic responses in malignant neoplasms, gastrointestina] diseases (e.g., hepatitis C, Chronic ulcerative Colitis, Crohn’s Disease, etc.), vira] diseases (e.g., Epstein-Barr, Lyme's Disease, etc.), as well as increasing beta-lymphocytes and antibodies, and incrcased levels of naturel killer cells.
Additional mannose binding sites are found on the circulatîng protein - Mannose Binding Protein (MBP) which functions as a donor to nascent monocyte/macrophage cellular éléments entering the circulatory system, owing to a greater affinity for PME of the mannose receptors on thèse cells. Studies hâve shown that once PME has been bound to the monocyte/macrophage cellular element, bonding remains in place for about 48 hours, which forms the basis for the thrice weekly intravenous administration treatment schedule.
The PME product is available as a stérile solution for injection in a multi-dose 10 mL via] with a concentration of 10 mg/mL. Owing to the exceptional potency of the product the beginning dosage is 1 mg (0.1 mL). As the product contains no preservatives, exceptionally stringent aseptie conditions must be employed in the administration of PME,
Physiologica] Reaction: Upon intravenous administration, if sufïicient mannose-binding sites are occupied and the resulting cytocommunicator release is adéquate, several proinflammatory moieties,
e.g., Tumor Necrosis Factors-alpha and Interleukin-ΐβ are released which bring ahout an acute phase response (APR) manifested by changes in the hypothalamic temperature-regulating centers, resulting in sensations of chilliness, coldness, shîvering, shakes, and rigors associated with the attempt to satisfy the cytocommunicator- induced resetting of the thermostat This is an expected and désirable physiological reaction, not a side-efTect, as this indicates that the immunomodulatory activités of the monocyte/macrophage cellular éléments hâve been stimulated. The physiological reaction may begin as soon as 30- minutes after injection or take as long as 3-4 hours. Once begun, the entire set of symptoms is usually ahrogated within 1.5 to 2 hours following administration.
In some patients the reaction may produce excessive anxiety. In these situations, the PME may be added to a D-5-W or Normal Saline intravenous infusion, which permits a slower administration with a lessening ofacuity of the physiological response.
If the réactions are still bothersome, the patient may be premedicated an hour before administration using an NSAID, (e.g., 400 - 800 mg Ibuprofen, or similar), which obtunds the symptoms while in no way impairing the resulting immunomodulatory actions induced by the injection.
Factors Influencing the Physiological Response: (i) White blood cell count, (ii) WBC differential 5 respecting the monocyte/macrophage cell count (iii) Number of mannose receptors per monocyte/macrophage, (iv) Proper stcreochcmical configuration of the mannose receptor to enable attachment of the polysaccharide molécules. In some patients who hâve previous received chemotherapy, mannose receptor function may be seriously compromised.
Treatment Schedule: For the initial treatment, 1 mg (0.1 mL) of PME is given one Day 1. On each 10 successive day, the dosage is increased by 0.1 mL (1 milligram), i.e., 0.5 mL (5 milligrams) on Day 5, or until the physiological response is manifest. This procedure is to assure optimal marmose-receptor binding on monocytes/macrophages and the Mannose Binding Protein circulating carrier, and to détermine the dosage necessary to stimulate an adéquate response from the immune System.
Thereafter, treatments are given three times a week increasing the dosage by 1 mg (0.1 mL) of the 15 PME as may be required to maintain a physiological reaction, at least, of some perceptible degree.
Most patients eventually stabilize on a treatment dosage of 10 to 15 mg (1.0 - 1.5 mL) tri weekly. Each patient must be titrated, as each person shows a variability in response to the PME related to variations in WBCs, differential, number of mannose receptors, etc.
Side-effects: Side-effects, including nausea (very occasional vomiting and/or a slight degree of 20 hypotension), occur only with excessive dosages, and with careful management can be entirely avoided. Mild hypotension occurs after the administration of excessively large doses (greater than recommended) which was seen in the Phase I Safety Study. Some patients hâve experienced some joint pain with large doses. Mention has been made previously of administering PME as an infusion of D-5-W or Normal Saline, and/or pre-administration oral ingestion of NSAID médication.
Clinical and Laboratory Evaluations: As each patient îs quite different in the response to PME injections, each patient must be titrated both with respect to the treatment frequency and dosage, and the frequency of clinical and laboratory investigations to assess the progress of the patient and the character of the response to PME administration. Other treatment modalities, e.g., nutritïonal suppléments, low-dose chemotherapeutics, psychological conditioning, etc. may often be employed 3 0 with additional improvement on the part of the patient
It is contemplated that any embodiment discussed in this spécification can be implemented with respect to any method, kit reagent or composition of the invention, and vice versa. Furthermore, compositions ofthe invention can be usedto achieve methods ofthe invention.
It will be understood that particular embodiments described herein are shown by way of illustration 35 and not as limitations of the invention. The principal features of this invention can be employed in various embodiments without departing from the scope ofthe invention. Those skilled in the art will recognize, or be able to asccrtain using no more then routine expérimentation, numerous équivalents to the spécifie procedures described herein. Such équivalents are considered to be within the scope of this invention and are covered by the claims.
Ail publications and patent applications mentioned in the spécification are indicative of the level of skill of those skilled in the art to which this invention pertains. Ail publications and patent applications are herein incorporated by refcrence to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by référencé.
The use of the word “a or “an when used in conjunction with the term “comprising1* in the claims and/or the spécification may mean “one, but it is also consistent with the meaning of “one or more, “at least one,’1 and “one or more than one. The use of the term “or in the claims is used to mean “and/or unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a définition that refers to only alternatives and “and/or. Throughout this application, the term “about is used to indicate that a value includes the inhérent variation of error for the device, the method being employed to détermine the value, or the variation that existe among the study subjects.
As used in this spécification and claim(s), the words “comprising” (and any form of comprising, such as “comprise and “comprises), having (and any form of having, such as hâve and “has), including (and any form of including, such as “includes and “include) or “containing (and any form of containing, such as “contains and “contain”) are inclusive or open-endcd and do not exclude additional, unrecited éléments or method steps.
The term “or combinations thereof’ as used herein refers to ail permutations and combinations of the listed items preceding the term. For example, “A, B, C, or combinations thereof* is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly încluded are combinations that contain repeats of one or more item or term, such as BB, AAA, MB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan will understand that typically there is no lîmit on the number of items or lerms in any combination, unless otherwise apparent from the context. ’
Ail of the compositions and/or methods disclosed and claimed herein can be made and executed without undue expérimentation ïn light of the présent disclosure. While the compositions and methods of this invention hâve been described in lerms of preferred embodiments, il will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. Ail such similar substitutes and modifications apparent to those skilled in the art are decmcd to be within the spirit, scope and concept of the invention as defined by the appended claims.
Référencés
U.S. Patent No. 7,169,414; Antimicrobial Agents Isolated from Aloe Vera.
WIPO Patent No. WO/1993/008810: Uses of Aloe Products, eg. Acemannan, in the 'Treatment of Diseases Requiring Intervention of the Immune System for Cure.
'Puise TL, Uhlig E: A Significant Improvement ta Clinical Pilot Study Utilizing Nutritional Suppléments, Essential Fatty Acids and Stabilized Aloe Vera Juiec in 29 HIVScropositive, ARC and AIDS Patients. Journal of Advanccment in Mcdicine 3(4),1990.
1 Leung MY, Liu C, Zhu LF, Hui VZ, Fung KP: Chemical and biological characterization of a polysaccharide biological response modifier from Aloe vera. Glycobiology 14(6):501-510,2004;
’ Liu C, Leung MY, Koon JC, Zhu LF, Hui VZ, Yu B, Fung KP: MaCTOphage activation by polysaccharide biological response modifiers isolated from Aloe vera 1. var. chtaensis (Haw.) Berg. International Immunopharmacology 6(11):634-641,2006) «Mitchell WM: In vitro évaluation of Acemannan as an anti-HIV-1 agent Carrington Laboratories Research Report 40001-December, 1987.
’Laskey LA, Nakamura G, Smith DH et al: Délinéation of a région of the human immunodeficiency virus Type 1 GP120 glycoprotein critical for interaction with the CD-4 receptor. Cell SO:975-985, 1987.
eChinna AD: Evaluation of the antiviral, adjuvant, and iœmunomodulatory effect of b-(l,4)-ltaeal polymannose (Acemannan). Texas A& M University, College Station, Texas, Diss. Abstr, 1990.
7McDaniel HR et al: An increase ta circulattag monocyte/macrophage (M/M) is induced by Acemannan (ACE-m) ta HTV-1 patients. Amer J Path 94:516-517,1990.
'Pugh N, Ross SA, ElSohly MA, Pasco DS: Characterization of aloeride, a new high25 molecular.weight polysaccharide from Aloe vera with potent immuno-stimulating actîvity. J Agric Food Chem 49(2):1032-1034,2001. .
’Sydiskis RJ, Owen DG, Lohr JL et al: Interaction of enveloped virus by anthraqutaones extracted from plants. Antimierobial Agents and Chemotherapeutics 35:2463-2464, 1991.
IOMY Leung, C Liu, LF Zhu, YZ Hui, KP Fung Chemical and biological characterization of a 30 polysaccharide biological response modifier from Aloe vera L. Glycobiology 14(6):501-510,2004.

Claims (10)

  1. CLATMS
    1. A pharmaceutical composition for use în the treatment, amelioration of symptoms, or both of Acquired Immune Deficiency Syndrome (AIDS) or a HIV infection in a subject, the composition comprising:
    a stérile injectable polymannan extract formulation comprising one or more aloe polysaccharides, wherein the aloe polysaccharides comprise one or more small chain, medium chain, large chain, very-largc chain polysaccharides, or any combinations thereof;
    a formulation comprising one or more aloe anthraquinones, diacetyl anthraquinone dérivatives, and combinations and modifications thereof;
    a formulation comprising a freeze dried aloe powder, an aloe juice, an aloe gel, or a combination wherein the powder is administered as !s or after reconstitution in a suitable liquid; and a formulation comprising one or more optional nutritional suppléments selected from the group consisting of fatty acids, proteins, minerais and métal s, vitamins, salts, amino acids, and other pharmaceutically acceptable excipients.
  2. 2. The composition of claim I, wherein the one or more aloe polysaccharides in the polymannan extract hâve molecular weights ranging from 50,000-10,000,000 Daltons.
  3. 3. The composition of claim 1, wherein the one or more aloe anthraquinones are selected from the group consisting of Aloe-emodin, l,8-Dihydroxy-3-(hydroxymethyl-9,10-anthracenedione, 1,8Dihydroxy-3-(hydroxymethyl)anthraquinone, 3-HydroxymethyIchrysazin, Aloe-Emodine-Anthranol, Aloinoslde-A, Aloinosîde-B, Alotn-A, 10-Glucopyranosyl-I,S-dihydroxy-3-(hydroxymethy 1)-9( 10)anthracene, l,8-Dihydroxy-3-hydroxymethy!-10-(6-hydroxymethyl)-3,4,5-trihydroxy-2-pyranosyl, anthrone, 10-{r,5'-anhydroglucosyl)-aloe-emodin-9-anthronc, Barbaloin, Aloîn-B Epîmere of AloinA, Isobarbaloin,, Aloinoslde-A, Aloinoside-B, Anthranols, Anthraquinone-glycocide, Chrysaminic Acid, Chrysophanic Acid, ChrysoDhanol, Chrysophanol-glycosïde, 1,8-Dihydroxyanthraccnc, Emodîn, 13,8-Trihydroxy-6-methyl-9,10-anthracene-dÎone, l,3,8-Trihydroxy-6methylanthraquînone, 4,5,7-Trihydroxy-2-methylanthraquinone, Frangula emodin, Homonataloin, Hydroxymethylanthraquinone, Rhein, 9,I0-4,5-Dihydroxy-9,10-dioxo-2-anthracene-carboxy!ic acid, I^-Dihydroxyanthraquinone-3-carboxylic acid, 4,5-Dihydroxyanthraquanone-2-carboxylic acid, Chrysazin-3-carboxylic acid, Trihydroxymethylanthraquînone, and modifications and dérivatives thereof.
  4. 4. The composition of claim I, wherein the aloe juice comprises of about 2% total solids.
  5. 5. The composition of claim 1, wherein the one or more fatty acids are selected from the group consisting of Linoleic Acid (LA), Gamma Linolenic Acid (GLA), Eicosapentaneoîc Acid (EPA), Docosapentaneoic Acid (DPA), Docosahexaenoic CAid (DHA), and D-alpha-tocopherol.
  6. 6. The composition of claim 1, wherein the composition further comprises one or more cytocommunicators selected from the group consisting of TNF-a, IL-Ιβ, IL-2, IL-6, and INF-γ, wherein the release stimulâtes the growth and cytoiytic action of one or more Naturel Killer (NK) cells in the subject
  7. 7. Use of a composition as defined in any one of claims 1-6 characterized by being for the manufacture of a médicament for treating, ameliorating symptoms or both of Acquired Immune Deficiency Syndrome (AIDS) or a HIV infection.
  8. 8. A pharmaceutical composition for use în the treatment, amelioration of symptoms or both of Acquired Immune Deficiency Syndrome (AIDS) or a HIV infection in a subject the composition comprising:
    a stérile injectable polymannan extract formulation comprising one or more aloe polysaccharides, wherein the aloe polysaccharides comprise one or more small chain, medium chain, large chain, very-large chain polysaccharides, or any combinations thereof;
    a formulation comprising one or more aloe anthraquinones, diacetyl anthraquinone dérivatives, and combinations and modifications thereof;
    a formulation comprising a freeze dried aloe powder, an aloe juice, an aloe gel or a combination wherein the powder is administered as is or after reconstitution in a suitable liquid; and a formulation of a nutritional supplément comprising 280 mg of Linoleic Acid (LA), 80 mg of Gramma Linoleic Acid (GLA), 45 mg of Eicosapentaenoic Acid (EPA), 9 mg of Doscosapentaenoic Acid (DPA), 30 mg of Docosahexaenoic Acid (DHA) and 15 mg of D-alpha tocopherol.
  9. 9. The composition of claim 8, wherein the one or more aloe anthraquinones are selected from the group consisting of Aloe-cmodin, I,8-Dihydroxy-3-(hydroxymethyl-9,10-anthracenedione, 1,8Dihydroxy-3-(hydroxymethyl)anthraquinone, 3-Hydroxymethylctuysazîn, Aloe-Emodine-Anthranol, A1oinoslde-A, A1oinoside-B, Aloin-A, I0-Glucopyranosyl-I,S-dihydroxy-3-(hydroxymethyl)-9(I0)anthracene, l,8-Dihydroxy-3-hydroxymethyl-I0-(6-hydroxymethyl)-3,4,5-trihydroxy-2-pyranosyl, anthrone, 10-{r,5'-anhydroglucosyl)-aloe-emodin-9-anthrone, Barbaloin, Aloin-B Epimereof AloînA, Isobarbaloin,, Aloinosldc-A, Aloinosidc-B, Anthranols, Anthraquinone-glycocide, Chrysaminic Acid, Chrysophanic Acid, ChrysoDhanol, Chrysophanol-glycoside, 1,8-Dihydroxyanthracene, Emodin, I,3,8-Trihydroxy-6-methyI-9,I0-anthracene-dione, I,3,8-Trihydroxy-6methylanthraquinone, 4,5,7-Trihydroxy-2-methylanthraquinone, Frangula emodin, Homonataloin, Hydroxymethylanthraquinone, Rhein, 9,IO-4,5-Dihydroxy-9,IO-dioxo-2-anthracene-carboxylic acid.
    I, 5-Dihydroxyanthraquinone-3-carboxylîc acid, 4,5-Dihydroxyanthraquanone-2-carboxylic acid, Chrysazin-3-carboxylic acid, Trihydroxymethylanthraquinone, and modifications and dérivatives thereof.
  10. 10. The use of a composition as defined any one of claims 8-9 characterized by being for the manufacture of a médicament for treating, ameliorating symptoms or both of an Acquired Immune Deficiency Syndrome (AIDS) or a HIV infection.
    II. The use of claimlO, wherein the composition releases one or more cytocommunicators selected from the group consisting of TNF-a, IL-Ιβ, IL-2, IL-6, and INF-γ, wherein the release stimulâtes the growth and cytolytic action of one or more Natural Killer (NK) cells in the subject
OA1201300027 2010-07-23 2011-07-20 Anti-viral properties of aloe vera and Aquired Immune Deficiency Syndrome (AIDS) treatment. OA17066A (en)

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