US3729563A - Method of treating movement disorders - Google Patents

Method of treating movement disorders Download PDF

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US3729563A
US3729563A US00096295A US3729563DA US3729563A US 3729563 A US3729563 A US 3729563A US 00096295 A US00096295 A US 00096295A US 3729563D A US3729563D A US 3729563DA US 3729563 A US3729563 A US 3729563A
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dopa
gallate
movement disorders
gallic acid
butyl
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US00096295A
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W Cash
M Weiner
B Petrack
B Manor
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Novartis Corp
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Ciba Geigy Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C65/01—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups
    • C07C65/03—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing hydroxy or O-metal groups monocyclic and having all hydroxy or O-metal groups bound to the ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group

Definitions

  • Gallic acid, its salts and its alkyl esters are utilized S1m1lar responses can be observed in actual clinical in the treatment of involuntary movement disorders.
  • dose of to a 28 Y old compounds can be administered alone or in combination, patlent,suffenng from a Fa Huntlngtons chore? as with LDOPA in the treatment of parkinsonism sulted in a remarkable diminishment of the choreiform movements.
  • tary movement disorders such as parkinsonism, Hunting-
  • the method of treating involuntary movement distons chorea, hyperkinesis, spasmotic torticollis and the orders with gallic acid, its salts and its esters can also like. Treatment of such disorders is elfected through the be practiced in conjunction with other therapy. Most administration of a daily dose of from about 5 mg./kg. importantly, it has been found that gallic acid, its salts to about 25 mg./kg. of a compound of the formula: and its esters potentiate the action of L-DOPA [L-3-(3,4-
  • H0 dihydroxyphenyl)alanine in the treatment of parkin- 30 sonism.
  • L-DOPA is known to be useful in this regard H0 000R but its use is limited by the high doses required and the resultant side effects, particularly choreiform moveo ments, which develop in patients on long term therapy.
  • R is hydrogen or alkyl or from 1 to 9 carbon
  • a pharmaceutically acconjunction with L-DOPA therapy can be observed in ceptable nontoxic alkali metal, alkaline earth metal or l r ry m l as w ll as in r p in a organic amine salt thereof, i.e. a salt of gallic acid.
  • monkey having mesencephalic lesions, doses of L-DOPA Certain of these derivatives are known to have therup to 25 mg./kg. produced no change in the tremor.
  • the present invention is based on the DOPA had no effect, 25 mg./kg. of L-DOPA effected finding that gallic acid, its salts and esters reduce or a cessation of tremor for 30 minutes and a diminished alleviate the physical body movements associated with a tremor for 45 minutes.
  • the butyl gallate when 15 mg./kg. of broad group of conditions generally referred to by the butyl gallate were administered, substantially the same art as involuntary movement disorders.
  • These include the efiiect was obtained with only 15 mg./ kg. of L-DOPA as akinesia, rigidity, tremors associated with parkinsonism, observed for 25 mg./kg. of L-DOPA alone, namely a the dystonic neck movements associated with spasmotic diminished tremor for 40 minutes and a cessation of torticollis, the choreiform movements encountered in tremor for 20 to 30 minutes.
  • Gallic acid, a salt thereof or an ester thereof 'prferably administered orally as a treatment for involuntary movement disorders This can be accomplished through the use of any of the usual pharmaceutical forms, in-' cluding solid and liquid unit oral dosage forms such as tablets, capsules, powders, suspensions, solutions, syrups and the like, including sustained release preparations.
  • unit dosage form as used in this specification and the claims refer to physically discrete units to be administered in single or multiple dosage to humans, each unit containing a predetermined quantity of active materials in association with the required diluent, carrier or vehicle. The quantity of active material is that calcu lated to produce the desired therapeutic elfect upon administration of one or more of such units in a single or multiple dose regimen.
  • Powders are prepared by comminuting gallic acid, a salt thereof or an ester thereof to a suitably fine size and mixing with a similarly comminuted diluent pharmaceutical carrier' such as an edible carbohydrate material as for example, starch. sweetening, flavoring, preservative, dispersing and coloring agents can also be present.
  • a similarly comminuted diluent pharmaceutical carrier' such as an edible carbohydrate material as for example, starch. sweetening, flavoring, preservative, dispersing and coloring agents can also be present.
  • Capsules are made by preparing a powder mixture as described above and filling formed gelatin sheaths.
  • a lubricant such as talc, magnesium stearate and calcium stearate can be added to the powder mixture as an ad juvant before the filling operation;
  • a glidant such as colloidal silica may be added to improve flow properties;
  • a disintegrating or solubilizing agent may be added to improve the availability of the medicament when the capsule is ingested.
  • Tablets are made by preparing a powder mixture, granulating or slugging, adding a lubricant and disintegrant and pressing into tablets.
  • a powder mixture is prepared by mixing the compound, suitably comminuted, with a diluent or base such as starch, sucrose, kaolin, dicalcium phosphate and the like.
  • the powder mixture can be granulated by wetting with a binder such as syrup, starch paste, acacia mucilage or solutions of cellulosic or polymeric materials and forcing through a screen.
  • a binder such as syrup, starch paste, acacia mucilage or solutions of cellulosic or polymeric materials and forcing through a screen.
  • the powder mixture can be run through the tablet machine and the resulting imperfectly formed slugs broken into granules.
  • the granules can be lubricated to prevent sticking to the tablet forming dies by means of the addition of stearic acid, a stearate salt, talc or mineral oil.
  • the lubricated mixture is then compressed into tablets, the medicaments canialso be combined with free flowing inert carriers and compressed into tablets directly without going through the granulating or slugging steps.
  • a protective coating consisting of a sealing coat of shellac,'a coating of sugar or polymericmaterial and a polish coating of wax can be provided. Dyestufl's can be added to these coatings to distinguish ditferent unit dosages.
  • Oral fluids such as syrups and elixirs can be prepared in unit dosage form so that a given quantity, e.g., a teaspoonful, contains a predetermined amount of the compound.
  • Syrups can be prepared by dissolving the compound vin a suitably flavored aqueous sucrose solution while elixirs are prepared through the use of a non-toxic alcoholic vehicle.
  • Suspensions can be formulated by dispersing the medicament in a non-toxic vehicle in which it is insoluble.
  • gallic acid, a salt thereof or an ester thereof When utilized-alone, gallic acid, a salt thereof or an ester thereof is generally administered in a single or multiple dose regimen so that the patient receives a daily dose of from about mg./kg. to about 25 mgJkg.
  • This range is however merely a guideline for in all cases the actual dose must be adjusted to the age, weight and condition of the patient and most importantly, titrated to the response observed.
  • a human Ingredient for example, for a human Ingredient:
  • gallic acid a salt thereof or an alkyl ester thereof.
  • the salts are those derived from alkali metals, alkaline earth metals or organic amines, such as the sodium, potassium, calcium and those of ammonia, ethylamine, triethylamine, ethanolamine, diethylarninoethanol, ethylenediamine, piperidine, morpholine, 2-(piperidino )-ethanol, benzylamine, procaine and the like.
  • Esters are those derived from gallic acid and straight or branched chain alcohols having from 1 to 9 carbon atoms,-such as methyl gallate, ethyl gallate, n-propyl gallate, isopropyl gallate, n-butyl gallate, pentyl gallate, hexyl gallate, octyl gallate, nonyl gallate and the like.
  • the preferred form of gallic acid for the practice of the present invention is the npropyl and n-butylesters.
  • lactose, corn starch and Cab-O-Sil are blended and granulated with an alcoholic solution of the stearic acid. This granulate is blended with the butyl gallate and the resulting blend is encapsulated in #0 capsules.
  • the foregoing ingredients are combined in accordance with the procedure described in Example 4 and pressed into tablets suitable for oral administration of 50 mg. of L-DOPA and 300 mg. of propyl gallate.
  • the first four ingredients are thoroughly mixed and granulated with a aqueous solution of soluble starch. This granulate is dried, mixed with magnesium stearate and pressed into tablet cores which are coated with sugar.
  • R is hydrogen or alkyl of from 1 to 9 carbon atoms, or 'when R is hydrogen, a pharmaceutically acceptable non-toxic alkali metal, alkaline earth metal or organic amine salt thereof.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

GALLIC ACID, ITS SALTS AND ITS ALKYL ESTERS ARE UTILIZED IN THE TREATMENT OF INVOLUNTARY MOVEMENT DISORDERS. THE COMPOUNDS CAN BE ADMINISTERED ALONE OR IN COMBINATION, AS WITH L-DOPA IN THE TREATMET OF PARKINSONISM.

Description

United States Patent 3,729,563 Patented Apr. 24, 1973 ment disorders can be conveniently observed in laboratory models utilizing, for example, monkeys with mesencephalic lesions. In this method, described by Goldstein et al., Proc. Nat. Acad. Science, 63, No. 4, 1113 (1969) unilateral radio frequency lesions are induced in No Drawing. Continuation-impart of application Ser. No. 5 the Flmmal which then develops hypokinesia almost s,940, Jan. 26, 1970. This application Dec. 8, 1970, modlately and a resting tremor Within a week, a y a Ser.No. 96,295 drome comparable to the neuropathological profile en- Int. Cl. A61k 27/00 countered in human parkinsonism. After administration 424-243 3 Clalms of a dose of 50 mg./kg. of butyl gallate, the tremor diminishes or completely disappears for a period of one ABSTRACT OF THE DISCLOSURE to two hours.
Gallic acid, its salts and its alkyl esters are utilized S1m1lar responses can be observed in actual clinical in the treatment of involuntary movement disorders. The i Thus dose of to a 28 Y old compounds can be administered alone or in combination, patlent,suffenng from a Fa Huntlngtons chore? as with LDOPA in the treatment of parkinsonism sulted in a remarkable diminishment of the choreiform movements. In a second patient, a 43 year old female CROSS REFERENCE with a six year progressive history of chorea and a family background of Huntingtons chorea, choreiform Thls 1S a commuatlon'm'part of 5940 filed movements ceased and remained absent upon treatment 1970' with butyl gallate. A third patient with spasmodic torti- DETAILED DESCRIPTION collis, when placed on 250 mg. t.i.d. had almost complete This invention pertains to the treatment of involuncessation of dystonic neck movements. tary movement disorders such as parkinsonism, Hunting- The method of treating involuntary movement distons chorea, hyperkinesis, spasmotic torticollis and the orders with gallic acid, its salts and its esters can also like. Treatment of such disorders is elfected through the be practiced in conjunction with other therapy. Most administration of a daily dose of from about 5 mg./kg. importantly, it has been found that gallic acid, its salts to about 25 mg./kg. of a compound of the formula: and its esters potentiate the action of L-DOPA [L-3-(3,4-
H0 dihydroxyphenyl)alanine] in the treatment of parkin- 30 sonism. L-DOPA is known to be useful in this regard H0 000R but its use is limited by the high doses required and the resultant side effects, particularly choreiform moveo ments, which develop in patients on long term therapy.
wherein R is hydrogen or alkyl or from 1 to 9 carbon The value of the utilization of these compounds in atoms, or, when R is hydrogen, a pharmaceutically acconjunction with L-DOPA therapy can be observed in ceptable nontoxic alkali metal, alkaline earth metal or l r ry m l as w ll as in r p in a organic amine salt thereof, i.e. a salt of gallic acid. monkey having mesencephalic lesions, doses of L-DOPA Certain of these derivatives are known to have therup to 25 mg./kg. produced no change in the tremor. At apeutic activity. For example, Sakurai et al., J. Pharm. half this dose of L-DOPA however, 12.5 mg./kg., when Soc. Japan, 69, 434 (1949) describe some anthelmintic administered with either 10 or 15 mg./kg. of butyl galactivity for several alkyl gallates. US. Pat. No. 3,462,534 late, the tremor diminished for 40 minutes. When 12.5 describes psychotherapeutic activity, specifically antimg./kg. of L-DOPA was administered with 20 mg./kg. depressant properties, for alkyl gallates and gallacetol. of butyl gallate, the tremor ceased for from 40 to 60 -In contrast to the latter use which involves exclusively minutes. In a second monkey, while 15 mg./kg. of L- mental disorders, the present invention is based on the DOPA had no effect, 25 mg./kg. of L-DOPA effected finding that gallic acid, its salts and esters reduce or a cessation of tremor for 30 minutes and a diminished alleviate the physical body movements associated with a tremor for 45 minutes. However when 15 mg./kg. of broad group of conditions generally referred to by the butyl gallate were administered, substantially the same art as involuntary movement disorders. These include the efiiect was obtained with only 15 mg./ kg. of L-DOPA as akinesia, rigidity, tremors associated with parkinsonism, observed for 25 mg./kg. of L-DOPA alone, namely a the dystonic neck movements associated with spasmotic diminished tremor for 40 minutes and a cessation of torticollis, the choreiform movements encountered in tremor for 20 to 30 minutes.
Huntingtons chorea and a variety of movement disor- In actual clinical tests, these compounds have been ders resulting from extrapyramidal dysfunction. shown to be effective in combatting the dose-related toxic Moreover, in contrast to the use of certain alkyl galeffects of L-DOPA therapy. In nine patients, for example, lates as anthelmintics, these compounds to date have extreated with a daily dose of 750 mg. of butyl gallate, not hibited no side effects when administered according to only was there a significant reduction in the dose of L- the described method of utilizing the present invention. DOPA required, but also a remarkable decrease in un- The activity of these compounds on involuntary movewanted side-effects, as shown in Table I.
TABLE I -LDOPA L-DOPA and butyl gallate Patient ABODEFGHIJ'ABCDEFGHIJ DoseL-DOPA(gra.ms) 1.5 2.5 5 5 6 7 5 6 4 6 1.0 2.0 2.0 2.0 5 3 4 4 5 Al'mnrmnl 10131032210000001000 14110121010000000000 13133233230001011111 03023122210001101010 13012213221101110111 20030010110001001011 10000000200000000000 12021212210101011110 NOTE.-0=n0 observable abnormality; 1=minimal abnormality; 2=minimal to moderate abnormality; 3=moderate to severe abnormality; 4= maximal abnormality.
Gallic acid, a salt thereof or an ester thereof 'prferably administered orally as a treatment for involuntary movement disorders. This can be accomplished through the use of any of the usual pharmaceutical forms, in-' cluding solid and liquid unit oral dosage forms such as tablets, capsules, powders, suspensions, solutions, syrups and the like, including sustained release preparations. The term unit dosage form as used in this specification and the claims refer to physically discrete units to be administered in single or multiple dosage to humans, each unit containing a predetermined quantity of active materials in association with the required diluent, carrier or vehicle. The quantity of active material is that calcu lated to produce the desired therapeutic elfect upon administration of one or more of such units in a single or multiple dose regimen.
Powders are prepared by comminuting gallic acid, a salt thereof or an ester thereof to a suitably fine size and mixing with a similarly comminuted diluent pharmaceutical carrier' such as an edible carbohydrate material as for example, starch. sweetening, flavoring, preservative, dispersing and coloring agents can also be present.
Capsules are made by preparing a powder mixture as described above and filling formed gelatin sheaths. A lubricant such as talc, magnesium stearate and calcium stearate can be added to the powder mixture as an ad juvant before the filling operation; a glidant such as colloidal silica may be added to improve flow properties; a disintegrating or solubilizing agent may be added to improve the availability of the medicament when the capsule is ingested.
Tablets are made by preparing a powder mixture, granulating or slugging, adding a lubricant and disintegrant and pressing into tablets. A powder mixture is prepared by mixing the compound, suitably comminuted, with a diluent or base such as starch, sucrose, kaolin, dicalcium phosphate and the like. The powder mixture can be granulated by wetting with a binder such as syrup, starch paste, acacia mucilage or solutions of cellulosic or polymeric materials and forcing through a screen. As an alternative to granulating, the powder mixture can be run through the tablet machine and the resulting imperfectly formed slugs broken into granules. The granules can be lubricated to prevent sticking to the tablet forming dies by means of the addition of stearic acid, a stearate salt, talc or mineral oil. The lubricated mixture is then compressed into tablets, the medicaments canialso be combined with free flowing inert carriers and compressed into tablets directly without going through the granulating or slugging steps. A protective coating consisting of a sealing coat of shellac,'a coating of sugar or polymericmaterial and a polish coating of wax can be provided. Dyestufl's can be added to these coatings to distinguish ditferent unit dosages.
Oral fluids such as syrups and elixirs can be prepared in unit dosage form so that a given quantity, e.g., a teaspoonful, contains a predetermined amount of the compound. Syrups can be prepared by dissolving the compound vin a suitably flavored aqueous sucrose solution while elixirs are prepared through the use of a non-toxic alcoholic vehicle. Suspensions can be formulated by dispersing the medicament in a non-toxic vehicle in which it is insoluble.
When utilized-alone, gallic acid, a salt thereof or an ester thereof is generally administered in a single or multiple dose regimen so that the patient receives a daily dose of from about mg./kg. to about 25 mgJkg. This range is however merely a guideline for in all cases the actual dose must be adjusted to the age, weight and condition of the patient and most importantly, titrated to the response observed. Thus, for example, for a human Ingredient:
' 'Whefi utiliied in conjunction with IrDOPA'therapy;
and then begin the administration of the gallic acid, salt,
or ester. In: this fashion, the required close of L-DOPA, which will vary from patient to patient, can be significantly reduced with, as described above, a significant reduction of elimination of side effects.
In the Practice of this method, one can employ gallic acid, a salt thereof or an alkyl ester thereof. The salts are those derived from alkali metals, alkaline earth metals or organic amines, such as the sodium, potassium, calcium and those of ammonia, ethylamine, triethylamine, ethanolamine, diethylarninoethanol, ethylenediamine, piperidine, morpholine, 2-(piperidino )-ethanol, benzylamine, procaine and the like. Esters are those derived from gallic acid and straight or branched chain alcohols having from 1 to 9 carbon atoms,-such as methyl gallate, ethyl gallate, n-propyl gallate, isopropyl gallate, n-butyl gallate, pentyl gallate, hexyl gallate, octyl gallate, nonyl gallate and the like. The preferred form of gallic acid for the practice of the present invention is the npropyl and n-butylesters.
The following examples will serve to further typify the nature ofthe present invention but should not be construed as a limitation thereof.
The lactose, corn starch and Cab-O-Sil are blended and granulated with an alcoholic solution of the stearic acid. This granulate is blended with the butyl gallate and the resulting blend is encapsulated in #0 capsules.
EXAMPLE 2 Quantity/capsule, mg. Butyl gallate 8O Corn starch 80 The two ingredients are thoroughly blended and encapsulated in #4 capsules.
of average weight of 70 kg, if an .initial daily dose of about 500- mg. does not produce a satisfactory response,
w g ss s qbss vsdt EXAMPLE 3 Ingredient: Quantity/capsule, mg. L-DOPA Butyl gallate 200 Corn starch 500 The foregoing ingredients are mixed and introduced into a two-piece #1 hard gelatin capsule.
The.L-DOPA,butyl gallate, corn starch and lactose .are thoroughly blended and granulated with a 10% aqueaus solution of gel'atinQThe Wet granulate is dried, screened and combined with the Cab-O-Sil and magnesiurn stearate. This mixture is pressed into tablets suitable for oral administration of 100 mg. of L-DOPA and 300 mg. of butyl gallate. The tablets may be scored to permit he admi is rat on of fractional doses EXAMPLE 5 Ingredient: Quantity/capsule, mg. L-DOPA 500 Propyl gallate 300 Corn starch 200 Lactose 200 Cab-O-Sil M5 400 Gelatin 5 Magnesium stearate 1 The foregoing ingredients are combined in accordance with the procedure described in Example 4 and pressed into tablets suitable for oral administration of 50 mg. of L-DOPA and 300 mg. of propyl gallate.
The first four ingredients are thoroughly mixed and granulated with a aqueous solution of soluble starch. This granulate is dried, mixed with magnesium stearate and pressed into tablet cores which are coated with sugar.
What is claimed is:
1. The method of treating involuntary movement disorders which comprises orally administering to a human suffering from such disorder in a single or multiple dosage regimen, a daily dose of from about 5 mg./kg. to about 25 mg./kg. of a compound of the formula:
HO 000R wherein R is hydrogen or alkyl of from 1 to 9 carbon atoms, or 'when R is hydrogen, a pharmaceutically acceptable non-toxic alkali metal, alkaline earth metal or organic amine salt thereof.
2. The method of claim 1 wherein R is propyl.
3. The method of claim 1 wherein R is butyl.
References Cited UNITED STATES PATENTS 3,462,534 8/1969 Greengard et a1 424308 STANLEY I. FRIEDMAN, Primary Examiner US. Cl. X.R.
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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3911137A (en) * 1972-12-11 1975-10-07 Sankyo Co Process for preparing highly concentrated aqueous solution of a dopa compound
US3928589A (en) * 1973-08-08 1975-12-23 Upjohn Co Novel method and compositions
US3984535A (en) * 1970-07-24 1976-10-05 L'oreal Scalp deodorant composition
US20010047032A1 (en) * 1999-12-30 2001-11-29 Castillo Gerardo M. Polyhydroxylated aromatic compounds for the treatment of amyloidosis and alpha-synuclein fibril diseases
EP1808169A2 (en) 1999-12-30 2007-07-18 Proteotech Inc. Polyhydroxylated aromatic compounds for the treatment of amyloidosis and alpha-synuclein fibril diseases
WO2011091692A1 (en) * 2010-01-29 2011-08-04 浙江大学 Uses of benzoate and its derivatives

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3984535A (en) * 1970-07-24 1976-10-05 L'oreal Scalp deodorant composition
US3911137A (en) * 1972-12-11 1975-10-07 Sankyo Co Process for preparing highly concentrated aqueous solution of a dopa compound
US3928589A (en) * 1973-08-08 1975-12-23 Upjohn Co Novel method and compositions
US20010047032A1 (en) * 1999-12-30 2001-11-29 Castillo Gerardo M. Polyhydroxylated aromatic compounds for the treatment of amyloidosis and alpha-synuclein fibril diseases
EP1808169A2 (en) 1999-12-30 2007-07-18 Proteotech Inc. Polyhydroxylated aromatic compounds for the treatment of amyloidosis and alpha-synuclein fibril diseases
EP1808169A3 (en) * 1999-12-30 2008-03-19 Proteotech Inc. Polyhydroxylated aromatic compounds for the treatment of amyloidosis and alpha-synuclein fibril diseases
WO2011091692A1 (en) * 2010-01-29 2011-08-04 浙江大学 Uses of benzoate and its derivatives
CN103118677A (en) * 2010-01-29 2013-05-22 浙江大学 Application of benzoate and its derivatives

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