WO2009047826A2 - Pharmaceutical composition comprising sucralphate and mesalazine - Google Patents

Pharmaceutical composition comprising sucralphate and mesalazine Download PDF

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Publication number
WO2009047826A2
WO2009047826A2 PCT/IT2008/000639 IT2008000639W WO2009047826A2 WO 2009047826 A2 WO2009047826 A2 WO 2009047826A2 IT 2008000639 W IT2008000639 W IT 2008000639W WO 2009047826 A2 WO2009047826 A2 WO 2009047826A2
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Prior art keywords
weight
composition according
lesions
sucralphate
mesalazine
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PCT/IT2008/000639
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French (fr)
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WO2009047826A8 (en
WO2009047826A3 (en
Inventor
Domenico Russo
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Tuttofarmaco S.R.L.
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Publication of WO2009047826A3 publication Critical patent/WO2009047826A3/en
Publication of WO2009047826A8 publication Critical patent/WO2009047826A8/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • 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
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/606—Salicylic acid; Derivatives thereof having amino groups
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7024—Esters of saccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0031—Rectum, anus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Definitions

  • composition comprising sucralphate and mesalazine
  • the present invention relates to pharmaceutical formulations comprising sucralphate and mesalazine (5-ASA) .
  • Sucralphate is an amorphous complex of aluminium hydroxide and sucrose sulphate, identified by the name: ⁇ -D-fructofuranosyl- ⁇ -D-glucopyranoside ottakis (hydrogen sulphate) aluminium complex.
  • sucralphate as an active ingredient are currently employed as medicaments for the cure of gastric and gastroduodenal ulcers.
  • sucralphate has the ability to inhibit pepsin activity, to create a protective layer preventing the hydrochloric acid action on the gastric mucosal membrane, and to bind to the bile salts, thus neutralizing the aggression thereof against the same mucosal membrane.
  • mesalazine, or 5-amino salicylic acid (5-ASA) is currently employed in the therapy of intestinal inflammatory' diseases, such as ulcerative colitis and Crohn's disease.
  • intestinal inflammatory' diseases such as ulcerative colitis and Crohn's disease.
  • mesalazine is employed to "turn off" inflammation, both during the steps of recurrence of the desease, and during the remission steps, in order to reduce the risk of new reappearances.
  • 5-ASA in a tablet form always at high dosages, can be useful in those forms of Crohn's disease in the reappearance step.
  • these therapies it is possible to induce the complete disappearance of symptoms only in a reduced pergentage of patients, to the extent that many specialists prefer to begin the cure directly with cortisone drugs.
  • mesalazine results to be efficient in the treatment of intestinal diseases only under those particular cases set forth above.
  • the problem underlying the present invention is to provide pharmaceutical compositions which have a superior activity compared to that of the known actives in the prevention and treatment of intestinal diseases.
  • the above-mentioned problem is solved by a composition comprising the mesalazine and sucralphate associaction as outlined in the annexed claims .
  • the Applicant of the present application has surprisingly found that the sucralphate and mesalazine associaction has a synergical effect in the treatment of particular diseases of the rectum.
  • diseases are selected from the group consisting of: actinic proctitis, diversion proctitis, aphthoid lesions of the rectum caused by avitaminosis or viruses, rhagades, fistulizing lesions, solitary ulcer of the rectum, hemorrhoids, anal itching.
  • Other diseases against which the composition resulted to be active are: rectal lesions caused by endoscopic dilatation, lesions of the rectum caused by radiotherapy or chemotherapy.
  • the present invention relates to a composition
  • a composition comprising s ⁇ cralphate in an amount ranging from 0.1 to 99% by weight, and mesalazine in an amount ranging from 99% to 0.1% formulated, together with pharmacologically acceptable excipients, as a gel, cream, enema, or rectal suppository for an internal or perianal application.
  • composition of the invention comprises sucralphate preferably in an amount from 0.5 to 50% by weight, more preferably from 1 to 10% by weight, still more preferably from 1 to 8% by weight.
  • Mesalazine is preferably included in an amount from 0.01 to 20% by weight, more preferably from 0.05% to 10% by weight, still more preferably from 0.5% to 5% by weight.
  • composition of the invention may comprise further actives selected from the group consisting of: grapefruit seed extract, methyl sulfonyl methane (MSM) , lactic acid, glycine, vitamins, and mixtures of two or more thereof.
  • MSM methyl sulfonyl methane
  • Each of the above-mentioned actives when included in the composition of the invention, is present in an amount from 0.01 to 10% by weight, preferably from 0.5 to 8% by weight, more preferably from 1 to 5% by weight.
  • the pharmacologically acceptable excipients usable in the formulation as a gel, cream, enema, or rectal suppository are selected from the group consisting of glycerine, Vaseline, anhydrous lanolin, shark liver oil, sodium saccharinate, menthol, sweet almond oil, sorbitol, sodium benzoate, anoxid SBN, vanilla essential oil, aerosol, parabens in phenoxyethanol, sodium methyl p-oxybenzoate, sodium propyl p-oxybenzoate, diethylamine, carbomers, macrogol cetostearyl ether, cocoyl caprylocaprate, isopropyl alcohol, propylene glycol, liquid paraffin, xanthan gum, carboxy-metabisulfite, sodium edetate, sodium benzoate, potassium metabisulfite, potassium acetate, and mixtures of two or more components thereof.
  • the pharmaceutically acceptable excipients are employed in the formulations of the invention in the amounts typically used in the field, and which are known to those skilled in the art.
  • composition of the invention formulated as a gel, cream, enema, or rectal suppository according to the needs, proved to be active in the prevention and cure of the following diseases: actinic proctitis, diversion proctitis, aphthoid lesions of the rectum caused by avitaminosis or viruses, rhagades, fistulizing lesions, solitary ulcer of the rectum, haemorrhoids, anal itching.
  • Other diseases against which the composition resulted to be active are: rectal lesions caused by endoscopic dilatation, lesions of the rectum caused by radiotherapy or chemotherapy.
  • sucralphate is formulated with one or more actives selected from: grapefruit seed extract, methyl sulfonyl methane (MSM) , lactic acid, glycine, vitamins, in particular vitamin A and E, but moreover when it is associated to mesalazine.
  • MSM methyl sulfonyl methane
  • the grapefruit seed extract has an antibacterial and antiviral action, in particular against Escherichia coli. In fact, it protects the inflamed and infected sites. Methyl sulfonyl methane has an intense pain- killing action, associated to an antioxidant and anti-inflammatory action.
  • Lactic acid restores the acidic pH altered by the inflammatory processes and the bacterial flora unbalance .
  • Glycine the simplest amino acid, aids to restore the tissue proteins.
  • Vitamins C and E have an antioxidant and antiinflammatory activity.
  • composition of the invention contains one or more of the actives listed above, it also has an antioxidant and anti-inflammatory effect, beside the cure and prevention activity for the intestinal diseases described above.
  • composition formulated as a gel, cream, or rectal suppository will have to be externally applied, at the perianal region, twice daily or more often, until complete recovery; or, by means of a special applicator, into the internal rectal area twice daily or more often, until complete recovery.
  • compositions and formulation of the invention are set forth below.
  • Excipients diethylamine, carbomers, macrogol cetostearyl ether, cocoyl caprylocaprate, isopropyl alcohol, liquid paraffin, propylen glycol, filtered water .

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Engineering & Computer Science (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Cardiology (AREA)
  • Alternative & Traditional Medicine (AREA)
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  • Botany (AREA)
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Abstract

The invention relates to a pharmaceutical composition comprising sucralphate and mesalazine, and formulated as a gel, cream, enema, or rectal suppository. The use of this formulation is for the treatment of diseases such as actinic proctitis, diversion proctitis, aphthoid lesions of the rectum caused by avitaminosis or viruses, rhagades, fistulizing lesions, solitary ulcer of the rectum, haemorrhoids, anal itching. Other possible applications relate to the use in the treatment of rectal lesions caused by endoscopic dilatation, lesions of the rectum caused by radiotherapy or chemotherapy.

Description

DESCRIPTION
Pharmaceutical composition comprising sucralphate and mesalazine
*** * * * * *
The present invention relates to pharmaceutical formulations comprising sucralphate and mesalazine (5-ASA) .
Sucralphate is an amorphous complex of aluminium hydroxide and sucrose sulphate, identified by the name: β-D-fructofuranosyl-α-D-glucopyranoside ottakis (hydrogen sulphate) aluminium complex.
Pharmaceutical compositions containing sucralphate as an active ingredient are currently employed as medicaments for the cure of gastric and gastroduodenal ulcers. In fact, sucralphate has the ability to inhibit pepsin activity, to create a protective layer preventing the hydrochloric acid action on the gastric mucosal membrane, and to bind to the bile salts, thus neutralizing the aggression thereof against the same mucosal membrane.
Mesalazine, or 5-amino salicylic acid (5-ASA) is currently employed in the therapy of intestinal inflammatory' diseases, such as ulcerative colitis and Crohn's disease. In both diseases, mesalazine is employed to "turn off" inflammation, both during the steps of recurrence of the desease, and during the remission steps, in order to reduce the risk of new reappearances. However, there are some important differences, as regards the indications of use for this drug, between the two diseases.
The therapy with this drug is indicated, during the recurrence steps, only in those forms of ulcerative colitis which are not considered "serious": for the serious forms, it is in fact necessary to use more powerful drugs.
5-ASA in a tablet form, always at high dosages, can be useful in those forms of Crohn's disease in the reappearance step. However, with these therapies it is possible to induce the complete disappearance of symptoms only in a reduced pergentage of patients, to the extent that many specialists prefer to begin the cure directly with cortisone drugs.
Therefore, mesalazine results to be efficient in the treatment of intestinal diseases only under those particular cases set forth above.
Therefore, there is the need to find new pharmaceutical compositions which prove to be particularly active in the cure of rectum diseases. Therefore, the problem underlying the present invention is to provide pharmaceutical compositions which have a superior activity compared to that of the known actives in the prevention and treatment of intestinal diseases. The above-mentioned problem is solved by a composition comprising the mesalazine and sucralphate associaction as outlined in the annexed claims .
The Applicant of the present application has surprisingly found that the sucralphate and mesalazine associaction has a synergical effect in the treatment of particular diseases of the rectum. Such diseases are selected from the group consisting of: actinic proctitis, diversion proctitis, aphthoid lesions of the rectum caused by avitaminosis or viruses, rhagades, fistulizing lesions, solitary ulcer of the rectum, hemorrhoids, anal itching. Other diseases against which the composition resulted to be active are: rectal lesions caused by endoscopic dilatation, lesions of the rectum caused by radiotherapy or chemotherapy.
Sucralphate, which has already been found to be efficient against the above-mentioned diseases, has a synergically increased activity when empolyed in combination with mesalazine. In a first aspect thereof, the present invention relates to a composition comprising sυcralphate in an amount ranging from 0.1 to 99% by weight, and mesalazine in an amount ranging from 99% to 0.1% formulated, together with pharmacologically acceptable excipients, as a gel, cream, enema, or rectal suppository for an internal or perianal application.
The composition of the invention comprises sucralphate preferably in an amount from 0.5 to 50% by weight, more preferably from 1 to 10% by weight, still more preferably from 1 to 8% by weight. Mesalazine is preferably included in an amount from 0.01 to 20% by weight, more preferably from 0.05% to 10% by weight, still more preferably from 0.5% to 5% by weight.
In a preferred aspect, the composition of the invention may comprise further actives selected from the group consisting of: grapefruit seed extract, methyl sulfonyl methane (MSM) , lactic acid, glycine, vitamins, and mixtures of two or more thereof.
Each of the above-mentioned actives, when included in the composition of the invention, is present in an amount from 0.01 to 10% by weight, preferably from 0.5 to 8% by weight, more preferably from 1 to 5% by weight.
The pharmacologically acceptable excipients usable in the formulation as a gel, cream, enema, or rectal suppository, are selected from the group consisting of glycerine, Vaseline, anhydrous lanolin, shark liver oil, sodium saccharinate, menthol, sweet almond oil, sorbitol, sodium benzoate, anoxid SBN, vanilla essential oil, aerosol, parabens in phenoxyethanol, sodium methyl p-oxybenzoate, sodium propyl p-oxybenzoate, diethylamine, carbomers, macrogol cetostearyl ether, cocoyl caprylocaprate, isopropyl alcohol, propylene glycol, liquid paraffin, xanthan gum, carboxy-metabisulfite, sodium edetate, sodium benzoate, potassium metabisulfite, potassium acetate, and mixtures of two or more components thereof. Other pharmaceutically acceptable excipients typically employed in the preparation of a gel, cream, or rectal suppository or solutions can be used in the present invention.
The pharmaceutically acceptable excipients are employed in the formulations of the invention in the amounts typically used in the field, and which are known to those skilled in the art.
The composition of the invention, formulated as a gel, cream, enema, or rectal suppository according to the needs, proved to be active in the prevention and cure of the following diseases: actinic proctitis, diversion proctitis, aphthoid lesions of the rectum caused by avitaminosis or viruses, rhagades, fistulizing lesions, solitary ulcer of the rectum, haemorrhoids, anal itching. Other diseases against which the composition resulted to be active are: rectal lesions caused by endoscopic dilatation, lesions of the rectum caused by radiotherapy or chemotherapy.
It has been observed that the activity of prevention and cure of the above-mentioned diseases results to be synergically increased not only when sucralphate is formulated with one or more actives selected from: grapefruit seed extract, methyl sulfonyl methane (MSM) , lactic acid, glycine, vitamins, in particular vitamin A and E, but moreover when it is associated to mesalazine.
These actives proved to have further pharmacological actions, besides enhancing the efficiency of sucralphate.
The grapefruit seed extract has an antibacterial and antiviral action, in particular against Escherichia coli. In fact, it protects the inflamed and infected sites. Methyl sulfonyl methane has an intense pain- killing action, associated to an antioxidant and anti-inflammatory action.
Lactic acid restores the acidic pH altered by the inflammatory processes and the bacterial flora unbalance .
Glycine, the simplest amino acid, aids to restore the tissue proteins.
Vitamins C and E have an antioxidant and antiinflammatory activity.
When the composition of the invention contains one or more of the actives listed above, it also has an antioxidant and anti-inflammatory effect, beside the cure and prevention activity for the intestinal diseases described above.
The composition formulated as a gel, cream, or rectal suppository will have to be externally applied, at the perianal region, twice daily or more often, until complete recovery; or, by means of a special applicator, into the internal rectal area twice daily or more often, until complete recovery.
EXAMPLES
Some examples of composition and formulation of the invention are set forth below.
Example 1
Figure imgf000009_0001
Excipients: diethylamine, carbomers, macrogol cetostearyl ether, cocoyl caprylocaprate, isopropyl alcohol, liquid paraffin, propylen glycol, filtered water .
Example 2
30 ml Enema
Figure imgf000009_0002

Claims

1. A composition comprising sucralphate and mesalazine in an amount ranging from 0,1 to 99% by weight, and from 99% by weight to 0.1% by weight, respectively, formulated, together with pharmacologically acceptable excipients, as a gel, cream, enema, or rectal suppository for an internal or perianal application.
2. The composition according to claim 1, comprising from 0.5 to 50% by weight, preferably from 1 to 10% by weight, more preferably from 1 to 8% by weight sucralphate, and from 0.01 to 20% by weight, more preferably from 0.05% to 10% by weight, still more preferably from 0.5%. to 5% by weight, mesalazine, and formulated as a gel, cream, enema, or rectal suppository.
3. The composition according to claim 1 or 2, further comprising one or more actives selected from the group consisting of: grapefruit seed extract, methyl sulfonyl methane (MSM) , lactic acid, glycine, vitamins .
4. The composition according to claim 3, wherein each of said actives, when present in the composition, are included in an amount ranging from 0.01 to 10% by weight, preferably from 0.5 to 8% by weight, more preferably from 1 to 5% by weight.
5. The composition according to any claim 1 to 5, wherein said pharmacologically acceptable excipients are selected from the group consisting of: glycerine, Vaseline, anhydrous lanolin, shark liver oil, sodium saccharinate, menthol, sweet almond oil, sorbitol, sodium benzoate, anoxid SBN, vanilla essential oil, aerosol, parabens in phenoxyethanol, sodium methyl p- oxybenzoate, sodium propyl p-oxybenzoate, diethylamine, carbomers, macrogol cetostearyl ether, cocoyl caprylocaprate, isopropyl alcohol, propylen glycol, liquid paraffin, xanthan gum, carboxymetabisulfite, sodium edetate, sodium benzoate, potassium metabisulfite, potassium acetate, and mixtures of two or more components thereof.
6. The composition according to any claim 1 to 5, formulated as a rectal gel comprising, in 5Og: 2.5g sucralphate, 0.5g mesalazine, and pharmacologically acceptable excipients.
7. The composition according to any claim 1 to 6, formulated as a rectal enema comprising, in 100 ml: 2g sucralphate, 0.5g mesalazine, 0.075g xanthan gum, 0.0225g carboxypolimethylene, 0.03g sodium edetate, 0, 14g potassium metabisulfite, 0,123g potassium acetate, filtered water quantum satis.
8. The composition according to any claim 1 to 7 for medical use.
9. The composition according to claim 8, for use in the treatment of diseases selected from the group consisting of: actinic proctitis, diversion proctitis, aphthoid lesions of the rectum caused by avitaminosis or viruses, rhagades, fistulizing lesions, solitary ulcer of the rectum, haemorrhoids, anal itching.
10. The composition according to claim 9, for use in the treatment of rectal lesions caused by endoscopic dilatation, lesions of the rectum caused by radiotherapy or chemotherapy.
PCT/IT2008/000639 2007-10-11 2008-10-08 Pharmaceutical composition comprising sucralphate and mesalazine WO2009047826A2 (en)

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IT001965A ITMI20071965A1 (en) 2007-10-11 2007-10-11 PHARMACEUTICAL COMPOSITION INCLUDING SUCRALFATE AND MESALAZINE
ITMI2007A001965 2007-10-11

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2449316A1 (en) * 2012-09-19 2014-03-19 José HERNÁNDEZ MONDÉJAR Physiological solution for internal anal canal hygiene (Machine-translation by Google Translate, not legally binding)
CN104524300A (en) * 2015-01-08 2015-04-22 李宏 Medicament for improving myocardial ischemia injury caused by chemotherapy and preparation method
CN105343687A (en) * 2015-11-13 2016-02-24 张雯 Traditional Chinese medicine for treating rectitis and colitis and its preparation method
CN108853293A (en) * 2018-09-25 2018-11-23 江西中医药大学 Treat compounding essential oil of hemorrhoid and preparation method thereof and application method

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WO2002022120A1 (en) * 2000-09-15 2002-03-21 Medical Merchandising, Inc. Pain reliever and method of use
WO2005115075A2 (en) * 2004-05-27 2005-12-08 Antibe Therapeutics Inc. Salt of 4- or 5- aminosalicylic acid
US20070167416A1 (en) * 2006-11-03 2007-07-19 Johnson Lorin K Formulations and uses of 2-hydroxy-5-phenylazobenzoic acid derivatives

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2449316A1 (en) * 2012-09-19 2014-03-19 José HERNÁNDEZ MONDÉJAR Physiological solution for internal anal canal hygiene (Machine-translation by Google Translate, not legally binding)
CN104524300A (en) * 2015-01-08 2015-04-22 李宏 Medicament for improving myocardial ischemia injury caused by chemotherapy and preparation method
CN105343687A (en) * 2015-11-13 2016-02-24 张雯 Traditional Chinese medicine for treating rectitis and colitis and its preparation method
CN108853293A (en) * 2018-09-25 2018-11-23 江西中医药大学 Treat compounding essential oil of hemorrhoid and preparation method thereof and application method
CN108853293B (en) * 2018-09-25 2021-07-23 江西中医药大学 Compound essential oil for treating hemorrhoids and preparation method and use method thereof

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