EP4096629A1 - Butyric acid salt-based composition for rectal application for the treatment of proctology disorders - Google Patents

Butyric acid salt-based composition for rectal application for the treatment of proctology disorders

Info

Publication number
EP4096629A1
EP4096629A1 EP21708364.1A EP21708364A EP4096629A1 EP 4096629 A1 EP4096629 A1 EP 4096629A1 EP 21708364 A EP21708364 A EP 21708364A EP 4096629 A1 EP4096629 A1 EP 4096629A1
Authority
EP
European Patent Office
Prior art keywords
butyrate
sodium hyaluronate
polymer compound
compositions
composition according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP21708364.1A
Other languages
German (de)
French (fr)
Inventor
Cristian Salvatore
Nicola Danzo
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Caprika Srl
Original Assignee
Caprika Srl
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Caprika Srl filed Critical Caprika Srl
Publication of EP4096629A1 publication Critical patent/EP4096629A1/en
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • 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

  • the present invention concerns a butyric acid salt-based composition for rectal application for the treatment of proctology disorders, including haemorrhoidal syndrome, to which the description will refer without loss of generality.
  • Haemorrhoidal syndrome is one of the most frequent disorders in the gastroenterological field. It has been calculated that in the western countries the prevalence is around 10%, occurring most often between the ages of 45 and 65, with equal frequency in men and women. Very often haemorrhoidal syndrome, and anorectal diseases in general, are the consequence of chronic constipation. The latter represents one, if not the most important, risk factor for the development of pathologies like haemorrhoid congestion, rectal prolapse, diverticulitis and complications thereof.
  • the choice of the most suitable treatment to solve the problem of haemorrhoidal syndrome depends largely on the stage of the disease. For preventive purposes, it is possible to intervene by modifying dietary and hygiene habits and lifestyle in general, and in the initial phases of the disease the application of ointments and creams for local use can be extremely useful. If, on the other hand, the disease has progressed to a more advanced stage, the use of topical medicaments may not be sufficient and more targeted outpatient treatments will be necessary such as, for example, cryotherapy or laser therapy, or even surgery. As is known, the more advanced the stage of the disease, the greater the pain caused.
  • the inventors of the present invention have produced a composition for rectal use based on a butyric acid salt able to meet the above need and applicable both in the form of a micro enema and in the form of a rectal cream.
  • the subject of the present invention is a water-based composition for use in the rectal treatment of proctological disorders characterised in that it comprises sodium hyaluronate butyrate and a polymer compound belonging to the polysiloxane family and having a nominal viscosity ranging from 200 to 500 mm 2 /s; the weight ratio between sodium hyaluronate butyrate and the polymer compound ranges from 0.01 to 0.1.
  • the nominal viscosity of the polymer compound belonging to the polysiloxane family is an important characteristic for the invention, since it gives the composition a viscosizing effect essential for its efficacy.
  • the complex consisting of said sodium hyaluronate butyrate and said polymer compound is present in the composition in a quantity ranging from 1% to 20% by weight with respect to the quantity of water.
  • said polymer compound is a polyalkylsiloxane, more preferably a polydimethylsiloxane.
  • the weight ratio between sodium hyaluronate butyrate and the polymer compound ranges from 0.01 to 0.05.
  • the complex consisting of sodium hyaluronate butyrate and polysiloxanes is present in a quantity ranging from 1% to 10% by weight with respect to the quantity of water.
  • the presence of the polysiloxane is essential for providing a mechanical barrier at proctological level which has the purpose of protecting the mucosa from external insults, favouring restoration of the homeostasis of the surrounding environment. Furthermore, once the water has evaporated, the polysiloxane allows the formation of a film able to retain the functional substances. In other words, the polysiloxane helps the sodium hyaluronate butyrate to persist on the mucosa and is in turn useful for restoring the compromised mucosa. Lastly, the polysiloxane has a viscosizing action such as to give the composition the correct consistency. In fact, like all preparations applied rectally, also the compositions subject of the present invention must have a consistency that is not too liquid otherwise they tend to seep out without coming into contact with the mucosa.
  • a further subject of the present invention is a micro-enema comprising the composition subject of the present invention.
  • a further subject of the present invention is a cream for rectal use comprising the composition subject of the present invention.
  • Tables I and II show the compositions in % by weight of the above-mentioned formulations.
  • the preservative used is marketed under the name ISOCIDE® BAS.
  • the dimethicone used is marketed under the name Acesil® 350.
  • the sodium hyaluronate butyrate used is marketed under the name ITHABUT®. A procedure is reported below for preparation of the twelve compositions described above.
  • a uniform emulsion was produced by placing the emulsifying agents, the thickening agents and an aliquot of water in a mixer (Laborall Kyro 350) or in a fuser (Laborall Antares Fuser) according to whether the compositions are intended for use in the form of cream or in the form of a micro-enema respectively.
  • the system was set to quick stirring, leaving the mixture to emulsify for 20-25 minutes until obtaining a uniform emulsion.
  • the sodium hyaluronate butyrate was cold-solubilized in a remaining aliquot of water until forming a transparent and uniform gel to which the dimethicone was added.
  • the solution with sodium hyaluronate butyrate and dimethicone was combined with the emulsion previously produced, pouring it into the mixer (compositions usable in the form of cream) or into the fuser (compositions usable in the form of micro-enema) .
  • the system thus obtained was left under stirring for 20 minutes.
  • Two of the comparison compositions are compositions useful for administration with micro-enemas and differ from the composition 1 respectively due to the presence of the sodium hyaluronate instead of sodium hyaluronate butyrate and due to the absence of the dimethicone.
  • compositions la and lb have a viscosity of 630 and 600 mm 2 /s respectively .
  • Two of the comparison compositions (7a, 7b) are compositions useful for administration in the form of cream and differ from composition 7 respectively due to the presence of the sodium hyaluronate instead of the sodium hyaluronate butyrate and due to the absence of the dimethicone.
  • compositions 7a and 7b have a viscosity of 650 and 620 mm 2 /s respectively.
  • compositions 1, 7, la, lb, 7a and 7b were tested to verify their efficacy in the treatment of haemorrhoidal syndrome.
  • the study concerned a daily administration of each of the above compositions (1, 7, la, lb, 7a and 7b) to a respective group of patients for two weeks.
  • the patients recruited were all over the age of 18 and had haemorrhoidal syndrome and/or anorectal diseases.
  • each group of patients was composed of ten men and ten women. Of these, nine patients were affected by irritable bowel syndrome (IBS) and eleven patients were affected by primary constipation.
  • IBS irritable bowel syndrome
  • compositions were verified in terms of clinical evaluation of the dominant symptoms such as: pain and burning sensation, bleeding, feeling of heaviness in the rectal area, secretions of mucous and itching.
  • the evaluation was carried out by means of scores from 1 to 10 in terms of increasing intensity.
  • Tables III and IV report the mean evaluations of the patients before and after the treatment with compositions 1 and 7 of the present invention and with the comparison compositions.
  • compositions subject of the present invention have a high efficacy able to abate the symptoms connected with haemorrhoidal syndrome.
  • compositions 1 and 7 respectively highlights the importance of the presence of the polysiloxane polymer in the composition.
  • the importance of the presence of this polymer derives both from the viscosizing action produced, able to give the composition the correct consistency to guarantee the permanent contact thereof with the mucosa, and from the formation of a film able to retain the functional substances and, therefore, help the sodium hyaluronate butyrate to persist on the mucosa to aid the healing thereof.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Vascular Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

A water-based composition for use in the rectal treatment of proctological disorders comprising sodium hyaluronate butyrate and a polymer compound belonging to the polysiloxane family and having a nominal viscosity ranging from 200 to 500 mm2/s. The weight ratio between sodium hyaluronate butyrate and the polymer compound ranges from 0.01 to 0.1.

Description

"BUTYRIC ACID SALT-BASED COMPOSITION FOR RECTAL APPLICATION FOR THE TREATMENT OF PROCTOLOGY DISORDERS"
CROSS-REFERENCE TO RELATED APPLICATIONS
This patent application claims priority from Italian patent application no. 102020000001831 filed on 30/01/2020, the entire disclosure of which is incorporated herein by reference.
TECHNICAL FIELD
The present invention concerns a butyric acid salt-based composition for rectal application for the treatment of proctology disorders, including haemorrhoidal syndrome, to which the description will refer without loss of generality.
BACKGROUND ART
Haemorrhoidal syndrome is one of the most frequent disorders in the gastroenterological field. It has been calculated that in the western countries the prevalence is around 10%, occurring most often between the ages of 45 and 65, with equal frequency in men and women. Very often haemorrhoidal syndrome, and anorectal diseases in general, are the consequence of chronic constipation. The latter represents one, if not the most important, risk factor for the development of pathologies like haemorrhoid congestion, rectal prolapse, diverticulitis and complications thereof.
The choice of the most suitable treatment to solve the problem of haemorrhoidal syndrome depends largely on the stage of the disease. For preventive purposes, it is possible to intervene by modifying dietary and hygiene habits and lifestyle in general, and in the initial phases of the disease the application of ointments and creams for local use can be extremely useful. If, on the other hand, the disease has progressed to a more advanced stage, the use of topical medicaments may not be sufficient and more targeted outpatient treatments will be necessary such as, for example, cryotherapy or laser therapy, or even surgery. As is known, the more advanced the stage of the disease, the greater the pain caused.
From the above description, in order to avoid invasive treatments and prevent the pain becoming acute, prompt effective intervention with ointments or creams is important.
In this regard, the need is felt to make available to patients compositions with increasingly effective therapeutic action and without side effects (for example cortisone-based compositions are toxic and give rise to problems of burning sensation or sensitization) .
The inventors of the present invention have produced a composition for rectal use based on a butyric acid salt able to meet the above need and applicable both in the form of a micro enema and in the form of a rectal cream.
DISCLOSURE OF INVENTION
The subject of the present invention is a water-based composition for use in the rectal treatment of proctological disorders characterised in that it comprises sodium hyaluronate butyrate and a polymer compound belonging to the polysiloxane family and having a nominal viscosity ranging from 200 to 500 mm2/s; the weight ratio between sodium hyaluronate butyrate and the polymer compound ranges from 0.01 to 0.1.
The nominal viscosity of the polymer compound belonging to the polysiloxane family is an important characteristic for the invention, since it gives the composition a viscosizing effect essential for its efficacy.
Preferably, the complex consisting of said sodium hyaluronate butyrate and said polymer compound is present in the composition in a quantity ranging from 1% to 20% by weight with respect to the quantity of water. Preferably, said polymer compound is a polyalkylsiloxane, more preferably a polydimethylsiloxane.
Preferably, the weight ratio between sodium hyaluronate butyrate and the polymer compound ranges from 0.01 to 0.05.
Preferably, the complex consisting of sodium hyaluronate butyrate and polysiloxanes is present in a quantity ranging from 1% to 10% by weight with respect to the quantity of water.
The presence of the polysiloxane is essential for providing a mechanical barrier at proctological level which has the purpose of protecting the mucosa from external insults, favouring restoration of the homeostasis of the surrounding environment. Furthermore, once the water has evaporated, the polysiloxane allows the formation of a film able to retain the functional substances. In other words, the polysiloxane helps the sodium hyaluronate butyrate to persist on the mucosa and is in turn useful for restoring the compromised mucosa. Lastly, the polysiloxane has a viscosizing action such as to give the composition the correct consistency. In fact, like all preparations applied rectally, also the compositions subject of the present invention must have a consistency that is not too liquid otherwise they tend to seep out without coming into contact with the mucosa.
A further subject of the present invention is a micro-enema comprising the composition subject of the present invention.
A further subject of the present invention is a cream for rectal use comprising the composition subject of the present invention.
BEST MODE FOR CARRYING OUT THE INVENTION
Below, illustrative non-limiting examples are described for a better understanding of the present invention.
Six formulations (1 - 6) were prepared useful for administration with micro-enemas and six formulations (7 - 12) for application in the form of cream.
Tables I and II show the compositions in % by weight of the above-mentioned formulations.
Table I Table
The preservative used is marketed under the name ISOCIDE® BAS.
The dimethicone used is marketed under the name Acesil® 350.
The sodium hyaluronate butyrate used is marketed under the name ITHABUT®. A procedure is reported below for preparation of the twelve compositions described above.
A uniform emulsion was produced by placing the emulsifying agents, the thickening agents and an aliquot of water in a mixer (Laborall Kyro 350) or in a fuser (Laborall Antares Fuser) according to whether the compositions are intended for use in the form of cream or in the form of a micro-enema respectively.
In both the mixer and the fuser, the system was set to quick stirring, leaving the mixture to emulsify for 20-25 minutes until obtaining a uniform emulsion.
Separately, in a steel dissolution apparatus the sodium hyaluronate butyrate was cold-solubilized in a remaining aliquot of water until forming a transparent and uniform gel to which the dimethicone was added.
At this point, the solution with sodium hyaluronate butyrate and dimethicone was combined with the emulsion previously produced, pouring it into the mixer (compositions usable in the form of cream) or into the fuser (compositions usable in the form of micro-enema) . The system thus obtained was left under stirring for 20 minutes.
To better verify the efficacy of the compositions subject of the invention, four comparison compositions were produced.
Two of the comparison compositions (la, lb) are compositions useful for administration with micro-enemas and differ from the composition 1 respectively due to the presence of the sodium hyaluronate instead of sodium hyaluronate butyrate and due to the absence of the dimethicone.
The compositions la and lb have a viscosity of 630 and 600 mm2/s respectively . Two of the comparison compositions (7a, 7b) are compositions useful for administration in the form of cream and differ from composition 7 respectively due to the presence of the sodium hyaluronate instead of the sodium hyaluronate butyrate and due to the absence of the dimethicone.
The compositions 7a and 7b have a viscosity of 650 and 620 mm2/s respectively.
The compositions 1, 7, la, lb, 7a and 7b were tested to verify their efficacy in the treatment of haemorrhoidal syndrome.
The study concerned a daily administration of each of the above compositions (1, 7, la, lb, 7a and 7b) to a respective group of patients for two weeks. The patients recruited were all over the age of 18 and had haemorrhoidal syndrome and/or anorectal diseases.
In particular, each group of patients was composed of ten men and ten women. Of these, nine patients were affected by irritable bowel syndrome (IBS) and eleven patients were affected by primary constipation.
The efficacy of the compositions was verified in terms of clinical evaluation of the dominant symptoms such as: pain and burning sensation, bleeding, feeling of heaviness in the rectal area, secretions of mucous and itching.
The evaluation was carried out by means of scores from 1 to 10 in terms of increasing intensity.
Tables III and IV report the mean evaluations of the patients before and after the treatment with compositions 1 and 7 of the present invention and with the comparison compositions.
Table III
Table IV
From Tables III and IV it is evident that the compositions subject of the present invention have a high efficacy able to abate the symptoms connected with haemorrhoidal syndrome.
It is important to note that the simultaneous presence of the sodium hyaluronate butyrate and the polymer belonging to the polysiloxane family guarantees better results than the comparison compositions. In particular, it should be underlined that comparison of the compositions 1 and 7 respectively with compositions la and 7a shows greater efficacy of the sodium hyaluronate butyrate compared to the sodium hyaluronate. To date, the properties of sodium hyaluronate butyrate for the treatment of proctological disorders were not known.
Lastly, comparison of compositions 1 and 7 with compositions lb and 7b respectively highlights the importance of the presence of the polysiloxane polymer in the composition. In particular, the importance of the presence of this polymer derives both from the viscosizing action produced, able to give the composition the correct consistency to guarantee the permanent contact thereof with the mucosa, and from the formation of a film able to retain the functional substances and, therefore, help the sodium hyaluronate butyrate to persist on the mucosa to aid the healing thereof.

Claims

1. A water-based composition for use in the rectal treatment of proctological disorders characterized in that it comprises sodium hyaluronate butyrate and a polymer compound belonging to the polysiloxane family and having a nominal viscosity ranging from 200 to 500 mm2/s; the weight ratio between sodium hyaluronate butyrate and the polymer compound ranging from 0.01 to 0.1.
2. The composition according to claim 1, characterized in that the complex consisting of said sodium hyaluronate butyrate and of said polymer compound is present in a quantity ranging from 1% to 20% by weight relative to the quantity of water.
3. The composition according to claim 1 or 2, characterized in that said polymer compound is a polyalkylsiloxane.
4. The composition according to claim 3, characterized in that said polymer compound is a polydimethylsiloxane.
5. The composition according to one of the preceding claims, characterized in that the weight ratio between sodium hyaluronate butyrate and the polymer compound ranges from 0.01 to 0.05.
6. The composition according to one of the preceding claims, characterized in that the complex consisting of sodium hyaluronate butyrate and polysiloxanes is present in a quantity ranging from 1% to 10% by weight relative to the quantity of water.
7. A micro-enema characterized in that it comprises the composition according to one of the preceding claims.
8. A rectal use cream characterized in that it comprises the composition according to one of the claims from 1 to 6.
EP21708364.1A 2020-01-30 2021-01-28 Butyric acid salt-based composition for rectal application for the treatment of proctology disorders Pending EP4096629A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT102020000001831A IT202000001831A1 (en) 2020-01-30 2020-01-30 COMPOSITION FOR RECTAL APPLICATION BASED ON BUTYRIC ACID SALT FOR THE TREATMENT OF PROCTOLOGICAL PATHOLOGIES
PCT/IB2021/050659 WO2021152492A1 (en) 2020-01-30 2021-01-28 Butyric acid salt-based composition for rectal application for the treatment of proctology disorders

Publications (1)

Publication Number Publication Date
EP4096629A1 true EP4096629A1 (en) 2022-12-07

Family

ID=70480457

Family Applications (1)

Application Number Title Priority Date Filing Date
EP21708364.1A Pending EP4096629A1 (en) 2020-01-30 2021-01-28 Butyric acid salt-based composition for rectal application for the treatment of proctology disorders

Country Status (3)

Country Link
EP (1) EP4096629A1 (en)
IT (1) IT202000001831A1 (en)
WO (1) WO2021152492A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023170597A1 (en) * 2022-03-08 2023-09-14 Sila S.P.A. Topical composition for treating injuries or cutaneous inflammatory states or proctological pathologies

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4341165C1 (en) * 1993-12-02 1995-04-20 Upmeyer Hans Juergen Use of Dimeticon to treat constipation
ITMI20072237A1 (en) * 2007-11-27 2009-05-28 Sigea Srl MIXED BUTIRRIC-FORMAL ESTERS OF ACID POLYSACCHARIDES, THEIR PREPARATION AND USE AS DERMOCOSMETICS
US20100080768A1 (en) * 2008-09-26 2010-04-01 Mcgraw Thomas L Compositions and Methods for the Treatment of Inflammatory Dermatosis and Other Pathological Conditions of the Skin
KR20110035312A (en) * 2009-09-30 2011-04-06 일동제약주식회사 Effective treatment for hemorrhoids using hyaluronic acid
PT3245233T (en) * 2015-01-13 2019-01-16 Bmg Pharma S P A Process in water for the preparation of butyric esters of hyaluronic acid sodium salt
WO2020141986A1 (en) * 2018-12-30 2020-07-09 Jamjoom Pharmaceuticals Factory Company Limited Silicone gel composition containing hyaluronic acid and/or its salt for prevention and repair of skin scars

Also Published As

Publication number Publication date
IT202000001831A1 (en) 2021-07-30
WO2021152492A1 (en) 2021-08-05

Similar Documents

Publication Publication Date Title
Kirchrath et al. Cyclooxygenase-2 inhibition and side-effects of non-steroidal anti-inflammatory drugs in the gastrointestinal tract.
Tefekli et al. Peyronie's disease in men under age 40: characteristics and outcome
WO1996014828A1 (en) Hemorrhoidal compositions and method of use
JPH09504037A (en) Nitric oxide donors and methods for treating anal disorders
JP2001507020A (en) Pharmaceutical composition for treating fecal incontinence and pruritus ani
EP4096629A1 (en) Butyric acid salt-based composition for rectal application for the treatment of proctology disorders
Drusin et al. The role of surgery in primary syphilis of the anus.
JP2007508371A (en) Osteoarthritis therapeutic composition containing apigenin as cartilage regenerative agent
JP2004519451A (en) Pharmaceutical composition for treatment of phimosis with topical corticosteroid
US20130108724A1 (en) Topical therapeautic composition and palliative treatment method
PL198790B1 (en) Mesoprogestins for the treatment and prevention of benign hormone dependent gynecological disorders
RU2293561C1 (en) Method for predicting acute appendicitis in pregnant women
Collier SOME CASES OF HALLUX RIGIDUS: THEIR SYMPTOMS, PATHOLOGY, AND TREATMENT.
Lichtenstein Rectal stricture: A clinical analysis of 58 cases, with observations on 154 Frei-positive cases of lymphogranuloma inguinale
ANSARI et al. A Comparative Study of Topical Diltiazem (2%) with Topical Glyceryl Trinitrate (0.2%) as a Conservative Treatment for Anal Fissure.
RU2705794C1 (en) Combined soft dosage form for treating haemorrhoid diseases
CN106074615B (en) Gastrointestinal hemostasis defoaming bacteriostatic agent and preparation method thereof
Nasrat et al. The biology of combined colon clear and blood-let out cupping therapy in female health
Bancroft et al. The treatment of actinomycosis with thymol
Ruiz Ibán et al. Adhesive Capsulitis
Londhe et al. Study on the Anti-lithogenic effect of Tablet Bigol and Shashwat Ghrita in the management of Cholelithiasis (Pittashmari)
Allan Congenital diverticula in the greater curvature of the fundus of the stomach
Münnich et al. Single-Day Topical Treatment of Vaginal Candidosis: An Open Evaluation of Terconazole 240-mg Vaginal Suppositories versus Isoconazole Tablets 600 mg
Bloomer et al. SAT-192 Eletriptan (RelpaxaTm) Causing False Positive Elevations in Urinary Metanephrine
HUMISTON IMPORTANCE OF EARLY RECOGNITION OF CANCER OF THE UTERUS.

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: UNKNOWN

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20220723

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)
P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230608

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: EXAMINATION IS IN PROGRESS

17Q First examination report despatched

Effective date: 20240826