WO2000053183A1 - Medicament against dysmenorrhoea and premenstrual syndrome - Google Patents
Medicament against dysmenorrhoea and premenstrual syndrome Download PDFInfo
- Publication number
- WO2000053183A1 WO2000053183A1 PCT/US2000/003782 US0003782W WO0053183A1 WO 2000053183 A1 WO2000053183 A1 WO 2000053183A1 US 0003782 W US0003782 W US 0003782W WO 0053183 A1 WO0053183 A1 WO 0053183A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- woman
- local anesthetic
- administering
- dysmenorrhoea
- reducing
- Prior art date
Links
Classifications
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
Definitions
- the present invention relates to the use of a local anesthetic for the manufacture of a medicament for use against dysmenorrhoea and premenstrual syndrome .
- Peritoneal fluid macrophages in women with endometriosis may also have an increased capacity to resist apoptosis (programmed cell death) and to continue to survive which might be crucial for the fertility. Further phagocytosis of spermatozoa has been found to be increased during incubations for 24 hours in vitro with the peritoneal fluid from patients with endometriosis . Infertility or sub-fertility could be a problem for people afflicted therewith.
- IVF in vitro fertilization
- the basis of the IVF treatment is as follows:
- Stimulation of ovulation Daily hormonal injections, ultrasound examinations and blood samples; Oocyte retrieval: Ultrasound guided ovarian punctures performed vaginally in local anesthesia;
- In vitro fertilization Incubation of oocytes and the selected population of spermatozoa in a cell incubator.
- IVF treatment is an expensive method that for some couples initiates complicated psychological side effects.
- the technical and artificial way of trying to become pregnant has the disadvantages for the couple going through the treatment which may adversely affect the relationship.
- the present invention is an alternative method to the IVF treatment for increasing fertility and for reducing dysmenorrhoea and premenstrual syndrome of women. It has been found by in vitro studies that phagocytosis of spermatozoa is reduced by lidocaine. It is suggested that this effect of lidocaine is due to stabilization of the cell membrane by prohibiting the increase of Na + permeability and by probably interfering with ATP in the cell membrane. The cost for this treatment will be approximately 10% of the IVF treatment, e.g., 2,500 SEK per menstrual cycle. There is no technical fertilization process that can cause psychological side effects. This treatment can be tried in patients with endometriosis and/or slight mechanical cause of infertility. It can be carried out while waiting for IVF and does not affect the possibility of successful later IVF treatment.
- lidocaine So far no treatment of infertility with lidocaine is reported in the literature. However, other pharmaceutical effects of lidocaine are known, e.g., as in EP 507 160, which discloses an external preparation for application to the skin containing; lidocaine which comprises a drug-retaining layer placed on a support. The preparation should be used for treatment of herpes zoster neuralgia and postherpetic neuralgia.
- the present invention relates to a local anesthetic that may be used for the manufacture of a medicament for use against dysmenorrhoea and premenstrual syndrome and for increasing fertility.
- a pharmaceutical composition may also be used that comprises a pharmaceutically effective dose of a local anesthetic together with a pharmaceutically acceptable excipient.
- the invention also relates to a process for reducing dysmenorrhoea and premenstrual syndrome symptoms in a woman with said pharmaceutical composition.
- endometr relates to endometriosis and end-prob relates to probable endometriosis .
- Fig. 1 is a schematic illustration showing the number of free spermatozoa shown for each day of incubation: with cell medium (A, control) , with cell medium and lidocaine (B) , with peritoneal fluid (C, control) and with peritoneal fluid and lidocaine (D) ;
- Fig. 2 is a schematic illustration showing the number of progressively moving spermatozoa shown for each day of incubation: with cell medium (A, control), with cell medium and lidocaine (B) , with peritoneal fluid (C, control) and with peritoneal fluid and lidocaine (D) ;
- Fig. 3 is a schematic illustration showing the number of non progressively but moving spermatozoa shown for each day of incubation: with cell medium (A, control), with cell medium and lidocaine (B) , with peritoneal fluid (C, control) and with peritoneal fluid and lidocaine (D) ;
- Fig. 4 is a schematic illustration showing the number of alive but stationary spermatozoa shown for each day of incubation: with cell medium (A, control), with cell medium and lidocaine (B) , with peritoneal fluid (C, control) and with peritoneal fluid and lidocaine (D) ; and
- Fig. 5 is a schematic illustration showing the number of dead spermatozoa shown for each day of incubation: with cell medium (A, control) , with cell medium and lidocaine (B) , with peritoneal fluid (C, control) and with peritoneal fluid and lidocaine (D) .
- a local anesthetic for the manufacture of a medicament for use against infertility or for increasing fertility.
- the local anesthetic may be selected from any substance that has a local anesthetic effect.
- lidocaine (2- (dicthylammo) -N- (2 , 6- dimethylphenyl) acetamide)
- mepivacame N-(2,6- dimethylphenyl) -l-methyl-2-p ⁇ per ⁇ d ⁇ necarboxam ⁇ de
- pnlocaine N- (2-methylphenyl) -2- (propylarr ⁇ no) propanamide
- ropivacame (S) -N- (2 , 6-d ⁇ methylphenyl) -l-propy-2- pipendmecarboxamide)
- Other local anesthetics could also be used.
- lidocaine is used.
- Another feature of the present invention is a pharmaceutical composition
- a pharmaceutical composition comprising a pharmaceutically effective concentration of a local anesthetic together with a pharmaceutically acceptable excipient.
- the concentration is one that has an effect on infertility of a woman or one that increases the fertility of a woman.
- the dose and concentration may be decided by the physician.
- the concentration of the effective substance is at least 5 ⁇ g/ml .
- One may use 100-2000 ⁇ g in 1-20 ml, preferably about 118 ⁇ g .
- the dose that is administrated is at least 100 ⁇ g and preferably about 1000 ⁇ g .
- the composition is preferably administered in the peritoneal cavity, preferably by pertubation.
- the active substance or compound may be mixed with excipients which are pharmaceutically acceptable and compatible with the active ingredient and in amounts suitable for use in the therapeutic methods described herein.
- the composition can contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents and the like which enhance the effectiveness of the active ingredient .
- composition of the present invention may include pharmaceutically acceptable salts of the components herein.
- Pharmaceutically acceptable salts include the acid addition salts that are formed with inorganic acid such as, for example, hydrochloric or phosphoric acids, or such organic acids as acetic, tartaric and mandelic acid.
- Physiologically tolerable carriers may also be used.
- Exemplary of liquid carriers are sterile aqueous solutions that contain no materials in addition to the active ingredients and water or contain a buffer such as sodium phosphate at physiological pH value, physiological saline or both, such as phosphate-buffered saline.
- aqueous carriers may contain more than one buffer salt, as well as salts such as sodium and potassium chlorides, dextrose, propylene glycol , polyethylene glycol and other solutes .
- the composition may also comprise hyaluronan which is a viscous substance, e.g., in gel formate.
- Hyaluronan gives a slow release of the active substance which is preferable as conception may take place up to 24 hours after ovulation and the treatment according to the present invention.
- Another advantage is that hyaluronan has a stimulating effect on the sperms.
- the present invention also embraces a process for treating infertility in a woman with a pharmaceutical composition according to the present invention and may be characterized in that the pharmaceutical composition is inserted by pertubation.
- the present invention especially relates to a cosmetic or a non-therapeutic method against infertility or for increasing fertility wherein: a) ovulation is diagnosed; and b) a treatment with a local anesthetic is performed when ovulation is expected according to step a) .
- the treatment is preferably performed by pertubation.
- the steps are as follows:
- Spontaneous ovulation Primary treatment during normal menstrual cycle. Stimulation only in anovulatory patients and primary with Clomifen (tablets) which is easy and inexpensive. One blood sample is needed post-ovulatory to confirm that there has been an ovulation during the treated cycle.
- LH (luteinizing hormone) test The LH-surge 24-36 hours prior to ovulation is diagnosed by self test at home of urine sample.
- Lidocaine has been used for many years without any reports of adverse effects during pregnancy as has also been shown in an animal study and should therefore be possible to use for treatment of infertility in the endometriotic patient .
- Example 1 Reduction of phagocytosis of spermatozoa in PF (peritoneal fluid) from women with endometriosis.
- the patients were divided into three different groups.
- the control cases had laparoscopic findings considered as normal with anatomically normal uterus and fallopian tubes.
- the diagnose was laparoscopic in 8 patients and anamnestic probable endometriosis in 3 patients but who had not yet developed any endometriotic implants that could be seen at the laparoscopy.
- the sperm donor was a healthy 38 year old male with normal fertility with an continence period of 2-3 days before each sperm sample.
- the sperm samples were prepared by the swim up technique to select the optimal population.
- peritoneal fluid in the Douglas' pouch was aspirated by a suction unit through a Teflon catheter (diameter 1.7 mm, Optinova, Godby, Finland) and mixed with 10 IU of Heparin/ml in a Teflon bottle and immediately taken care of .
- the amount of peritoneal fluid were determined by weighing on an electric balance.
- Teflon was the material of choice for collecting the PF due to its low adhesion of mammalian cells. Heparin was used as anticoagulant to prevent the leukocytes from aggregating. Previously citrate has been used which in the sperm incubation had adverse effects on sperm viability. All samples were taken after permissions from the patients and the sampling procedure was approved by the Ethical Committee, Faculty of Medicine, Uppsala University, Sweden.
- Teflon vials were used for all incubations that were done in a humid cell incubator as follows: a) Cell medium (1 ml) , spermatozoa (10 6 in 1 ml cell medium) and 0 , 1 ml NaCl; b) Cell medium (1 ml) , spermatozoa (10 6 in 1 ml cell medium) and 0 , 1 ml lidocaine 10 mg/ml (Xylocain, ASTRA) ; c) Spermatozoa (10 6 in 1 ml cell medium) , peritoneal fluid (1 ml) and 0 , 1 ml NaCl; and d) Spermatozoa (10° in 1 ml cell medium) , 0,1 ml lidocaine (10 mg/ml) and peritoneal fluid (1 ml) .
- spermatozoa Number of spermatozoa that are stationary and alive; and Number of dead spermatozoa. Also the percentage of viable peritoneal leukocytes were noted daily with the use of Trypan blue. The main finding was that there were statistically significantly less phagocytized spermatozoa (p ⁇ 0.02) in the vials when incubated with peritoneal fluid and lidocaine. The spermatozoa were observed caught in large aggregates of leukocytes and some apparently undergoing phagocytosis thus reducing the number of free functioning spermatozoa .
- peritoneal fluid see Fig. 2
- peritoneal fluid and lidocaine there were significantly more free spermatozoa, especially after two days incubations in the endometriosis group (see Fig. 1 and Table II) .
- Fig. 5 and Table II There were more dead spermatozoa in incubations with lidocaine over time in both diagnosis groups (see Fig. 5 and Table II) .
- Hyaluronan concentrations in peritoneal fluid exhibited no indications of ongoing inflammatory process, i.e., confirming all patients being healthy.
- lidocaine c) more in lidocaine d) more free in the lidocaine group
- This investigation includes the impact of lidocaine on sperm survival and effect on the peritoneal leukocyte phagocytosis of spermatozoa in vitro during incubation for five days. This study has included only one donor of spermatozoa to avoid different immunological combinations which would have been uncontrolled factor in the experiments. Also this study follows the sperm survival for up to 5 days whereas previous studies have investigated the sperm survival during a 24 hour period.
- the fimbriae of the fallopian tubes are constantly moistured by peritoneal fluid which in the case of patients with endometriosis reduces the capacity of ovum pick up.
- the leukocytes in the peritoneal fluid of patients with endometriosis are more potent in phagocytizing spermatozoa.
- women with endometriosis can have two factors contributing to their reduced fertility.
- This study has also indicated the possibility of using the effect of lidocaine in order to reduce the phagocytosis of spermatozoa .
- Lignocaine was added to assess the effect on the spermatozoa alone in the cell medium as well as the effect on the phagocytes in the peritoneal fluid. Samples from the incubations were studied daily and the number of viable and dead spermatozoa were counted. The number of free spermatozoa, not adhered to leucocytes, was significantly increased when incubated in human peritoneal fluid supplemented with lignocaine. Thus, lignocaine contributes to increasing the number of free spermatozoa and maintaining the possibility of fertilizing an oocyte .
- the administration of the active substances and compounds may be performed in a variety of ways.
- the active compounds may include, but are not limited to, local anesthetics, physiological saline, Ringer solution, air and fat emulsions.
- a small thin catheter may be inserted in the cervix or the uterine cavity and a small rubber cuff is filled with saline to prevent retrograde leakage.
- the fluid may then be infused through the uterine cavity, 10-20 ml is used which means that the fluid has to flood through the tubes since the uterine cavity contains only 1-2 ml. There should be no pressure used or needed since the passage has to be open through the tubes.
- the fluid has normal room temperature, but can also be of body temperature .
- the procedure with pertubation has empirically turned out to reduce menstrual pain (dysmenorrhoea) and PMS (premenstrual syndrome) .
- This may be due to a local effect of local anesthetics (i.e., lignocaine) reducing the endometrial implants or depressing the hormonal activity in the ovaries.
- the reduced dysmenorrhoea and PMS may be due to a mechanical effect of removing mucous plugs or intra-fallopian minor adhesions around endometrial implants.
- Another factor may be the mechanical effect of the hormonal change due to the improved mechanical flow through the fallopian tubes that could increase the hormonal drainage of peritoneal fluid from the cavity to the uterine cavity.
- the pertubation procedure also dilutes and reduces the hormonal concentration the in the peritoneal fluid and PMS are thought to partly due the hormonal in serum which is related to the level in the peritoneal cavity.
- This unexpected reduction of menstrual pain and the PMS from the patients who have been treated with pertubation is new and not described earlier.
- treatment with lignocaine might be a means of increasing the chances of conception.
- a clinical study is ongoing since February 1998 to evaluate this effect in vivo and if the method can be used as an alternative to assisted fertilization such as IVF (in vitro fertilization) .
- Lignocaine has been used for many years without any reports of adverse effects during pregnancy.
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT00911804T ATE305784T1 (en) | 1997-02-15 | 2000-02-12 | MEDICINE FOR DYSMENORRHEA AND PREMENSTRUAL SYNDROME CONTAINING LIDOCAIN |
EP00911804A EP1158978B1 (en) | 1997-02-15 | 2000-02-12 | Medicament against dysmenorrhoea and premenstrual syndrome comprising lidocaine |
CA002364470A CA2364470A1 (en) | 1997-02-15 | 2000-02-12 | Medicament against dysmenorrhoea and premenstrual syndrome |
DE60022988T DE60022988T2 (en) | 1999-03-10 | 2000-02-12 | MEDICAMENT AGAINST DYSMENORRHOE AND PREMIUM SYNDROME CONTAINING LIDOCAINE |
ES00911804T ES2249250T3 (en) | 1997-02-15 | 2000-02-12 | MEDICATION AGAINST DISMENORREA AND THE PREMENSTRUAL SYNDROME UNDERSTANDING LIDOCAINE. |
AU33637/00A AU774046B2 (en) | 1997-02-15 | 2000-02-12 | Medicament against dysmenorrhoea and premenstrual syndrome |
NO20014361A NO323693B1 (en) | 1997-02-15 | 2001-09-07 | Use of a composition comprising lidocaine together with ± one or more pharmaceutically acceptable excipients for the manufacture of a medicament for the treatment or prevention of dysmenorrhea conditions. |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/800,737 US5977143A (en) | 1997-02-15 | 1997-02-15 | Medicament against infertility which reduces phagocytosis of spermatozoa in women |
US26550299A | 1999-03-10 | 1999-03-10 | |
US09/265,502 | 1999-03-10 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2000053183A1 true WO2000053183A1 (en) | 2000-09-14 |
Family
ID=26951241
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/003782 WO2000053183A1 (en) | 1997-02-15 | 2000-02-12 | Medicament against dysmenorrhoea and premenstrual syndrome |
Country Status (8)
Country | Link |
---|---|
US (2) | US6835388B2 (en) |
EP (1) | EP1158978B1 (en) |
AT (1) | ATE305784T1 (en) |
AU (1) | AU774046B2 (en) |
CA (1) | CA2364470A1 (en) |
ES (1) | ES2249250T3 (en) |
NO (1) | NO323693B1 (en) |
WO (1) | WO2000053183A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017069672A1 (en) * | 2015-10-23 | 2017-04-27 | Isifer Ab | Composition for treatment of infertility in a female subject |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU774046B2 (en) * | 1997-02-15 | 2004-06-17 | Edelstam Inc. | Medicament against dysmenorrhoea and premenstrual syndrome |
US20080182841A1 (en) * | 2001-10-29 | 2008-07-31 | Levine Howard L | Vaginally administered anti-dysrhythmic agents for treating pelvic pain |
US20040142968A1 (en) * | 2003-01-17 | 2004-07-22 | Donald Price | Method and kit for treating lower bowel pain |
US7672794B2 (en) * | 2003-06-24 | 2010-03-02 | Expro Meters, Inc. | System and method for operating a flow process |
US20120065221A1 (en) * | 2009-02-26 | 2012-03-15 | Theraquest Biosciences, Inc. | Extended Release Oral Pharmaceutical Compositions of 3-Hydroxy-N-Methylmorphinan and Method of Use |
US9849102B2 (en) * | 2010-05-19 | 2017-12-26 | Isifer Ab | Treatment for reducing inflammation |
US9440671B2 (en) * | 2012-09-20 | 2016-09-13 | Polaris Industries Inc. | Vehicle |
AU2014374361B9 (en) | 2013-12-31 | 2019-07-04 | Abbott Diabetes Care Inc. | Self-powered analyte sensor and devices using the same |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5534242A (en) * | 1994-05-02 | 1996-07-09 | Henry; Richard A. | Lidocaine-vasoconstrictor aerosol preparation |
WO1998056323A1 (en) * | 1997-06-11 | 1998-12-17 | Umd, Inc. | Device and method for treatment of dysmenorrhea |
WO2004046417A2 (en) | 2002-11-15 | 2004-06-03 | President And Fellows Of Harvard College | Atomic layer deposition using metal amidinates |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3964563A (en) * | 1975-01-29 | 1976-06-22 | Allen Carling D | Wheel-support structure in vehicles |
US4207891A (en) * | 1978-10-10 | 1980-06-17 | Population Research Incorporated | Dispensing instrument with supported balloon |
US4780480A (en) * | 1983-07-14 | 1988-10-25 | Syntex (U.S.A.) Inc. | Aroyl benzofuran and benzothiophene acetic and propionic acids |
AU774046B2 (en) * | 1997-02-15 | 2004-06-17 | Edelstam Inc. | Medicament against dysmenorrhoea and premenstrual syndrome |
US5977143A (en) * | 1997-02-15 | 1999-11-02 | Edelstam; Greta | Medicament against infertility which reduces phagocytosis of spermatozoa in women |
-
2000
- 2000-02-12 AU AU33637/00A patent/AU774046B2/en not_active Expired
- 2000-02-12 CA CA002364470A patent/CA2364470A1/en not_active Abandoned
- 2000-02-12 ES ES00911804T patent/ES2249250T3/en not_active Expired - Lifetime
- 2000-02-12 EP EP00911804A patent/EP1158978B1/en not_active Expired - Lifetime
- 2000-02-12 AT AT00911804T patent/ATE305784T1/en not_active IP Right Cessation
- 2000-02-12 WO PCT/US2000/003782 patent/WO2000053183A1/en active IP Right Grant
-
2001
- 2001-09-07 NO NO20014361A patent/NO323693B1/en not_active IP Right Cessation
-
2002
- 2002-08-02 US US10/211,048 patent/US6835388B2/en not_active Expired - Lifetime
- 2002-08-02 US US10/211,050 patent/US6716446B2/en not_active Expired - Lifetime
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5534242A (en) * | 1994-05-02 | 1996-07-09 | Henry; Richard A. | Lidocaine-vasoconstrictor aerosol preparation |
WO1998056323A1 (en) * | 1997-06-11 | 1998-12-17 | Umd, Inc. | Device and method for treatment of dysmenorrhea |
WO2004046417A2 (en) | 2002-11-15 | 2004-06-03 | President And Fellows Of Harvard College | Atomic layer deposition using metal amidinates |
Non-Patent Citations (6)
Title |
---|
DATABASE MEDLINE ON STN, (BETHESDA, MD, USA),; WALDMAN S.D. ET AL.: "Superior hypogastric plexus block using a single needle and computed tomography guidance: description of a modified technique", XP002908701 * |
HOON KIM ET AL., JOURNAL OF THE ELECTROCHEMICAL SOCIETY, vol. 155, no. 7, 2008, pages H496 - H503 |
REGIONAL ANESTHESIA,, vol. 16, no. 5, September 1991 (1991-09-01) - October 1991 (1991-10-01), pages 286 - 287 * |
SCIENCE, vol. 298, 2002, pages 402 - 406 |
ZHENGWEN LI; ANTTI RAHTU; ROY G. GORDON, JOURNAL OF THE ELECTROCHEMICAL SOCIETY, vol. 153, 2006, pages C787 - C794 |
ZHENGWEN LI; ROY G. GORDON, JOURNAL CHEMICAL VAPOR DEPOSITION, vol. 12, 2006, pages 435 - 441 |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017069672A1 (en) * | 2015-10-23 | 2017-04-27 | Isifer Ab | Composition for treatment of infertility in a female subject |
AU2016340769B2 (en) * | 2015-10-23 | 2018-07-12 | Isifer Ab | Composition for treatment of infertility in a female subject |
EA036687B1 (en) * | 2015-10-23 | 2020-12-08 | Исифер Аб | Composition for treatment of endometriosis related infertility in a female subject |
US11191839B2 (en) | 2015-10-23 | 2021-12-07 | Isifer Ab | Composition for treatment of infertility in a female subject |
Also Published As
Publication number | Publication date |
---|---|
AU774046B2 (en) | 2004-06-17 |
US6835388B2 (en) | 2004-12-28 |
NO20014361D0 (en) | 2001-09-07 |
US20030004213A1 (en) | 2003-01-02 |
US20030008916A1 (en) | 2003-01-09 |
CA2364470A1 (en) | 2000-09-14 |
NO20014361L (en) | 2001-11-02 |
ES2249250T3 (en) | 2006-04-01 |
EP1158978B1 (en) | 2005-10-05 |
NO323693B1 (en) | 2007-06-25 |
AU3363700A (en) | 2000-09-28 |
US6716446B2 (en) | 2004-04-06 |
EP1158978A1 (en) | 2001-12-05 |
ATE305784T1 (en) | 2005-10-15 |
EP1158978A4 (en) | 2004-03-17 |
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