EP0289587A4 - Method for inducing vaginal lubrication - Google Patents
Method for inducing vaginal lubricationInfo
- Publication number
- EP0289587A4 EP0289587A4 EP19880900052 EP88900052A EP0289587A4 EP 0289587 A4 EP0289587 A4 EP 0289587A4 EP 19880900052 EP19880900052 EP 19880900052 EP 88900052 A EP88900052 A EP 88900052A EP 0289587 A4 EP0289587 A4 EP 0289587A4
- Authority
- EP
- European Patent Office
- Prior art keywords
- vip
- vaginal
- administration
- solution
- female
- 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.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2278—Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
Definitions
- the present invention relates to the neuropeptide, vasoactive intestinal peptide. More particularly, the invention concerns the induction of vaginal lubrication by administration of the peptide.
- Vasoactive intestinal peptide hereinafter referred to as VIP, is a 28-amino acid, carboxy-ter inal-amidated neuropeptide of animals, including fish, birds and mammals.
- the amino acid sequences of the VIP s of numerous species, including human, are known.
- the sequence of human VIP is identical to that of bovine, porcine and rat VIPs.
- VIP is known to be involved in neurotrans ission associated with vasodilation, smooth muscle relaxation, and secretion in a number of tissues. VIP has also been implicated in various physiological processes related to sexual arousal. Systemic administration of VIP to females has been found to decrease uterine smooth muscle activity and increase vaginal blood flow. Ottesen et al., Eur. J. Clin. Invest. 13, 321-324 (1983).
- vaginal lubricatory activity i.e., secretion of fluids from the vaginal wall into the vaginal cavity resulting in vaginal lubrication
- certain diseases such as diabetes, which involve atherosclerosis or neuropathy.
- Vaginal lubrication normally occurs during sexual arousal, and insufficient vaginal lubricatory activity can result in pain during sexual intercourse and generally unsatisfactory sexual relations.
- Our invention thus provides methods for protecting against bacterial, fungal and other infections of the genital tract of a female associated with insufficient vaginal lubricatory activity.
- the invention further provides methods for increasing vaginal lubrication in a female during sexual arousal and intercourse.
- application of the methods of the invention to increase vaginal lubrication during sexual arousal or intercourse results in reduction of pain during intercourse and, associated therewith, generally improved sexual relations.
- the present invention entails a method for inducing vaginal lubricatory activity in a female, which comprises administering to said female an amount of a vasoactive intestinal peptide effective to induce vaginal lubricatory activity.
- the invention entails also compositions for carrying out the method of the invention.
- the invention is preferably applied to human females, although it can also be applied to females of other mammalian species, such as bovine, canine, equine, ovine and porcine females.
- the preferred vasoactive intestinal peptide for use in the method of the invention is the carboxy- terminal-amidated VIP of the species to which the neuropeptide is to be administered.
- VIP's may also be employed, such as the VIP of a species other than the species to which the neuropeptide is to be administered.
- the VIP's for use in the method of the present invention are known and readily available in highly purified form.
- Administration of the VIP in accordance with the method of the invention can be systemic or local.
- Systemic administration is preferably by intravenous injection, although intraperitoneal, intramuscular or subcutaneous injection can also be employed. Continuous infusion may be used.
- Local administration is preferably to a portion of the wall of the female genital tract, most preferably to a portion of the inner wall of the vagina (i.e., the wall which defines the vaginal cavity) .
- Local administration can be accomplished by release of VIP by diffusion from a solution dispersed in a suitable support, such as a porous tampon or a suppository made with a composition comprising oleaginous base materials, or a suitable composition, such as an emulsion, cream, jelly, or tablet, placed in the vaginal cavity and in contact with the inner wall thereof.
- a suitable support such as a porous tampon or a suppository made with a composition comprising oleaginous base materials, or a suitable composition, such as an emulsion, cream, jelly, or tablet
- local administration can be by deposit of a volume of between about 1 ml and about 10 ml of a VIP-containing solution into the vaginal cavity in a manner whereby at least a portion of the vaginal wall is contacted with the solution.
- VIP a volume of solution into the vagina using an applicator such as one used to self-administer contraceptive foam.
- the VIP will be administered as part of a physiologically acceptable composition.
- compositions especially suitable for systemic administration, can be a solution comprising the VIP dissolved in a physiologically acceptable medium, such as physiological saline or phosphate-buffered saline, which may optionally include other physiologically acceptable substances, such as human serum albumin or the like, at physiologically acceptable concentrations, as understood in the art.
- a physiologically acceptable medium such as physiological saline or phosphate-buffered saline, which may optionally include other physiologically acceptable substances, such as human serum albumin or the like, at physiologically acceptable concentrations, as understood in the art.
- compositions more suitable for local administration can also be formulated by the skilled in the art. See, e. g., Okada et al., J. Pharmaceut. Sci. 71, 1367 - 1371 (1982) and 72, 75 - 78 (1983).
- Such compositions include those comprising, optionally dispersed in a suppository or cream of physiologically rm/r acceptable oleaginous substances (e.g., WITEPSOL-SS ⁇ 4 -" sold by Dynamit Nobel AG, W.
- the VIP in an aqueous solution that is approximately isotonic with physiological saline, has a pH of about 2.5 to about 4.5, and comprises human serum albumin or the like (Preferably peptidase free) at about 0.01 - 1.0 %, a protease inhibitor such as aprotinin (e.g., sold as TrasylolTM by Bayer A. G. , Leverkusen, W.
- aprotinin e.g., sold as TrasylolTM by Bayer A. G. , Leverkusen, W.
- the concentration of the VIP in the physiologically acceptable solution will be between about 0.1 ⁇ g and about 100 ⁇ g per ml. As the skilled will understand, the concentration will depend on the route of administration (e.g., local or intravenous), the total dose to be administered, and the time period over which the administration is to occur.
- a solution is prepared by simply dissolving under sterile conditions the purified, sterile VIP, to the desired concentration in sterilized, physiological acceptable medium. Then, if the solution is to be dispersed in a tampon, suppository, cream, jelly or the like to make a composition for local administration, the solution is combined with the desired substance, also under sterile conditions.
- the solution or other composition can be prepared at any time prior to use, including immediately prior thereto. If prepared more than a few hours prior to use, the solution may include physiologically acceptable, non-irritant preservatives, such as about 0.1% benzalkonium chloride.
- solution, or composition for local application if prepared more than a few hours prior to use, is preferably maintained at low temperature, preferably about 0 "C to about 4 ⁇ C.
- the dosage of VIP to be administered, and the rate of administration, will depend on the species, age, weight, and medical condition of the female to whom the neuropeptide is being administered, the route of administration, and the purpose of the administration.
- a single intravenous injection of about 1 ⁇ g to about 100 ⁇ g (about 0.01 ⁇ g/kg body weight to about 1 ⁇ g/kg body weight) of VIP in 1 ml to 10 ml of solution may be administered between about 10 minutes and 1 minute prior to intercourse or a volume of between about 1 ml and 10 ml of solution, or solution-containing composition, with between about 10 ⁇ g and l mg of VIP may be delivered into the vaginal cavity, to bathe the inner vaginal wall, between about 10 minutes and about 1 minute prior to intercourse.
- a continuous mode of administration may be employed. Suitable continuous modes of administration include continuous intravenous administration; percutaneous administration, as from a skin patch perfused with VIP in a physiologically acceptable carrier and applied to a body part suitable for absorption from the patch into the blood stream; or vaginal administration, as from a tampon or suppository perfused with a VIP solution and inserted into the vaginal cavity.
- the rate of administration will be between about 10 ⁇ 7 gram and 10" "5 gram per kilogram body weight per hour over periods ranging from about
- VIP be administered in accordance with the invention under the guidance of a physician or veterinarian.
- the dosage, route and rate of administration of the VIP will be determined by the physician or veterinarian, taking into account the above-described factors (species, age, weight, degree of impairment (if any) of vaginal lubricatory activity, medical condition, purpose for administration of the VIP) as well as the known effects of the VIP on vasodilation, blood pressure, pulse rate and the like.
- concentrations of the neuropeptide in peripheral blood plasma in excess of 1 microgram per liter should be avoided due to the known effects of neuropeptide on the cardiovascular system.
- EXAMP.LE I Fourteen women (age 22-39 years, weight 55-65 kg, 0-4 pregnancies and 0-3 deliveries) , who were receiving no medication, including oral contraceptives and intrauterine devices, volunteered for the study. The experiments were performed between the seventh and the sixteenth day of menstrual cycle, to insure that the measurements were made at the same time in the cycle for all of the women and that the women were not pregnant.
- vaginal transudate was measured by means of preweighed circular filter papers (12 mm diameter) arranged in layer and held inside a plastic suction capsule and in direct contact with the vaginal wall. Contact with the vaginal surface was assured with a light vacuum (20-30 mm Hg) . The area of vaginal surface from which fluid was collected was 1.13 cm 2 . The quantity of vaginal fluid was calculated from the weight gain of the filter papers during a certain period of time. Fresh filter papers and the suction capsule were applied every 30 minutes and weighed immediately after removal. Fluid released was, thus, measured during the period of infusion of VIP, during the 30 minutes immediately prior to the 30 minutes of infusion of the VIP, and during two successive 30 minute periods immediately after the infusion of the VIP.
- the median peripheral blood plasma concentration of VIP during saline infusion prior to infusion of VIP was 22-23 pmol/1.
- the median peripheral blood plasma concentration had increased to 200 pmol/1 (interquartile range: 130-240 pmol/1) ;
- the median peripheral plasma concentration reached 290 pmol/1 (interquartile range: 190-380 pmol/1) ;
- the median peripheral plasma concentration was 190 pmol/1 (interquartile range: 170-400 pmol/1) .
- vaginal lubricatory activity as measured by the rate of transudation of fluid to the inner vaginal wall, was increased by a factor of about 2 to 3.
- vaginal transudate induced by VIP as described here corresponds approximately to the amount produced on the inner vaginal surface during sexual self-stimulation to orgasm.
- test subjects in the present study reported that they felt the increase in heat rate and warmth, due to increased vaginal blood flow; but none of the subjects reported any sexual arousal.
- EXAMPLE II The effect of administration of VIP sub- epithelially to the inner wall of the vagina was studied as follows with 6 human volunteers.
- the volunteers ranged in age from 20 - 35 years, weighed 52 - 62 kg, had 0 - 3 pregnancies and 0 - 2 deliveries, and were receiving no medication, including oral contraceptives and intrauterine devices. With each volunteer, the experiment was performed between the seventh and sixteeenth day of the menstrual cycle. The volunteers had given written, informed consent after the study was approved by the local ethical committee of Copenhagen, Denmark.
- a measuring electrode was posi- tioned on the front wall of the vagina, about 5 cm up, to measure change in blood flow to the vagina.
- 0.2 ml of sterilized physiological saline, warmed to 37 ⁇ C was injected subepithelially at a depth of 2 mm at a site on the front wall of the vagina, about 3 cm up. 30 minutes after the injection of the saline solution, 0.2 ml of sterilized physiological saline containing 10 ⁇ g of filter-sterilized human VIP, also warmed to 37 ⁇ C, was injected subepithelially at a depth of 2 mm at about the same site as the injection of the saline without VIP.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Vascular Medicine (AREA)
- Reproductive Health (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Lubricants (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US93206986A | 1986-11-18 | 1986-11-18 | |
US932069 | 1986-11-18 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0289587A1 EP0289587A1 (en) | 1988-11-09 |
EP0289587A4 true EP0289587A4 (en) | 1990-12-05 |
Family
ID=25461718
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP19880900052 Withdrawn EP0289587A4 (en) | 1986-11-18 | 1987-11-18 | Method for inducing vaginal lubrication |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0289587A4 (en) |
JP (1) | JPH01501937A (en) |
AU (1) | AU609765B2 (en) |
WO (1) | WO1988003928A1 (en) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5958881A (en) * | 1991-04-25 | 1999-09-28 | Korman; Louis Y. | Composition containing VIP for injection and a method of enhancing visualization of tissues during medical procedures |
ES2162616T3 (en) * | 1991-04-25 | 2002-01-01 | Louis Y Korman | USE OF THE VASOACTIVE INTESTINAL PEPTIDE (VIP) TO INDUCE THE PARALYSIS OF THE GASTROINTESTINAL TRACT. |
US6949067B1 (en) | 2004-05-11 | 2005-09-27 | Dann Jeffrey A | Device and method for enhancing female sexual stimulation |
US8147399B2 (en) | 2004-05-11 | 2012-04-03 | Gloth David A | Device and method for applying a biocompatible substance to a female stimulation device |
CN1993137B (en) * | 2004-06-11 | 2015-04-22 | 维克特斯生物系统有限公司 | Compositions and methods for treatment of cardiovascular disease |
CN102205152A (en) * | 2011-05-25 | 2011-10-05 | 青岛明药堂医药科技开发有限公司 | Human body lubricant and preparation method thereof |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4221769A (en) * | 1972-11-08 | 1980-09-09 | Fisons Limited | Process for preventing the formation of calcium sulphate scale |
US4211769A (en) * | 1977-08-24 | 1980-07-08 | Takeda Chemical Industries, Ltd. | Preparations for vaginal administration |
US4220642A (en) * | 1978-09-07 | 1980-09-02 | Viktor Mutt | Vasoactive lung polypeptides |
US4551148A (en) * | 1982-09-07 | 1985-11-05 | Kv Pharmaceutical Company | Vaginal delivery systems and their methods of preparation and use |
-
1987
- 1987-11-18 EP EP19880900052 patent/EP0289587A4/en not_active Withdrawn
- 1987-11-18 WO PCT/US1987/003038 patent/WO1988003928A1/en not_active Application Discontinuation
- 1987-11-18 AU AU10417/88A patent/AU609765B2/en not_active Ceased
- 1987-11-18 JP JP63500461A patent/JPH01501937A/en active Pending
Non-Patent Citations (6)
Title |
---|
AM. J. OBSTET. GYNECOL., vol. 143, 1982, pages 414-420, The C.V. Mosby Co.; B. OTTESEN et al.: "Vasoactive intestinal polypeptide and the female genital tract: Relationship to reproductive phase and delivery" * |
MEDICAL ASPECTS OF HUMAN SEXUALITY, vol. 12, no. 8, 1978, pages 58-71; "Inadequate vaginal lubrication" * |
OBSTET GYNECOL., vol. 56, no. 5, November 1980, pages 621-624; G. WAGNER: "Vaginal blood flow during sexual stimulation" * |
PEPTIDES, vol. 8, no. 5, 1987, pages 797-800, Pergamon Journals Ltd, US; B. OTTESEN et al.: "Vasoactive intestinal polypeptide (VIP) provokes vaginal lubrication in normal women" * |
REGULARITY PEPTIDES, vol. 16, 1986, pages 299-304, Elsevier Publishers B.V. (Biomedical Division); B. OTTESEN et al.: "Effect of vasoactive intestinal polypeptide (VIP) on steroidogenesis in women" * |
See also references of WO8803928A1 * |
Also Published As
Publication number | Publication date |
---|---|
JPH01501937A (en) | 1989-07-06 |
WO1988003928A1 (en) | 1988-06-02 |
AU1041788A (en) | 1988-06-16 |
EP0289587A1 (en) | 1988-11-09 |
AU609765B2 (en) | 1991-05-09 |
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