WO1991012026A1 - Means of reducing surgical adhesions - Google Patents
Means of reducing surgical adhesions Download PDFInfo
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- WO1991012026A1 WO1991012026A1 PCT/AU1991/000052 AU9100052W WO9112026A1 WO 1991012026 A1 WO1991012026 A1 WO 1991012026A1 AU 9100052 W AU9100052 W AU 9100052W WO 9112026 A1 WO9112026 A1 WO 9112026A1
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- phospholipid
- adhesions
- solution
- suspension
- rats
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-
- 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
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
Definitions
- the present invention relates to a method for reducing or preventing unwanted adhesions between tissue surfaces in both humans and animals after surgery or other trauma.
- Adhesions can also occur without surgery. However, it is not known what causes them to form and what prevents- them forming between adjacent tissue surfaces under normal physiological conditions. Among previous methods known to prevent surgical adhesions is the use of hyaluronic acid, which has resulted in modest improvements, or else by interposing a barrier along the fascial plane between the incisions, which is later removed by a subsequent incision in the skin. Alternatively, a barrier material which is eventually digested without an inflammatory reaction has been used. However, the barrier method has been found to be limited in its application.
- the present invention is therefore directed to a means of preventing surgical adhesions which is simple, safe, inexpensive and easy to apply.
- This invention is based upon the principle that the tissue "bridges" constituting surgical adhesions will not form if there is no physical adhesion between adjacent surfaces. If they form between surfaces that never move relative to each other, then their formation is unlikely to be manifest clinically. The task is therefore one of preventing the sticking of adjacent surfaces which normally slide over each other easily, since the formation of tissue "bridges", restricts movement, or causes pain or haemorrhaging.
- any barrier should have one or more of the following functions. It should act as a release agent to prevent sticking. It should act as a lubricant facilitating sliding of adjacent surfaces. This needs to be a boundary lubricant since any fluid could be squeezed out under load leaving direct solid-to-solid contact of the two tissue surfaces. It should provide a biological barrier.
- Phosphatidylcholine commonly known as lecithin, is a phosphatide found in all living organisms (plants and animals) . It is a constituent of biological membranes and is involved in permeability, oxidative phosphorylation, phagocytosis, and chemical and electrical excitation. Phosphatidylcholine has been identified in many animal tissues and organs such as the brain, nervous system, liver, heart, lungs, kidneys, blood, milk, sperm, in micro-organisms and throughout the vegetable kingdom.
- Lecithin is a mixture of the diglycerides of stearic, palmitic and oloeic acids linked to the choline ester of phosphoric acid and can be represented by the general formula I
- Rl and R2 are f tty acid residues. Usually one acid is saturated and the other unsaturated.
- Phosphatidylcholines are highly surface active as witnessed by “surfactants” in the lung.
- Application PCT/AU88/00322 discloses the ability of phosphatidylcholines to form sheets of molecules in parallel planes which can slide over each other providing very low coefficients of kinetic friction in the range 0.002-0.006 or lower. Moreover it could provide these values under a high
- the present invention therefore concerns a method for the reduction or prevention of unwanted surgical adhesion between two tissue surfaces in an animal including a human, which comprises interposing between said surfaces an effective amount of a phospholipid suspension or solution comprising a phospholipid and a sterile surgically acceptable carrier.
- Suitable phospholipids for use in the present invention are listed in Table 1, although other phospholipids can also be used. Mixtures or combinations of the phospholipids are also permissible.
- CDP diglyceride choline phosphoglycerides ethanolamine phosphoglycerides
- sphingomyelin ceramide phosphorylcholine
- ceramide phosphorylethanolamine
- ceramide phosphorylglycerol
- ceramide phosphorylglycerophosphate
- ceramide phosphorylinositol-containing lipids
- the phospholipid is phosphatidylcholine (lecithin).
- phospholipids such as phosphatidylethanolamines, phosphatidylinositols, phosphatidylserines, phosphatidylglycerides and sphingomyelin may also be used in admixture with the phosphatidylcholine.
- Phospholipids can be used alone, or together with other substances such as hyaluronic acid. Such mixtures have an advantage of an improved ability to stay in suspension. Further, there are advantages and synergism between the phospholipids and hyaluronic acid, in the performance of the invention, in some situations.
- the phospolypid can be combined with or dissolved in substances such as propylene glycol and related substances, provided they are non-toxic and suitable for application to organ and skin surfaces in surgery.
- the poor solubility of phospholipid, and especially DPPC and other phosphatidylcholines, may also be overcome by dispersing them using ultrasound, preferably in an aqueous solution of sodium hyaluronate, or in saline solution, for example.
- the purity of the phospholipid is normally 99%, however less pure phospholipid may also be used, since certain impurities may act synergistically, e.g. in phosphatidylcholine the impurities tend to be phosphatidylethanolamines, phosphatidylinostols, phosphatidylserines, phosphatidylglycerides and sphingomyelin.
- the phospholipid suspension of the invention may comprise a phospholipid dispersed in a neutralized solution of hyaluronic acid.
- concentration of the phospholipid suspension is preferably about 3 mg ml " of phospholipid disbursed in 10 mg ml "" of a neutralized solution of hyaluronic acid.
- the phospholipid may also be dispersed in a solution of sodium hyaluronate.
- the phospholipid can be dispersed by any suitable means, such as by ultrasound.
- the phospholipid may be dissolved in propylene glycol, (or similar non-toxic substances) and optionally further diluted with water. If desired hyaluronic acid of a salt of hyaluronic acid may also be included in this solutio .
- the phospholipid suspension or solution is in the form of a gel, paste or viscous solution to assist in its application to the tissue surfaces.
- the phospholipid suspension or solution may be applied and then re-applied at regular intervals after the first application.
- the phospholipid suspension is applied to the interface between the tissue surfaces of the surgical incision at the time of surgery, preferably with top-up doses administered by injection for up to 14 days afterwards.
- suspension or solution should not be applied to the tissue surfaces that are to be rejoined, and which are sutured together.
- the method of application may be by coating the surfaces by means of a brush, spray, or even manually. If the surgery permits, the organ or surface can be dipped in the solution or suspension of phospholipid. Any suitable method of application can be used.
- EXAMPLE 1 The prevention of absolute alcohol induced caecal adhesions in rats.
- a left flank laparotomy was conducted on 33 adult female Wistar rats under halothane anaesthesia (4% induction, 1% maintenance) .
- the surgical site was clipped and disinfected using alcoholic iodine.
- the caecum was exteriorized in all rats.
- the caecum was swabbed with absolute alcohol on each lateral surface and then treated as above with either saline, Hyaluronic Acid or Hyaluronic Acid plus phospholipid.
- the abdominal wall was closed with 4-0 Ethiflex (Ethicon) mattress sutures.
- the skin was then closed using subcuticular sutures (4-0 Ethiflex) and the wound treated with Neotracin and Nobecutane (Astra Pharmaceuticals).
- EXAMPLE 2 The prevention of mechanically induced caecal adhesions.
- a left flank laparotomy was conducted on 19 adult male Wistar rats as described in Example 1.
- mice Twenty adult male Wistar rats were injected intraperitoneally using an 18 gauge needle with 0.05ml/kg of a suspension of talc in saline (mg/ml w/v) .
- the rats were split into two groups of 10. One group received a second ip injection of 0.5 mls/kg saline while the other received a second ip injection of 0.5mls/kg of phospholipid and HA.
- the invention is intended for use in surgery as a method of preventing or reducing surgical adhesions in subjects.
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
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Abstract
A method of reducing surgical adhesions in a patient by means of coating the tissue surfaces with a phospholypid, preferably lecithin, in suspension or solution in an inert carrier, such as for example, water, saline, or propylene glycol, or mixtures thereof. Hyaluronic acid, or its salts, may also be present in the mixture.
Description
MEANS OF REDUCING SURGICAL ADHESIONS
TECHNICAL FIELD
The present invention relates to a method for reducing or preventing unwanted adhesions between tissue surfaces in both humans and animals after surgery or other trauma.
BACKGROUND ART
Most surgery involves an incision in the skin followed by further incisions into deeper tissue as needed. Upon completion, the two edges of each incision are held together by sutures or other means, to promote healing by enabling the cells at the open ends to proliferate and fuse together. A problem arises when tissue union not only occurs between the edges produced by this incision, but also between these edges and those of adjacent incisions. These fibrous unions can become vascularized to form tissue "bridges", which represent tight binding between two tissue surfaces which would otherwise slide over each other as easily-as they did before surgery. These tissue "bridges" are known as "surgical adhesions". They are most undesirable where they inhibit the relative movement of adjacent tissue surfaces and are often manifest as stiffness, or immobility. If motion is forced, surgical adhesions can result in pain or they may rupture to produce haemorrhage.
Repeat surgery seldom cures the problem because surgical adhesions usually reform in the same sites. Individuals vary greatly in their susceptibility and some tissues are more prone than others. Surgical adhesions are common in abdominal surgery but can occur unpredictably in almost any surgical procedure. Although deaths from abdominal surgery are rare, the major cause is surgical adhesions.
Adhesions can also occur without surgery. However, it is not known what causes them to form and what prevents- them forming between adjacent tissue surfaces under normal physiological conditions.
Among previous methods known to prevent surgical adhesions is the use of hyaluronic acid, which has resulted in modest improvements, or else by interposing a barrier along the fascial plane between the incisions, which is later removed by a subsequent incision in the skin. Alternatively, a barrier material which is eventually digested without an inflammatory reaction has been used. However, the barrier method has been found to be limited in its application.
It is an object of the present invention to provide an improved method of reducing surgical adhesions which will substantially overcome, or ameliorate, the abovementioned disadvantages. The present invention is therefore directed to a means of preventing surgical adhesions which is simple, safe, inexpensive and easy to apply.
DISCLOSURE OF THE INVENTION
This invention is based upon the principle that the tissue "bridges" constituting surgical adhesions will not form if there is no physical adhesion between adjacent surfaces. If they form between surfaces that never move relative to each other, then their formation is unlikely to be manifest clinically. The task is therefore one of preventing the sticking of adjacent surfaces which normally slide over each other easily, since the formation of tissue "bridges", restricts movement, or causes pain or haemorrhaging.
It is desirable that any barrier should have one or more of the following functions. It should act as a release agent to prevent sticking. It should act as a lubricant facilitating sliding of adjacent surfaces. This needs to be a boundary lubricant since any fluid could be squeezed out under load leaving direct solid-to-solid contact of the two tissue surfaces. It should provide a biological barrier.
Phosphatidylcholine, commonly known as lecithin, is a phosphatide found in all living organisms (plants and animals) . It is a constituent of biological membranes and is involved in permeability, oxidative phosphorylation, phagocytosis, and chemical and electrical excitation.
Phosphatidylcholine has been identified in many animal tissues and organs such as the brain, nervous system, liver, heart, lungs, kidneys, blood, milk, sperm, in micro-organisms and throughout the vegetable kingdom.
Lecithin is a mixture of the diglycerides of stearic, palmitic and oloeic acids linked to the choline ester of phosphoric acid and can be represented by the general formula I
CH2-OCOR1 CH-OCOR2
0-
CH2-OP -OCH2CH2N+(CH3)3
0 (I)
wherein Rl and R2 are f tty acid residues. Usually one acid is saturated and the other unsaturated.
Phosphatidylcholines are highly surface active as witnessed by "surfactants" in the lung. International Patent
Application PCT/AU88/00322 discloses the ability of phosphatidylcholines to form sheets of molecules in parallel planes which can slide over each other providing very low coefficients of kinetic friction in the range 0.002-0.006 or lower. Moreover it could provide these values under a high
2 load of up to 18 Kg/cm . The same phospholipid was also a good release agent, reducing the force of adhesion by at least
99%.
However it is completely unexpected that phospholypids act to prevent or reduce the occurrence of surgical adhesions.
The discovery that phospholipid applied to a traumatised tissue surface will ameliorate the formation of surgical adhesion has led to the present invention.
The present invention therefore concerns a method for the reduction or prevention of unwanted surgical adhesion between two tissue surfaces in an animal including a human, which comprises interposing between said surfaces an effective amount of a phospholipid suspension or solution comprising a
phospholipid and a sterile surgically acceptable carrier.
Suitable phospholipids for use in the present invention are listed in Table 1, although other phospholipids can also be used. Mixtures or combinations of the phospholipids are also permissible.
Table 1 PHOSPHOLIPIDS
Phosphoσlycerides
phosphatidic acids cytidylic phosphoglycerides (CDP diglyceride) choline phosphoglycerides ethanolamine phosphoglycerides
N-methylethanolamine phosphoglyceridesN,N-dimethylethanolamine phosphoglycerides
N-acylethanolamine phosphoglyceride serine phosphoglycerides
N-2-(hydroxyethyl)alanine phosphoglyceride glycerol phosphoglycerides glycerophosphate phosphoglycerides phosphatidylglycerol phosphoglyceride (diphosphatidylglycerol) mono and diacylglycerol phosphoglycerides (lysobisphosphatidic acids) glueosaminylglycerol phosphoglyceride 0-amino acid esters of glycerol phosphoglycerides inositol phosphoglyceride inositol monophosphate phosphoglyceride inositol diphosphate phosphoglyceride monomannosyl-hexamannosyl inositol phosphoglycerides glucose phosphoglyceride O-diglucosylglycerol phosphoglyceride
Phosphoσlycolipids
diacyl (glycerylphosphoryldiglucosyl) glycerol
Phosphodiol lipids
acyl dihydroxyacetone phosphate alkyl dihydroxyacetone phosphate
Phosphosphingolipids
sphingomyelin (ceramide phosphorylcholine) ceramide phosphorylethanolamine ceramide phosphorylglycerol ceramide phosphorylglycerophosphate ceramide phosphorylinositol-containing lipids
Preferably the phospholipid is phosphatidylcholine (lecithin). Further, other phospholipids such as phosphatidylethanolamines, phosphatidylinositols, phosphatidylserines, phosphatidylglycerides and sphingomyelin may also be used in admixture with the phosphatidylcholine.
Phospholipids can be used alone, or together with other substances such as hyaluronic acid. Such mixtures have an advantage of an improved ability to stay in suspension. Further, there are advantages and synergism between the phospholipids and hyaluronic acid, in the performance of the invention, in some situations.
In addition, the phospolypid can be combined with or dissolved in substances such as propylene glycol and related substances, provided they are non-toxic and suitable for application to organ and skin surfaces in surgery.
The poor solubility of phospholipid, and especially DPPC and other phosphatidylcholines, may also be overcome by dispersing them using ultrasound, preferably in an aqueous solution of sodium hyaluronate, or in saline solution, for example.
The purity of the phospholipid is normally 99%, however less pure phospholipid may also be used, since certain impurities may act synergistically, e.g. in phosphatidylcholine the impurities tend to be phosphatidylethanolamines, phosphatidylinostols, phosphatidylserines,
phosphatidylglycerides and sphingomyelin.
However, it is highly desirable to exclude certain impurities such as lysophosphatidylcholines. The levels of these impurities should preferably be kept below 0.1%.
The phospholipid suspension of the invention may comprise a phospholipid dispersed in a neutralized solution of hyaluronic acid. The concentration of the phospholipid suspension is preferably about 3 mg ml" of phospholipid disbursed in 10 mg ml"" of a neutralized solution of hyaluronic acid. The phospholipid may also be dispersed in a solution of sodium hyaluronate. The phospholipid can be dispersed by any suitable means, such as by ultrasound.
Alternatively, the phospholipid may be dissolved in propylene glycol, (or similar non-toxic substances) and optionally further diluted with water. If desired hyaluronic acid of a salt of hyaluronic acid may also be included in this solutio .
Preferably the phospholipid suspension or solution is in the form of a gel, paste or viscous solution to assist in its application to the tissue surfaces.
The phospholipid suspension or solution may be applied and then re-applied at regular intervals after the first application.
The phospholipid suspension is applied to the interface between the tissue surfaces of the surgical incision at the time of surgery, preferably with top-up doses administered by injection for up to 14 days afterwards.
Usually the suspension or solution should not be applied to the tissue surfaces that are to be rejoined, and which are sutured together.
The method of application may be by coating the surfaces by means of a brush, spray, or even manually. If the surgery permits, the organ or surface can be dipped in the solution or suspension of phospholipid. Any suitable method of application can be used.
MODES FOR CARRYING OUT THE INVENTION
The invention is now described with reference to some examples.
EXAMPLES
In the following Examples the prevention of absolute alcohol-induced caecal adhesions, mechanically induced caecal adhesions and talc-induced adhesions were demonstrated on istar rats.
The incidence of adhesions was scored on a scale of 0-4 as below.
0 - no adhesions present
1 - thin filmy, easily separated adhesions
2 - vascularized but separable adhesions
3 - moderate vascularized, adhesions
4 - grossly disseminated inseparable adhesions
EXAMPLE 1 - The prevention of absolute alcohol induced caecal adhesions in rats.
A left flank laparotomy was conducted on 33 adult female Wistar rats under halothane anaesthesia (4% induction, 1% maintenance) .
The surgical site was clipped and disinfected using alcoholic iodine. The caecum was exteriorized in all rats.
In 10 rats, 1ml of saline was applied to each lateral surface and a further 1ml of saline was instilled into the peritoneal cavity upon return of the caecum.
In the remaining 23 rats, the caecum was swabbed with absolute alcohol on each lateral surface and then treated as above with either saline, Hyaluronic Acid or Hyaluronic Acid plus phospholipid.
The abdominal wall was closed with 4-0 Ethiflex (Ethicon) mattress sutures. The skin was then closed using subcuticular sutures (4-0 Ethiflex) and the wound treated with Neotracin and Nobecutane (Astra Pharmaceuticals).
Food intake was monitored for fourteen days to ensure adequate recovery. After fourteen days the animals were
sacrificed -by CO~ inhalation and cervical dislocation.
♦significantly different from the alcohol control (P<0.05).
The saline treated control rats showed no adhesions, whereas alcohol treated rats, showed substantial adhesions.
The addition of HA to the alcohol treated rats showed no significant effect on the incidence of adhesions.
However, the addition of both HA and phospholipid to the alcohol treated rats significantly reduced the formation of adhesion by 39% (P<0.025).
EXAMPLE 2 - The prevention of mechanically induced caecal adhesions.
A left flank laparotomy was conducted on 19 adult male Wistar rats as described in Example 1.
However, instead of swabbing the caecum with alcohol, it was abrasively swabbed with a dry surgical swab until noticeable hyperaemia was present. They were then treated with either saline or HA and phospholipid as in Example 1.
After 14 days the rats were sacrificed.
RESULTS Treatment No. of rats Adhesion scores
Saline 10 1.5 ± 0.27 HA + PL 9 0.56 + 0.18*
♦significantly different from saline control (P<0.01)
The rats treated with phospholipid and HA showed a significant decrease in the formation of adhesion by 63% (P<0.025).
EXAMPLE 3 - The prevention of talc induced adhesions.
Twenty adult male Wistar rats were injected intraperitoneally using an 18 gauge needle with 0.05ml/kg of a suspension of talc in saline (mg/ml w/v) . The rats were split into two groups of 10. One group received a second ip injection of 0.5 mls/kg saline while the other received a second ip injection of 0.5mls/kg of phospholipid and HA.
After 14 days the rats were sacrificed by cervical dislocation.
RESULTS Treatment No. of rats Adhesion scores
Talc + Saline 5 3.4 ± 0.24
Talc + PL 5 2.6 + 0.4
The addition of talc to the rats caused substantial formation of adhesions.
The addition of phospholipid to the rats significantly reduced the formation of adhesion by 24%. However, when the rats received an additional injection of saline or phospholipid and HA, no significant effect on the incidence on these adhesions was noted.
INDUSTRIAL APPLICABILITY
The invention is intended for use in surgery as a method of preventing or reducing surgical adhesions in subjects.
The foregoing describes only some of the embodiments of the present invention and modifications, obvious to those skilled in the art, can be made thereto without departing from the scope of the present invention.
Claims
1. A method for the reduction or prevention of unwanted surgical adhesions between two tissue surfaces in an animal, including a human, having undergone surgery or similar trauma, which comprises interposing between said surfaces an effective amount of a phospholipid in suspension or solution in a surgically acceptable carrier.
2. The method of claim 1 wherein the suspension or solution also includes hyaluronic acid or a surgically acceptable salt thereof.
3. The method of claim 1 wherein the carrier is water and/or propylene glycol.
4. The method claim 1 wherein the phospholipid is 99% pure phosphatidylcholine.
5. The method of claim 1 wherein the solution or suspension is in the form of a gel, paste or viscous solution.
6. A viscous solution of a phospholipid, propylene glycol and water for use to prevent or reduce surgical adhesions in a patient having undergone trauma or surgery.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AUPJ8629 | 1990-02-14 | ||
AUPJ862990 | 1990-02-14 |
Publications (1)
Publication Number | Publication Date |
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WO1991012026A1 true WO1991012026A1 (en) | 1991-08-22 |
Family
ID=3774498
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/AU1991/000052 WO1991012026A1 (en) | 1990-02-14 | 1991-02-14 | Means of reducing surgical adhesions |
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Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5610148A (en) * | 1991-01-18 | 1997-03-11 | University College London | Macroscopically oriented cell adhesion protein for wound treatment |
EP0868190A1 (en) * | 1995-12-19 | 1998-10-07 | MacNaught Medical Pty. Limited | Phospholipid and propylene glycol based lubricant |
WO1999003481A1 (en) * | 1997-07-14 | 1999-01-28 | Stig Bengmark | Compositions for lubricating and separating tissues and biological membranes |
GB2335853A (en) * | 1998-04-03 | 1999-10-06 | Britannia Pharmaceuticals Ltd | Inhibition of Surgical Adhesions |
WO2003000344A1 (en) * | 2001-06-25 | 2003-01-03 | Britannia Pharmaceuticals Limited | Use of phospholipids for the prevention 0f surgical adhesions |
WO2003082245A1 (en) * | 2002-04-03 | 2003-10-09 | Lamellar Therapeutics Limited | Methods of using lamellar bodies for therapeutic purposes |
CN101959896A (en) * | 2008-03-04 | 2011-01-26 | 大不列颠药品有限公司 | Crystalline phospholipid, method for its production and use in treating damaged tissue |
US9173901B2 (en) | 2003-09-25 | 2015-11-03 | Lamellar Therapeutics Limited | Compositions and methods of using lamellar bodies for modifying linear biological macromolecules |
CN107920994A (en) * | 2015-06-23 | 2018-04-17 | 板层小体生物医学有限公司 | The composition and method of lamellar body for therapeutic purposes |
US20180147262A1 (en) * | 2015-04-30 | 2018-05-31 | University Of Bremen | Novel skin medical and cosmetic care product |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU6570986A (en) * | 1985-11-27 | 1987-06-04 | Ethicon Inc. | Method for inhibiting post-surgical adhesion formation by the topical administration of non-steroidal anti- inflammatory drug |
AU2320888A (en) * | 1987-08-25 | 1989-03-31 | Macnaught Pty Limited | Hyaluronic acid lubricating compounds |
-
1991
- 1991-02-14 WO PCT/AU1991/000052 patent/WO1991012026A1/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU6570986A (en) * | 1985-11-27 | 1987-06-04 | Ethicon Inc. | Method for inhibiting post-surgical adhesion formation by the topical administration of non-steroidal anti- inflammatory drug |
AU2320888A (en) * | 1987-08-25 | 1989-03-31 | Macnaught Pty Limited | Hyaluronic acid lubricating compounds |
Cited By (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5610148A (en) * | 1991-01-18 | 1997-03-11 | University College London | Macroscopically oriented cell adhesion protein for wound treatment |
EP0868190A1 (en) * | 1995-12-19 | 1998-10-07 | MacNaught Medical Pty. Limited | Phospholipid and propylene glycol based lubricant |
EP0868190A4 (en) * | 1995-12-19 | 2001-02-14 | Macnaught Med Pty Ltd | Phospholipid and propylene glycol based lubricant |
WO1999003481A1 (en) * | 1997-07-14 | 1999-01-28 | Stig Bengmark | Compositions for lubricating and separating tissues and biological membranes |
AU738149B2 (en) * | 1997-07-14 | 2001-09-13 | Stig Bengmark | Compositions for lubricating and separating tissues and biological membranes |
US6719960B1 (en) | 1998-04-03 | 2004-04-13 | Britannia Pharmaceuticals Ltd. | Use of phospholipids for the manufacture of a medicament for the prevention of adhesions |
GB2335853A (en) * | 1998-04-03 | 1999-10-06 | Britannia Pharmaceuticals Ltd | Inhibition of Surgical Adhesions |
WO1999051244A1 (en) * | 1998-04-03 | 1999-10-14 | Britannia Pharmaceuticals Limited | Use of phospholipids for the manufacture of a medicament for the prevention of adhesions |
WO2003000344A1 (en) * | 2001-06-25 | 2003-01-03 | Britannia Pharmaceuticals Limited | Use of phospholipids for the prevention 0f surgical adhesions |
WO2003082245A1 (en) * | 2002-04-03 | 2003-10-09 | Lamellar Therapeutics Limited | Methods of using lamellar bodies for therapeutic purposes |
JP2005526101A (en) * | 2002-04-03 | 2005-09-02 | ラメラー セラピューティクス リミテッド | How to use lamellar body suitable for treatment |
EP2177212A1 (en) * | 2002-04-03 | 2010-04-21 | Lamellar Biomedical Limited | Methods of using lamellar bodies for therapeutic purposes |
US7906139B2 (en) | 2002-04-03 | 2011-03-15 | Lamellar Therapeutics Limited | Compositions and methods of using lamellar bodies for therapeutic purposes |
JP4657608B2 (en) * | 2002-04-03 | 2011-03-23 | ラメラー バイオメディカル リミテッド | Use of lamellar bodies in pharmaceutical compositions and drug formulations |
US9173901B2 (en) | 2003-09-25 | 2015-11-03 | Lamellar Therapeutics Limited | Compositions and methods of using lamellar bodies for modifying linear biological macromolecules |
US9750766B2 (en) | 2003-09-25 | 2017-09-05 | Lamellar Biomedical Limited | Compositions and methods of using lamellar bodies for modifying linear biological macromolecules |
CN101959896A (en) * | 2008-03-04 | 2011-01-26 | 大不列颠药品有限公司 | Crystalline phospholipid, method for its production and use in treating damaged tissue |
US20180147262A1 (en) * | 2015-04-30 | 2018-05-31 | University Of Bremen | Novel skin medical and cosmetic care product |
CN107920994A (en) * | 2015-06-23 | 2018-04-17 | 板层小体生物医学有限公司 | The composition and method of lamellar body for therapeutic purposes |
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