FR2627386A1 - Compsns. for topical application to eyes - contg. colostrum lactoserum and vitamin=a - Google Patents

Abstract

Compositions for ocular administration contg. (I) colostrum lactoserum, and (II) 0.05-0.2% of vitamin A, its precursors, or its derivatives, are new. The lactoserum is usually diluted with physiological serum to a concn. of 10g total protein per litre. The compsns. may be in the form of eye drops, creams or gels and may also contain an antiseptic preservative such as sorbic acid. USE - Treatment of ocular dryness of any cause, the composition having a nutritive and regenerative action. Also useful in the treatment of corneal ulcers.

Description

 The invention relates to a composition for external use intended for ocular administration.

 The nutritive and healing activity of colostrum on the epithelia is known, for example from invention patent No. 79 17118, but the preparation eliminates the fat-soluble vitamins, including vitamin A.

 The present invention therefore relates to new compositions for external use based on colostrum whey of animal origin, associated with vitamin A, or with precursors or derivatives of this vitamin.

Colostrum and tears are external secretions and have a number of common properties the presence of an immune system common to all external secretions represented by non-specific antibacterial proteins, namely
- lactotransferrin, iron chelator, which deprives the environment of a
element necessary for the growth of most bacteria.

- lysozyme, which is a muramidase which attacks the wall of
Gram positive bacteria.

In colostrum, and not in tears, there is a powerful antimicrobial system: lactoperoxidase-thiocyanate, to which are added some minor antimicrobial factors, such as
- xanthine oxidase,
- ss lysine.

 In addition, colostrum contains an extremely large amount of immunoglobulins: in particular, the immunoglobulins G and the secretory immunoglobulins A which represent approximately 20% of the total proteins.

 All these elements are found in the colostrum whey, which differs from the colostrum itself by the absence of caseins which have been coagulated under the action of rennet.

 Figure 1 shows the electrophoretic curve of the colostrum.

 Diagram 2 shows the electrophoretic curve of the whey, on which two peaks corresponding to caseins are missing.

 Caseins are found in milk and colostrum - in the form of large micelles that unite the protein molecules. These micelles have a diameter of about 100 nanometers. The size and the importance of their surface make that they can be strongly antigenic and their elimination should allow a better tolerance and to avoid a certain number of allergic reactions.

 On the other hand, the elimination of approximately 20% of the proteins from the colostrum leads to a relative increase in the concentration of the active ingredients in the whey.

The main proteins in whey are
- b lactoglobulin,
- 1 'lactalbumin,
- serum albumin,
- immunoglobulins.

 Colostrum whey is extremely rich in amino acids since the average levels can be 30 g / l. We know that amino acids are the essential elements for the construction of cell materials and therefore for tissue nutrition. The ratio of essential amino acids for life to total amino acids is 3.2 in whey.

 Whey contains mineral salts and trace elements.

In addition, it contains numerous vitamins, water-soluble vitamins and some fat-soluble vitamins, the average concentration of which is provided by the table below.
Vitamins Average concentration
according to literature
Vitamin B1 19.00 Ug / l
Vitamin B2 302.00 ug / l
Vitamin B12 0.45 ug / l
vitamin C 72.00 mg / l
Vitamin E 14.80 Ug / l
Nicotinic acid 750.00 Ug / l
Pantothenic acid i, 83 mg / l
Biotin 0.60 mg / l
Folic acid 0.50 mg / l
It should be noted in this table the large amount of pantothenic acid as well as the presence of biotin which are factors allowing the development of skin tissue.

 As most of the fat-soluble vitamins have been eliminated by creaming and by coagulation with rennet, we suggest adding vitamin A, or its precursors or its derivatives, in order to complete the action of whey, vitamin A having an action on the differentiation and development of epithelial cells and on the secretion of mucus.

 The activity of colostrum on growth is extremely important since it is it that will allow the "start of the newborn". This activity is due to the presence of one or more growth factors ("epithelial growth factor") and to an extremely high level of insulin, a hundred times more than in serum - which makes it stimulates cell growth and is at the same time anabolic for the tissues.

 We also note in colostrum the presence of prolactin, about seven times more concentrated than in serum, and recent work has shown that prolactin could have an activity on the secretion of the lacrimal gland.

 Whey benefits from the same properties.

 The justification for the use of whey is based on the fact that during dry eyes, whatever the cause, the decrease in tears provokes a certain desiccation of the conjunctival epithelium. , the nutritive power of the tears being insufficient, trophic disorders will occur by lack of nutrition of the corneo-conjunctival epithelium. It is for this reason that we thought of supplementing the reduction or the disappearance of the lacrimal functions by the whey.

 Because of its nutritive activity and the growth factors it contains, whey can also be used in all ulcers of the cornea, whatever the etiology, and in particular in meta-herpetic ulcers which often do not heal neither spontaneously nor even with current healing treatments.

 The combination: whey and vitamin A, or the precursors or derivatives of this vitamin, is prepared in the form of eye drops or ointment or gel.

 The whey is centrifuged at 5,000 g for 10 minutes and the residue is discarded; the preparation is carried out from the supernatant. The total proteins of the supernatant whey are dosed and in the case of an eye drop, a dilution is made with physiological saline at 9 Zo to obtain the desired protein concentration, the pH and the osmolarity are adjusted to be compatible with those of the tears , a preservative is added. In the case of an ointment, the excipient may be lanolin or petrolatum. For a gel, the excipient may be the aerosil.

 Vitamin A (or its precursors or its derivatives) is added at a concentration preferably close to 0.1%, in a range of 0.05% to 0.2%.

The following examples are given without implied limitation to illustrate the invention
Example 1: preparation of eye drops
The bovine dairy whey is diluted in such a way as to obtain a concentration of 10 g / l of total protein, the resulting composition having a pH of 7.0 and an osmolarity of 305 nm compatible with those of tears. The composition is sterilized by passage through a filter or a membrane or by any other physical means, then preserved by lyophilization.

 Example 2: preparation of an eye drop according to Example 1, to which 0.1% of vitamin A, or of the precursors or derivatives of this vitamin, is added.

Claims (6)

 10 Composition for external use intended for ocular administration, characterized in that it contains colostrum whey as a selective principle, vitamin A or its precursors or its derivatives at a concentration of 0.05% to 0.2% .  20 Composition according to claim 1, characterized in that it is in the form of an eye drop.  30 Composition according to claim 2, characterized in that it consists of whey diluted with physiological serum.  40 Composition according to the preceding claims, characterized in that the whey is diluted to reach a concentration of 10 g of total protein per liter.  5 Composition according to claim 1, characterized in that the vitamin A, or its precursors or its derivatives, added is at a concentration close to 0.1%.  60 Composition according to claim 1, characterized in that it is in the form of an ointment or a gel.  70 Composition according to the preceding claims, characterized in that it also contains an antiseptic preservative.  .80 Composition according to the preceding claims, characterized in that the preservative is sorbic acid.